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非ST上昇型心筋梗塞

著者: 宮内克己 順天堂大学 循環器内科

監修: 代田浩之 順天堂大学大学院医学研究科循環器内科学

著者校正/監修レビュー済:2018/02/28
患者向け説明資料

概要・推奨   

疾患のポイント:
  1. 非ST上昇型心筋梗塞とは、不安定プラークの破綻あるいは血管のびらんに血栓形成が生じ冠動脈の内腔閉塞を来す急性冠症候群(ACS)の1病態であり、心電図上はSTの持続的上昇を示さないが、心筋に障害を認め心筋逸脱酵素であるトロポニンT、トロポニンIあるいはCPK、CPK-MBの上昇を認める状態である。症状としては20分以上継続する胸痛を認めることが多い。また、心電図はST低下あるいはT波の陰転化等を認めることもあるが変化のないこともある。
  1. 非ST上昇型心筋梗塞の評価方法にトロポニンが加わり、頻度は増加傾向にある。なお、、の対応については別項を参考にしてほしい。
 
診断:
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
宮内克己 : 未申告[2021年]
監修:代田浩之 : 未申告[2021年]

編集部編集コンテンツ:
 
関連する医療事故:
  1. 手術前の患者で、心電図異常などあれば、術前に必ず循環器内科による評価を行う:
  1. 事例:術前検査を施行、心電図にて心筋梗塞の疑いありとのコメントおよび異常を気付いた。しかし、採血上は心筋逸脱酵素の上昇は認めず、自覚症状のなかった。入院翌日も予定通り局所麻酔下で約1時間の緑内障濾過手術を行った。術後3日目、努力様呼吸が認められ、精査で心室中隔破裂および冠動脈3枝病変を認め、状態改善せず死亡に至った。(詳細情報ページ:医療事故情報 詳細表示
  1. 吐き気を認める患者の鑑別に心筋梗塞を入れる:
  1. 事例:吐き気を訴えた患者をウイルス性腸炎と診断。整腸剤などを処方されたが病状は改善せず、翌27日朝、急性心筋梗塞で死亡となった。遺族が訴訟。(詳細情報ページ:医療事故情報 詳細表示

病態・疫学・診察

疾患情報  
  1. 非ST上昇型心筋梗塞とは、不安定プラークの破綻あるいは血管のびらんに血栓形成が生じた結果、冠動脈の内腔閉塞を来す急性冠症候群(ACS)の1種類の病態であり、心電図上はSTの持続的上昇を示さないものの、心筋に障害を認め心筋逸脱酵素であるトロポニンT、トロポニンIあるいはCPK、CPK-MBの上昇を認める疾患である。症状としては胸痛は20分以上継続することが多い。また、心電図はST低下あるいはT波の陰転化等を認めることもあるが変化のないこともある。
  1. 評価方法にトロポニンが加わり、頻度は増加傾向にある。
問診・診察のポイント  
症状:
  1. 急性冠症候群の典型的な症状は、正中部位または胸骨背面の局在の不明な胸部圧迫感・胸部絞扼感であるが、放散痛としては上腕、背中、頚、のど、歯、後頭部などでも起こりうる。冠動脈疾患のリスクを認める患者が横隔膜より上の痛みを認める場合では、特に虚血性心疾患の可能性を想定するとよい。また、狭心症の胸痛は労作により悪化し、持続時間は数分以内であることが多く、労作の中止後・硝酸薬を投与後は1~2分で改善をすることが多く、30分以上継続する場合は心筋梗塞を想定する。

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文献 

著者: J G Canto, M G Shlipak, W J Rogers, J A Malmgren, P D Frederick, C T Lambrew, J P Ornato, H V Barron, C I Kiefe
雑誌名: JAMA. 2000 Jun 28;283(24):3223-9.
Abstract/Text CONTEXT: Although chest pain is widely considered a key symptom in the diagnosis of myocardial infarction (MI), not all patients with MI present with chest pain. The extent to which this phenomenon occurs is largely unknown.
OBJECTIVES: To determine the frequency with which patients with MI present without chest pain and to examine their subsequent management and outcome.
DESIGN: Prospective observational study.
SETTING AND PATIENTS: A total of 434,877 patients with confirmed MI enrolled June 1994 to March 1998 in the National Registry of Myocardial Infarction 2, which includes 1674 hospitals in the United States.
MAIN OUTCOME MEASURES: Prevalence of presentation without chest pain; clinical characteristics, treatment, and mortality among MI patients without chest pain vs those with chest pain.
RESULTS: Of all patients diagnosed as having MI, 142,445 (33%) did not have chest pain on presentation to the hospital. This group of MI patients was, on average, 7 years older than those with chest pain (74.2 vs 66.9 years), with a higher proportion of women (49.0% vs 38.0%) and patients with diabetes mellitus (32.6% vs 25. 4%) or prior heart failure (26.4% vs 12.3%). Also, MI patients without chest pain had a longer delay before hospital presentation (mean, 7.9 vs 5.3 hours), were less likely to be diagnosed as having confirmed MI at the time of admission (22.2% vs 50.3%), and were less likely to receive thrombolysis or primary angioplasty (25.3% vs 74.0%), aspirin (60.4% vs 84.5%), beta-blockers (28.0% vs 48.0%), or heparin (53.4% vs 83.2%). Myocardial infarction patients without chest pain had a 23.3% in-hospital mortality rate compared with 9.3% among patients with chest pain (adjusted odds ratio for mortality, 2. 21 [95% confidence interval, 2.17-2.26]).
CONCLUSIONS: Our results suggest that patients without chest pain on presentation represent a large segment of the MI population and are at increased risk for delays in seeking medical attention, less aggressive treatments, and in-hospital mortality. JAMA. 2000;283:3223-3229

PMID 10866870  JAMA. 2000 Jun 28;283(24):3223-9.
著者: Maria Rubini Gimenez, Miriam Reiter, Raphael Twerenbold, Tobias Reichlin, Karin Wildi, Philip Haaf, Katharina Wicki, Christa Zellweger, Rebeca Hoeller, Berit Moehring, Seoung Mann Sou, Mira Mueller, Kris Denhaerynck, Bernadette Meller, Fabio Stallone, Sarah Henseler, Stefano Bassetti, Nicolas Geigy, Stefan Osswald, Christian Mueller
雑誌名: JAMA Intern Med. 2014 Feb 1;174(2):241-9. doi: 10.1001/jamainternmed.2013.12199.
Abstract/Text IMPORTANCE: Whether sex-specific chest pain characteristics (CPCs) would allow physicians in the emergency department to differentiate women with acute myocardial infarction (AMI) from women with other causes of acute chest pain more accurately remains unknown. OBJECTIVE To improve the management of suspected AMI in women by exploring sex-specific CPCs.
DESIGN, SETTING, AND PARTICIPANTS: From April 21, 2006, through August 12, 2012, we enrolled 2475 consecutive patients (796 women and 1679 men) presenting with acute chest pain to 9 emergency departments in a prospective multicenter study. The final diagnosis of AMI was adjudicated by 2 independent cardiologists.
INTERVENTIONS: Treatment of AMI in the emergency department.
MAIN OUTCOMES AND MEASURES: Sex-specific diagnostic performance of 34 predefined and uniformly recorded CPCs in the early diagnosis of AMI.
RESULTS: Acute myocardial infarction was the adjudicated final diagnosis in 143 women (18.0%) and 369 men (22.0%). Although most CPCs were reported with similar frequency in women and men, several CPCs were reported more frequently in women (P < .05). The accuracy of most CPCs in the diagnosis of AMI was low in women and men, with likelihood ratios close to 1. Thirty-one of 34 CPCs (91.2%) showed similar likelihood ratios for the diagnosis of AMI in women and men, and only 3 CPCs (8.8%) seemed to have a sex-specific diagnostic performance with P < .05 for interaction. These CPCs were related to pain duration (2-30 and >30 minutes) and dynamics (decreasing pain intensity). However, because their likelihood ratios were close to 1, the 3 CPCs did not seem clinically helpful. Similar results were obtained when examining combinations of CPCs (all interactions, P ≥ .05).
CONCLUSIONS AND RELEVANCE: Differences in the sex-specific diagnostic performance of CPCs are small and do not seem to support the use of women-specific CPCs in the early diagnosis of AMI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00470587.

PMID 24275751  JAMA Intern Med. 2014 Feb 1;174(2):241-9. doi: 10.1001/・・・
著者: Nadia A Khan, Stella S Daskalopoulou, Igor Karp, Mark J Eisenberg, Roxanne Pelletier, Meytal Avgil Tsadok, Kaberi Dasgupta, Colleen M Norris, Louise Pilote, GENESIS PRAXY Team
雑誌名: JAMA Intern Med. 2013 Nov 11;173(20):1863-71. doi: 10.1001/jamainternmed.2013.10149.
Abstract/Text IMPORTANCE: Little is known about whether sex differences in acute coronary syndrome (ACS) presentation exist in young patients and what factors determine absence of chest pain in ACS presentation.
OBJECTIVES: To evaluate sex differences in ACS presentation and to estimate associations between sex, sociodemographic, gender identity, psychosocial and clinical factors, markers of coronary disease severity, and absence of chest pain in young patients with ACS.
DESIGN, SETTING, PARTICIPANTS: We conducted a prospective cohort study of 1015 patients (30% women) 55 years or younger, hospitalized for ACS and enrolled in the GENESIS PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome) study (January 2009-September 2012).
MAIN OUTCOMES AND MEASURES: The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered during hospitalization.
RESULTS: The median age for both sexes was 49 years. Women were more likely to have non-ST-segment elevation myocardial infarction (37.5 vs 30.7; P = .03) and present without chest pain compared with men (19.0% vs 13.7%; P = .03). Patients without chest pain reported fewer symptoms overall and no discernable pattern of non-chest pain symptoms was found. In the multivariate model, being a woman (odds ratio [OR], 1.95 [95% CI, 1.23-3.11]; P = .005) and tachycardia (OR, 2.07 [95% CI, 1.20-3.56]; P = .009) were independently associated with ACS presentation without chest pain. Patients without chest pain did not differ significantly from those with chest pain in terms of ACS type, troponin level elevation, or coronary stenosis.
CONCLUSIONS AND RELEVANCE: Chest pain was the most common ACS symptom in both sexes. Although women were more likely to present without chest pain than men, absence of chest pain was not associated with markers of coronary disease severity. Strategies that explicitly incorporate assessment of common non-chest pain symptoms need to be evaluated.

PMID 24043208  JAMA Intern Med. 2013 Nov 11;173(20):1863-71. doi: 10.1・・・
著者: Steve Goodacre, Tom Locker, Francis Morris, Stephen Campbell
雑誌名: Acad Emerg Med. 2002 Mar;9(3):203-8.
Abstract/Text OBJECTIVES: To measure the predictive value and diagnostic performance of clinical features used to diagnose coronary syndromes in patients presenting with acute, undifferentiated chest pain.
METHODS: The clinical features of patients presenting to the authors' chest pain unit with acute, undifferentiated chest pain were prospectively recorded on a standard form. Admitted patients were followed up by case note review. Discharged patients were followed up as outpatients three days later. Six months after the emergency department visit, evidence of adverse events was searched for from the hospital computer database, case notes, and the patient's primary care physician. The authors tested the power of each feature to predict: 1) acute myocardial infarction (AMI) by World Health Organization criteria, and 2) any acute coronary syndrome (ACS), evidenced by cardiac testing, AMI, arrhythmia, death, or revascularization procedure within six months.
RESULTS: Eight hundred ninety-three patients were assessed, 34 (3.8%) with AMI and 81 (9.1%) with ACS. Features useful in the diagnosis of AMI were exertional pain [likelihood ratio (LR) = 2.35], pain radiating to the shoulder or both arms (LR = 4.07), and chest wall tenderness (LR = 0.3). Features useful in the diagnosis of ACS were exertional pain (LR = 2.06) and pain radiating to the shoulder, the left arm, or both arms (LR = 1.62). The site or nature of pain and the presence of nausea, vomiting, or diaphoresis were not predictive of AMI or ACS.
CONCLUSIONS: Important differences exist when clinical features are specifically investigated in patients with acute chest pain and a nondiagnostic electrocardiogram. Clinical features have a limited role to play in triage decision making.

PMID 11874776  Acad Emerg Med. 2002 Mar;9(3):203-8.
著者: J Mant, R J McManus, R A L Oakes, B C Delaney, P M Barton, J J Deeks, L Hammersley, R C Davies, M K Davies, F D R Hobbs
雑誌名: Health Technol Assess. 2004 Feb;8(2):iii, 1-158.
Abstract/Text OBJECTIVES: To ascertain the value of a range of methods - including clinical features, resting and exercise electrocardiography, and rapid access chest pain clinics (RACPCs) - used in the diagnosis and early management of acute coronary syndrome (ACS), suspected acute myocardial infarction (MI), and exertional angina.
DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Library and electronic abstracts of recent cardiological conferences.
REVIEW METHODS: Searches identified studies that considered patients with acute chest pain with data on the diagnostic value of clinical features or an electrocardiogram (ECG); patients with chronic chest pain with data on the diagnostic value of resting or exercise ECG or the effect of a RACPC. Likelihood ratios (LRs) were calculated for each study, and pooled LRs were generated with 95% confidence intervals. A Monte Carlo simulation was performed evaluating different assessment strategies for suspected ACS, and a discrete event simulation evaluated models for the assessment of suspected exertional angina.
RESULTS: For acute chest pain, no clinical features in isolation were useful in ruling in or excluding an ACS, although the most helpful clinical features were pleuritic pain (LR+ 0.19) and pain on palpation (LR+ 0.23). ST elevation was the most effective ECG feature for determining MI (with LR+ 13.1) and a completely normal ECG was reasonably useful at ruling this out (LR+ 0.14). Results from 'black box' studies of clinical interpretation of ECGs found very high specificity, but low sensitivity. In the simulation exercise of management strategies for suspected ACS, the point of care testing with troponins was cost-effective. Pre-hospital thrombolysis on the basis of ambulance telemetry was more effective but more costly than if performed in hospital. In cases of chronic chest pain, resting ECG features were not found to be very useful (presence of Q-waves had LR+ 2.56). For an exercise ECG, ST depression performed only moderately well (LR+ 2.79 for a 1 mm cutoff), although this did improve for a 2 mm cutoff (LR+ 3.85). Other methods of interpreting the exercise ECG did not result in dramatic improvements in these results. Weak evidence was found to suggest that RACPCs may be associated with reduced admission to hospital of patients with non-cardiac pain, better recognition of ACS, earlier specialist assessment of exertional angina and earlier diagnosis of non-cardiac chest pain. In a simulation exercise of models of care for investigation of suspected exertional angina, RACPCs were predicted to result in earlier diagnosis of both confirmed coronary heart disease (CHD) and non-cardiac chest pain than models of care based around open access exercise tests or routine cardiology outpatients, but they were more expensive. The benefits of RACPCs disappeared if waiting times for further investigation (e.g. angiography) were long (6 months).
CONCLUSIONS: Where an ACS is suspected, emergency referral is justified. ECG interpretation in acute chest pain can be highly specific for diagnosing MI. Point of care testing with troponins is cost-effective in the triaging of patients with suspected ACS. Resting ECG and exercise ECG are of only limited value in the diagnosis of CHD. The potential advantages of RACPCs are lost if there are long waiting times for further investigation. Recommendations for further research include the following: determining the most appropriate model of care to ensure accurate triaging of patients with suspected ACS; establishing the cost-effectiveness of pre-hospital thrombolysis in rural areas; determining the relative cost-effectiveness of rapid access chest pain clinics compared with other innovative models of care; investigating how rapid access chest pain clinics should be managed; and establishing the long-term outcome of patients discharged from RACPCs.

PMID 14754562  Health Technol Assess. 2004 Feb;8(2):iii, 1-158.
著者: Clifford J Swap, John T Nagurney
雑誌名: JAMA. 2005 Nov 23;294(20):2623-9. doi: 10.1001/jama.294.20.2623.
Abstract/Text CONTEXT: The chest pain history, physical examination, determination of coronary artery disease (CAD) risk factors, and the initial electrocardiogram compose the information immediately available to clinicians to help determine the probability of acute myocardial infarction (AMI) or acute coronary syndrome (ACS) in patients with chest pain. However, conflicting data exist about the usefulness of the chest pain history and which components are most useful.
OBJECTIVE: To identify the elements of the chest pain history that may be most helpful to the clinician in identifying ACS in patients presenting with chest pain.
EVIDENCE ACQUISITION: MEDLINE and Ovid were searched from 1970 to September 2005 by using specific key words and Medical Subject Heading terms. Reference lists of these articles and current cardiology textbooks were also consulted.
EVIDENCE SYNTHESIS: Certain chest pain characteristics decrease the likelihood of ACS or AMI, namely, pain that is stabbing, pleuritic, positional, or reproducible by palpation (likelihood ratios [LRs] 0.2-0.3). Conversely, chest pain that radiates to one shoulder or both shoulders or arms or is precipitated by exertion is associated with LRs (2.3-4.7) that increase the likelihood of ACS. The chest pain history itself has not proven to be a powerful enough predictive tool to obviate the need for at least some diagnostic testing. Combinations of elements of the chest pain history with other initially available information, such as a history of CAD, have identified certain groups that may be safe for discharge without further evaluation, but further study is needed before such a recommendation can be considered reasonable.
CONCLUSION: Although certain elements of the chest pain history are associated with increased or decreased likelihoods of a diagnosis of ACS or AMI, none of them alone or in combination identify a group of patients that can be safely discharged without further diagnostic testing.

PMID 16304077  JAMA. 2005 Nov 23;294(20):2623-9. doi: 10.1001/jama.294・・・
著者: Jin H Han, Christopher J Lindsell, Alan B Storrow, Samuel Luber, James W Hoekstra, Judd E Hollander, W Franklin Peacock, Charles V Pollack, W Brian Gibler, EMCREG i*trACS Investigators
雑誌名: Ann Emerg Med. 2007 Feb;49(2):145-52, 152.e1. doi: 10.1016/j.annemergmed.2006.09.027. Epub 2006 Dec 4.
Abstract/Text STUDY OBJECTIVE: We seek to determine whether cardiac risk factor burden (defined as the number of conventional cardiac risk factors present) is useful for the diagnosis of acute coronary syndromes in the emergency department (ED) setting.
METHODS: This was a post hoc analysis of the Internet Tracking Registry of Acute Coronary Syndromes (i*trACS) registry, which had 17,713 ED visits for suspected acute coronary syndromes. First visit for US patients who were not cocaine or amphetamine users, who did not leave against medical advice, and for whom ECG and demographic data were complete were included. Acute coronary syndrome was defined by 30-day revascularization, diagnostic-related group codes, or death within 30 days, with positive cardiac biomarkers at index hospitalization. Cardiac risk factors were diabetes, hypertension, smoking, hypercholesterolemia, and family history of coronary artery disease. Cardiac risk factor burden was defined as the number of risk factors present. Because multiple logistic regression analysis revealed that age modified the relationship between cardiac risk factor burden and acute coronary syndromes, a stratified analysis was performed for 3 age categories: younger than 40, 40 to 65, and older than 65 years. Positive likelihood ratios and negative likelihood ratios with their 95% confidence intervals (CIs) were calculated for each total risk factor cutoff.
RESULTS: Of 10,806 eligible patients, 871 (8.1%) had acute coronary syndromes. In patients younger than 40 years, having no risk factors had a negative likelihood ratio of 0.17 (95% CI 0.04 to 0.66), and having 4 or more risk factors had a positive likelihood ratio of 7.39 (95% CI 3.09 to 17.67). In patients between 40 and 65 years of age, having no risk factors had a negative likelihood ratio of 0.53 (95% CI 0.40 to 0.71), and having 4 or more risk factors had a positive likelihood ratio of 2.13 (95% CI 1.66 to 2.73). In patients older than 65 years, having no risk factors had a negative likelihood ratio of 0.96 (95% CI 0.74 to 1.23), and having 4 or more risk factors had a positive likelihood ratio of 1.09 (95% CI 0.64 to 1.62).
CONCLUSION: Cardiac risk factor burden has limited clinical value in diagnosing acute coronary syndromes in the ED setting, especially in patients older than 40 years.

PMID 17145112  Ann Emerg Med. 2007 Feb;49(2):145-52, 152.e1. doi: 10.1・・・
著者: José A Barrabés, Jaume Figueras, Cristina Moure, Josefa Cortadellas, Jordi Soler-Soler
雑誌名: Circulation. 2003 Aug 19;108(7):814-9. doi: 10.1161/01.CIR.0000084553.92734.83. Epub 2003 Jul 28.
Abstract/Text BACKGROUND: ST-segment elevation in lead aVR has been associated with severe coronary artery lesions in patients with acute coronary syndromes, but the prognostic significance of this finding is unknown.
METHODS AND RESULTS: We analyzed the initial ECG in 775 consecutive patients admitted to our center with a first acute myocardial infarction without ST-segment elevation in leads other than aVR or V1. The rates of in-hospital death in patients without (n=525) and with 0.05 to 0.1 mV (n=116) or > or =0.1 mV (n=134) of ST-segment elevation in lead aVR were 1.3%, 8.6%, and 19.4%, respectively (P<0.001). After adjustment for the baseline clinical predictors and for ST-segment depression on admission, the odds ratios for death in the last 2 groups were, respectively, 4.2 (95% CI, 1.5 to 12.2) and 6.6 (95% CI, 2.5 to 17.6). The rates of recurrent ischemic events and heart failure during hospital stay also increased in a stepwise fashion among the groups, whereas creatine kinase-MB levels were similar. Among the 437 patients that were catheterized within 6 months, the prevalence of left main or 3-vessel coronary artery disease in the 3 groups was 22.0%, 42.6%, and 66.3%, respectively (P<0.001).
CONCLUSIONS: Lead aVR contains important short-term prognostic information in patients with a first non-ST-segment elevation acute myocardial infarction. Because the poorer outcome predicted by ST-segment elevation in lead aVR seems to be related to a more severe coronary artery disease, an early invasive approach might be especially beneficial in patients presenting with this finding.

PMID 12885742  Circulation. 2003 Aug 19;108(7):814-9. doi: 10.1161/01.・・・
著者: Seth W Glickman, Frances S Shofer, Michael C Wu, Matthew J Scholer, Adanma Ndubuizu, Eric D Peterson, Christopher B Granger, Charles B Cairns, Lawrence T Glickman
雑誌名: Am Heart J. 2012 Mar;163(3):372-82. doi: 10.1016/j.ahj.2011.10.021.
Abstract/Text BACKGROUND: Current guidelines recommend an immediate (eg, <10 minutes) 12-lead electrocardiogram (ECG) to identify ST-elevation myocardial infarction (STEMI) among patients presenting to the emergency department (ED) with chest pain. Yet, one third of all patients with myocardial infarction do not have chest pain. Our objective was to develop a practical approach to identify patients, especially those without chest pain, who require an immediate ECG in the ED to identify STEMI.
METHODS: An ECG prioritization rule was derived and validated using classification and regression tree analysis among >3 million ED visits to 107 EDs from 2007 to 2008.
RESULTS: The final study population included 3,575,178 ED patient visits; of these, 6,464 (0.18%) were diagnosed with STEMI. Overall, 1,413 (21.9%) of patients with STEMI did not present to the ED with chest pain. Major predictors of those requiring an immediate ECG in the ED included age ≥30 years with chest pain; age ≥50 years with shortness of breath, altered mental status, upper extremity pain, syncope, or generalized weakness; and those with age ≥80 years with abdominal pain or nausea/vomiting. When the ECG prioritization rule was applied to a validation sample, it had a sensitivity of 91.9% (95% CI 90.9%-92.8%) for STEMI and a negative predictive value 99.98% (95% CI 99.98%-99.98%).
CONCLUSION: A simple ECG prioritization rule based on age and presenting symptoms in the ED can identify patients during triage who are at high risk for STEMI and therefore should receive an immediate 12-lead ECG, often before they are seen by a physician.

Copyright © 2012 Mosby, Inc. All rights reserved.
PMID 22424007  Am Heart J. 2012 Mar;163(3):372-82. doi: 10.1016/j.ahj.・・・
著者: M Kosuge, K Kimura, T Ishikawa, T Shimizu, K Hibi, N Nozawa, S Umemura
雑誌名: Heart. 2005 Jan;91(1):95-6. doi: 10.1136/hrt.2003.030973.
Abstract/Text
PMID 15604347  Heart. 2005 Jan;91(1):95-6. doi: 10.1136/hrt.2003.03097・・・
著者: C P Cannon, C H McCabe, P H Stone, W J Rogers, M Schactman, B W Thompson, D J Pearce, D J Diver, C Kells, T Feldman, M Williams, R S Gibson, M W Kronenberg, L I Ganz, H V Anderson, E Braunwald
雑誌名: J Am Coll Cardiol. 1997 Jul;30(1):133-40.
Abstract/Text OBJECTIVES: We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non-Q wave myocardial infarction (MI).
BACKGROUND: Although the ECG is the most widely used test for evaluating patients with unstable angina and non-Q wave MI, little prospective information is available on its value in predicting outcome in the current era of aggressive medical and interventional therapy.
METHODS: ECGs with the qualifying episode of pain were analyzed in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, a prospective study of patients admitted to the hospital with unstable angina or non-Q wave MI.
RESULTS: New ST segment deviation > or = 1 mm was present in 14.3% of 1,416 enrolled patients, isolated T wave inversion in 21.9% and left bundle branch block (LBBB) in 9.0%. By 1-year follow-up, death or MI occurred in 11% of patients with > or = 1 mm ST segment deviation compared with 6.8% of patients with new, isolated T wave inversion and 8.2% of those with no ECG changes (p < 0.001 when comparing ST with no ST segment deviation). Two other high risk groups were identified: those with only 0.5-mm ST segment deviation and those with LBBB, whose rates of death or MI by 1 year were 16.3% and 22.9%, respectively. On multivariate analysis, ST segment deviation of either > or = 1 mm or > or = 0.5 mm remained independent predictors of death or MI by 1 year.
CONCLUSIONS: The admission ECG is very useful in risk stratifying patients with non-Q wave MI. The new criteria of not only > or = 1-mm ST segment deviation but also > or = 0.5-mm ST segment deviation or LBBB identify high risk patients, whereas T wave inversion does not add to the clinical history in predicting outcome.

PMID 9207634  J Am Coll Cardiol. 1997 Jul;30(1):133-40.
著者: Cynthia M Westerhout, Yuling Fu, Michael S Lauer, Stefan James, Paul W Armstrong, Eyad Al-Hattab, Robert M Califf, Maarten L Simoons, Lars Wallentin, Eric Boersma, GUSTO-IV ACS Trial Investigators
雑誌名: J Am Coll Cardiol. 2006 Sep 5;48(5):939-47. doi: 10.1016/j.jacc.2006.04.085.
Abstract/Text OBJECTIVES: The purpose of this study was to develop 30-day and 1-year risk stratification models for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients that incorporate quantitative ST-segment depression and novel biomarkers.
BACKGROUND: Several novel biomarkers have changed the risk profile of ACS; thus, the reassessment of traditional indicators such as ST-segment depression in this new context is warranted.
METHODS: Multivariable logistic regression was used to identify significant predictors of 30-day death and death/myocardial infarction (MI) and 1-year mortality in 7,800 NSTE-ACS patients enrolled in the GUSTO-IV (Global Utilization of Strategies to Open Occluded Arteries-IV ACS) trial between 1998 and 2000.
RESULTS: Among all other predictors, the degree of ST-segment depression had the highest prognostic value for 30-day death, 30-day death/MI, and 1-year death. Troponin T (TnT), creatinine clearance, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart rate, and age were also highly influential on adverse outcomes. Unlike TnT and NT-proBNP, C-reactive protein was only predictive of long-term death. In contrast to mortality, the contribution of TnT to predicting 30-day death/MI increased, whereas NT-proBNP's role was attenuated. The discriminatory power was excellent (c-index [adjusted for over-optimism]: 0.82 [30-day death]; 0.72 [30-day death/MI]; 0.81 [1-year]).
CONCLUSIONS: In this large contemporary study of NSTE-ACS patients, novel insights into risk stratification were observed-in particular, the utility of quantitative ST-segment depression and multiple biomarkers. Collection of these indicators in future NSTE-ACS populations is recommended to evaluate generalizability and clinical application of these findings.

PMID 16949483  J Am Coll Cardiol. 2006 Sep 5;48(5):939-47. doi: 10.101・・・
著者: Stefano Savonitto, Mauricio G Cohen, Alessandro Politi, Michael P Hudson, David F Kong, Yao Huang, Karen S Pieper, Francesco Mauri, Galen S Wagner, Robert M Califf, Eric J Topol, Christopher B Granger
雑誌名: Eur Heart J. 2005 Oct;26(20):2106-13. doi: 10.1093/eurheartj/ehi395. Epub 2005 Jun 29.
Abstract/Text AIMS: We sought to determine whether the extent of myocardial ischaemia on the admission electrocardiogram (ECG) has independent predictive value for short-term risk stratification of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). Although the presence of ischaemic ECG changes on admission has been shown to predict outcome, the relationship between the extent of ECG changes and the risk of cardiac events is still ill defined.
METHODS AND RESULTS: We analysed the admission ECGs of 5192 ACS patients enrolled in the GUSTO-IIb trial, without an ECG indication for thrombolysis. ECG tracings showing one or more of the following were eligible: ST-segment depression >0.5 mm, T-wave inversion >1 mm, and ST-segment elevation >0.5 mm but <1 mm. ECG variables associated with unfavourable 30 day outcomes in a univariable analysis were further assessed in a multivariable logistic regression model including independent clinical predictors. In the multivariable clinical, enzymatic, and ECG model, the sum of ST-segment depression (in millimetres) in all leads was a powerful independent predictor of 30 day death (P<0.0001), with a continuous increase in risk with the extent of ST-segment depression. The sum of ST-segment depression (P<0.0001) and the presence of minimal inferior ST-segment elevation (P<0.0001) or anterior ST-segment elevation (P=0.0182) were also independent predictors of the composite of death and myocardial infarction or reinfarction. The extent of ST-segment depression showed a highly significant correlation with the prevalence of three-vessel (P<0.0001) or left main coronary disease (P<0.0001), and also with the peak levels of creatine kinase (P<0.0001) during the index episode of ACS.
CONCLUSION: In patients with NSTE ACS, the sum of ST-segment depression in all ECG leads is a powerful predictor of all-cause mortality at 30 days, independent of clinical variables and correlates with the extent and severity of coronary artery disease. The presence of even minimal (<1 mm) ST-segment elevation in anterior or inferior leads is independently associated with adverse outcomes.

PMID 15987706  Eur Heart J. 2005 Oct;26(20):2106-13. doi: 10.1093/eurh・・・
著者: Lene Holmvang, Peter Clemmensen, Bertil Lindahl, Bo Lagerqvist, Per Venge, Galen Wagner, Lars Wallentin, Peer Grande
雑誌名: J Am Coll Cardiol. 2003 Mar 19;41(6):905-15.
Abstract/Text OBJECTIVES: The aim of the present study was to evaluate whether the effect of an early invasive treatment strategy differed between patients sub-grouped according to their severity of myocardial ischemia, as evaluated by quantitative electrocardiographic (ECG) analysis at the time of presentation. The present study is a sub-study of the previously published Fast Revascularization during InStability in Coronary artery disease trial (FRISC-II).
BACKGROUND: An early invasive treatment strategy has been shown to be the preferable treatment for non-ST-segment elevation acute coronary syndromes (ACS). The population of patients with unstable coronary artery disease is heterogeneous regarding both the underlying pathology and prognosis. Early risk stratification is important to select patient subgroups that will benefit the most from a given treatment.
METHODS: In 2,201 patients with non-ST-segment elevation ACS, the ischemic burden at hospital admission was determined by quantitative measurements of ST-T-segment deviations on the ECG. The patients were subsequently sub-grouped in tertiles based on the amount of ST-segment deviation. The primary end point for this analysis was death or myocardial infarction (MI) within one year after study inclusion.
RESULTS: The invasive treatment strategy produced a reduction of approximately 50% in death or MI among the patients with intermediate or major ST-segment deviation. The findings were independent of age, gender, or troponin T status. The patients with confounding factors precluding ST analysis had a poor outcome regardless of the treatment strategy.
CONCLUSIONS: Ischemic burden on the admission ECG identifies patients with ACS who benefit the most from an invasive treatment strategy. When the standard ECG is scrutinized with complete quantitative measurements, it provides independent information on prognosis and benefit of treatment.

PMID 12651033  J Am Coll Cardiol. 2003 Mar 19;41(6):905-15.
著者: Padma Kaul, L Kristin Newby, Yuling Fu, Vic Hasselblad, Kenneth W Mahaffey, Robert H Christenson, Robert A Harrington, E Magnus Ohman, Eric J Topol, Robert M Califf, Frans Van de Werf, Paul W Armstrong, PARAGON-B Investigators
雑誌名: J Am Coll Cardiol. 2003 Feb 5;41(3):371-80.
Abstract/Text OBJECTIVES: Our primary objective was to examine the prognostic relationship between baseline quantitative ST-segment depression (ST) and cardiac troponin T (cTnT) elevation. The secondary objectives were to: 1) examine whether ST provided additional insight into therapeutic efficacy of glycoprotein IIb/IIIa therapy similar to that demonstrated by cTnT; and 2) explore whether the time to evaluation impacted on each marker's relative prognostic utility.
BACKGROUND: The relationship between the baseline electrocardiogram (ECG) and cTnT measurements in risk-stratifying patients presenting with acute coronary syndromes (ACS) has not been evaluated comprehensively.
METHODS: The study population consisted of 959 patients enrolled in the cTnT substudy of the Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON)-B trial. Patients were classified as having no ST (n = 387), 1 mm ST (n = 433), and ST > or =2 mm (n = 139). Forty-percent (n = 381) were classified as cTnT-positive based on a definition of > or =0.1 ng/ml.
RESULTS: Six-month death/(re)myocardial infarction rates were 8.4% among cTnT-negative patients with no ST and 26.8% among cTnT-positive patients with ST > or =2 mm. On ECGs done after 6 h of symptom onset, ST > or =2 mm was associated with higher risk compared to its presence on ECGs done earlier (odds ratio [OR] 7.3 vs. 2.1). In contrast, the presence of elevated cTnT within 6 h of symptom was associated with a higher risk of adverse events compared with elevations after 6 h (OR 2.4 vs. 1.5).
CONCLUSIONS: Quantitative ST and cTnT status are complementary in assessing risk among ACS patients and both should be employed to determine prognosis and assist in medical decision making.

PMID 12575962  J Am Coll Cardiol. 2003 Feb 5;41(3):371-80.
著者: Peter Damman, Lene Holmvang, Jan G P Tijssen, Bo Lagerqvist, Tim C Clayton, Stuart J Pocock, Fons Windhausen, Alexander Hirsch, Keith A A Fox, Lars Wallentin, Robbert J de Winter
雑誌名: Am J Cardiol. 2012 Jan 1;109(1):6-12. doi: 10.1016/j.amjcard.2011.08.002. Epub 2011 Sep 23.
Abstract/Text The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non-ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data.

Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 21944677  Am J Cardiol. 2012 Jan 1;109(1):6-12. doi: 10.1016/j.am・・・
著者: Sally J Aldous, Mark Richards, Louise Cullen, Richard Troughton, Martin Than
雑誌名: CMAJ. 2012 Mar 20;184(5):E260-8. doi: 10.1503/cmaj.110773. Epub 2012 Jan 30.
Abstract/Text BACKGROUND: High-sensitivity troponin assays are now available for clinical use. We investigated whether early measurement with such an assay is superior to a conventional assay in the evaluation of acute coronary syndromes.
METHODS: Patients presenting to an emergency department with chest pain who did not have ST-segment elevation were prospectively recruited from November 2007 to December 2010. Patients underwent serial testing with a conventional cardiac troponin I assay. Samples were also obtained at presentation and two hours later for measurement of troponin T levels using a high-sensitivity assay. The primary outcome was diagnosis of myocardial infarction on admission; secondary outcomes were death, myocardial infarction and heart failure at one year.
RESULTS: Of the 939 patients enrolled in the study, 205 (21.8%) had myocardial infarction. By two hours after presentation, the high-sensitivity troponin T assay at the cut-off point of the 99th percentile of the general population (14 ng/L) had a sensitivity of 92.2% (95% confidence interval [CI] 88.1%-95.0%) and a specificity of 79.7% (95% CI 78.6%-80.5%) for the diagnosis of non-ST-segment myocardial infarction. The sensitivity of the assay at presentation was 100% among patients who presented four to six hours after symptom onset. By one year, the high-sensitivity troponin T assay was found to be superior than the conventional assay in predicting death (hazard ratio [HR] 5.4, 95% CI 2.7-10.7) and heart failure (HR 27.8, 95% CI 6.6-116.4), whereas the conventional assay was superior in predicting nonfatal myocardial infarction (HR 4.0, 95% CI 2.4-6.7).
INTERPRETATION: The high-sensitivity troponin T assay at the cut-off point of the 99th percentile was highly sensitive for the diagnosis of myocardial infarction by two hours after presentation and had prognostic utility beyond that of the conventional assay. To rule out myocardial infarction, the optimal time to test a second sample using the high-sensitivity troponin T level may be four to six hours after symptom onset, but this finding needs verification in future studies before it can become routine practice.

PMID 22291171  CMAJ. 2012 Mar 20;184(5):E260-8. doi: 10.1503/cmaj.1107・・・
著者: Martin Than, Sally Aldous, Sarah Jane Lord, Stephen Goodacre, Christopher M A Frampton, Richard Troughton, Peter George, Christopher Michael Florkowski, Michael Ardagh, David Smyth, David Lewis Jardine, William Frank Peacock, Joanna Young, Gregory Hamilton, Joanne M Deely, Louise Cullen, A Mark Richards
雑誌名: JAMA Intern Med. 2014 Jan;174(1):51-8. doi: 10.1001/jamainternmed.2013.11362.
Abstract/Text IMPORTANCE: Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge.
OBJECTIVE: To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting.
DESIGN, SETTING, AND PARTICIPANTS: A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up.
INTERVENTIONS: An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control.
MAIN OUTCOMES AND MEASURES: Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days.
RESULTS: Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation.
CONCLUSIONS AND RELEVANCE: Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required.
TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12610000766011.

PMID 24100783  JAMA Intern Med. 2014 Jan;174(1):51-8. doi: 10.1001/jam・・・
著者: T K Bakshi, M K F Choo, C C Edwards, A G Scott, H H Hart, G P Armstrong
雑誌名: Intern Med J. 2002 Nov;32(11):520-5.
Abstract/Text BACKGROUND: The new definition of myocardial infarction (MI) emphasizes the pre-eminent role of troponin for diagnosis. Troponin rise indicates myocardial injury, but is not synonymous with infarction or ischaemia.
AIMS: To review the precipitating event for troponin elevation in patients with angiographically normal coronary arteries, in a district general hospital.
METHODS: Consecutive patients with elevated troponin I (TnI) who underwent angiography for suspected coronary disease were included in the present study if they had normal or mild disease (<50% diameter loss without complex features or thrombus). Precipitating event for TnI elevation was assigned on the totality of clinical evidence.
RESULTS: Twenty-one patients qualified, with an average age of 50 years (range 33-73). Sixty-two per cent of participants were female. Troponin release was attributed to tachycardia in six patients, only two of whom had haemodynamic compromise. Physical exertion was the precipitating factor in two patients; pericarditis in two patients; and severe congestive heart failure in one patient. Ten of 21 patients had no identifiable cause for a rise in TnI concentration. Five of 21 patients had left-ventricular wall motion abnormalities. There were no deaths or MI at 41 +/- 24 weeks follow up.
CONCLUSION: Troponin is a sensitive marker of myocardial injury and may rise following apparently minor insults. A rise in TnI concentration may have a cause other than acute coronary syndrome and may occur without significant angiographic coronary artery disease.

PMID 12412934  Intern Med J. 2002 Nov;32(11):520-5.
著者: S G Sawada, D S Segar, T Ryan, S E Brown, A M Dohan, R Williams, N S Fineberg, W F Armstrong, H Feigenbaum
雑誌名: Circulation. 1991 May;83(5):1605-14.
Abstract/Text BACKGROUND: Two-dimensional echocardiography performed during dobutamine infusion has been proposed as a potentially useful method for detecting coronary artery disease. However, the safety and diagnostic value of dobutamine stress echocardiography has not been established.
METHODS AND RESULTS: In this study, echocardiograms were recorded during step-wise infusion of dobutamine to a maximum dose of 30 micrograms/kg/min in 103 patients who also underwent quantitative coronary angiography. The echocardiograms were digitally stored and displayed in a format that allowed simultaneous analysis of rest and stress images. Development of a new abnormality in regional function was used as an early end point for the dobutamine infusion. No patient had a symptomatic arrhythmia or complications from stress-induced ischemia. Significant coronary artery disease (greater than or equal to 50% diameter stenosis) was present in 35 of 55 patients who had normal echocardiograms at rest. The sensitivity and specificity of dobutamine-induced wall motion abnormalities for coronary artery disease was 89% (31 of 35) and 85% (17 of 20), respectively. The sensitivity was 81% (17 of 21) in those with one-vessel disease and 100% (14 of 14) in those with multivessel or left main disease. Forty-one of 48 patients with abnormal echocardiograms at baseline had localized rest wall motion abnormalities. Fifteen had coronary artery disease confined to regions that had abnormal rest wall motion, and 26 had disease remote from these regions. Thirteen of 15 patients (87%) without remote disease did not develop remote stress-induced abnormalities, and 21 of 26 (81%) who had remote disease developed corresponding abnormalities.
CONCLUSIONS: Echocardiography combined with dobutamine infusion is a safe and accurate method for detecting coronary artery disease and for predicting the extent of disease in those who have localized rest wall motion abnormalities.

PMID 1673646  Circulation. 1991 May;83(5):1605-14.
著者: Melvin D Cheitlin, William F Armstrong, Gerard P Aurigemma, George A Beller, Fredrick Z Bierman, Jack L Davis, Pamela S Douglas, David P Faxon, Linda D Gillam, Thomas R Kimball, William G Kussmaul, Alan S Pearlman, John T Philbrick, Harry Rakowski, Daniel M Thys, Elliott M Antman, Sidney C Smith, Joseph S Alpert, Gabriel Gregoratos, Jeffrey L Anderson, Loren F Hiratzka, Sharon Ann Hunt, Valentin Fuster, Alice K Jacobs, Raymond J Gibbons, Richard O Russell, American College of Cardiology, American Heart Association, American Society of Echocardiography
雑誌名: Circulation. 2003 Sep 2;108(9):1146-62. doi: 10.1161/01.CIR.0000073597.57414.A9.
Abstract/Text
PMID 12952829  Circulation. 2003 Sep 2;108(9):1146-62. doi: 10.1161/01・・・
著者: R S Horowitz, J Morganroth, C Parrotto, C C Chen, J Soffer, F J Pauletto
雑誌名: Circulation. 1982 Feb;65(2):323-9.
Abstract/Text To define the role of portable two-dimensional echocardiography (2-D echo) in the immediate diagnosis of acute chest pain syndrome, 80 consecutive patients were studied. Adequate 2-D echo studies were obtained in 65 (81%). Thirty-three patients had clinical evidence of transmural or nontransmural acute myocardial infarction (AMI), 18 of whom had nondiagnostic initial ECGs. Thirty-two did not have a clinical AMI. Thirty-one of the 33 (94%) patients with clinical AMI had regional wall motion abnormalities on the initial 2-D echo; the other two had uncomplicated nontransmural AMIs, diagnosed only by ECG in one and by ECG and moderate elevation of CK-MB isoenzyme in the other. Twenty-seven of the 32 patients without clinical AMI had normal regional wall motion on the initial 2-D echo and none had a complication (severe arrhythmia, recurrent pain, heart failure or death) during the hospital course. Conversely, 10 of the 36 patients with initial 2-D echo regional wall motion abnormalities had a complication (p less than 0.05). Thus, in patients with acute chest pain syndrome, an initial 2-D echo that shows no regional wall motion abnormality suggests that such patients will not develop an AMI or clinical complication during the hospital course. An initial 2-D echo with regional wall motion abnormality identifies a high-risk group of patients who are likely to have AMI and important cardiac complications and may, therefore, benefit from admission to an intensive care unit.

PMID 7053890  Circulation. 1982 Feb;65(2):323-9.
著者: J H Stein, A Neumann, L M Preston, B J Vandenberg, J E Parrillo, J E Calvin, R H Marcus
雑誌名: Clin Cardiol. 1998 Oct;21(10):725-30.
Abstract/Text BACKGROUND: Current protocols for risk stratification of patients with acute chest pain syndromes rely on clinical parameters and are oriented toward identification of patients at high risk for adverse cardiac events; however, this paradigm for risk stratification does not adequately address the observation that adverse cardiac events are relatively uncommon in this population. In an era of cost containment, consideration also should be given to identification of patients at low risk for adverse cardiac events, who may be safely discharged without expensive inpatient hospitalization.
HYPOTHESIS: The purpose of this study was to develop echocardiographic predictors that identify unstable angina patients at low risk for adverse cardiac events and that discriminate between low- and high-risk patients.
METHODS: The predictive accuracy of retrospectively determined echocardiographic predictors were compared in a population-based sample of 66 consecutive unstable angina patients undergoing echocardiography within 24 h of admission.
RESULTS: Echocardiographic predictors of adverse events included wall motion score index > or = 0.2, ejection fraction < or = 40%, and mitral regurgitation severity > 2. One or more echocardiographic predictors of adverse events were present in 32 patients (48%). A composite echocardiographic predictor of adverse events was specific, had a high positive predictive value for the identification of high-risk patients, and discriminated between unstable angina patients at high and low risk for adverse cardiac events.
CONCLUSION: Echocardiographic predictors of adverse events are specific and discriminate between unstable angina patients at high and low risk for adverse cardiac events.

PMID 9789692  Clin Cardiol. 1998 Oct;21(10):725-30.
著者: P J Colon, J S Guarisco, J Murgo, J Cheirif
雑誌名: Am J Cardiol. 1998 Nov 15;82(10):1282-4, A10.
Abstract/Text We followed 108 patients presenting to the emergency department with atypical chest pain and triaged with stress echocardiography. One-year cardiac event-free survival was 100% with a negative stress echocardiogram and 25% with a positive study.

PMID 9832109  Am J Cardiol. 1998 Nov 15;82(10):1282-4, A10.
著者: W B Gibler, J P Runyon, R C Levy, M R Sayre, R Kacich, C R Hattemer, C Hamilton, J W Gerlach, R A Walsh
雑誌名: Ann Emerg Med. 1995 Jan;25(1):1-8.
Abstract/Text STUDY OBJECTIVE: To evaluate a comprehensive diagnostic 9-hour evaluation (Heart ER Program) for patients with possible acute ischemic coronary syndromes.
DESIGN: Retrospective review of consecutive patients.
SETTING: Urban tertiary care emergency department.
PARTICIPANTS: A total of 1,010 patients with symptoms suggestive of acute ischemic coronary syndrome was enrolled in the Heart ER Program over the first 32 months of operation. Patients with history of coronary artery disease, hemodynamic instability, acute ST-segment elevation or depression of more than 1 mm, or a clinical syndrome consistent with unstable angina were directly admitted to the hospital.
INTERVENTION: Patients underwent serial testing for creatine kinase (CK-MB) on presentation to the Heart ER and 3, 6, and 9 hours later with continuous 12-lead ECGs/serial ST-segment trend monitoring for 9 hours. Two-dimensional echocardiography and graded exercise testing were performed in the ED after the 9-hour evaluation period.
RESULTS: Of 1,010 patients, 829 (82.1%) were released home from the ED; 153 (15.1%) required admission for further cardiac evaluation. Fifty-two of 153 (33.9%) admitted patients were found to have a cardiac cause for their symptoms; 43 had acute ischemic coronary syndromes (12, acute myocardial infarction; 31, angina or unstable angina).
CONCLUSION: The Heart ER program provides an effective method for evaluating low- to moderate-risk patients with possible acute ischemic coronary syndrome in the ED setting.

PMID 7802357  Ann Emerg Med. 1995 Jan;25(1):1-8.
著者: M Buchsbaum, E Marshall, B Levine, M Bennett, A DiSabatino, R O'Connor, N Jasani
雑誌名: Acad Emerg Med. 2001 Feb;8(2):196-9.
Abstract/Text OBJECTIVE: Patients with a low risk of coronary artery disease (CAD) presenting to the emergency department (ED) with chest pain pose a diagnostic dilemma because a small percentage will suffer an acute myocardial infarction (MI) and sudden death. The authors conducted this study to determine whether exercise stress echocardiography (ESE) could be used to further support the safe discharge of these low-risk patients.
METHODS: A convenience sample of patients > or =30 years of age without a prior cardiac history who presented to an academic community hospital with chest pain, normal initial creatine kinase, and electrocardiography without ischemic changes underwent ESE within 6 +/- 1.7 hours (mean +/- SD). Abnormal ESE was defined as regional wall motion abnormality at rest or after exercise. The ED disposition and three- and six-month follow-up for cardiac events were recorded. This was a prospective observational cohort study.
RESULTS: Of a total of 149 eligible patients, 145 completed the study. The mean age (+/-SD) was 47 +/- 9 years; 56% were male. No adverse events were noted during ESE. Seven patients (5%) had abnormal ESE (2 with rest wall motion abnormalities and 5 with exercise-induced wall motion abnormalities). Five of the seven underwent cardiac catheterization; three had CAD. All patients received telephone follow-up at three months and six months. Of the 138 patients with a normal ESE, all were free of cardiac events at three months. One patient had a non-Q-wave MI at six months (negative predictive value = 99.3%, 95% CI = 97.8% to 100%).
CONCLUSIONS: Exercise stress echocardiography can be used to evaluate low-risk chest pain patients in the ED. Patients with a normal ESE may be considered for discharge with minimal risk of sequelae.

PMID 11157301  Acad Emerg Med. 2001 Feb;8(2):196-9.
著者: Alberto Conti, Barbara Paladini, Simone Toccafondi, Simone Magazzini, Iacopo Olivotto, Ferdinando Galassi, Cesco Pieroni, Gennaro Santoro, David Antoniucci, Giancarlo Berni
雑誌名: Am Heart J. 2002 Oct;144(4):630-5.
Abstract/Text BACKGROUND: In patients seen at the emergency department (ED) with chest pain (CP), noninvasive diagnostic strategies may differentiate patients at high or intermediate risk from those at low-risk for cardiovascular events and optimize the use of high-cost resources. However, in welfare healthcare systems, the feasibility, accuracy, and potential benefits of such management strategy need further investigation.
METHODS: A total of 13,762 consecutive patients with CP were screened, and their conditions were defined as high, intermediate, and low risk for short-term cardiovascular events. Patients at high and intermediate risk were admitted. Patients at low risk were discharged from the ED if first line (<6 hours, including electrocardiogram, troponins, and serum cardiac markers) or second line short-term evaluation (<24 hours, including echocardiogram, rest or stress 99m-Tc myocardial scintigraphy, exercise tolerance test, or stress-echocardiography) had negative results. Patients with a diagnosis of coronary artery disease (CAD) were admitted. Patients without evidence of cardiovascular disease underwent screening for psychiatric and gastroesophageal disorders. Inhospital mortality rate was assessed in all patients.
RESULTS: Among patients at high and intermediate risk (n = 9335), 2420 patients had acute myocardial infarction (26%, 10.6% mortality rate), 3764 had unstable angina (40%, 1.1% mortality rate), 129 had aortic dissection (1.4%, 23.3% mortality rate), and 408 had pulmonary embolism (4%, 27.6% mortality rate). The remaining 2614 had chronic coronary heart disease in the context of multiple pathology (n = 2256) or pleural or pericardial diseases (n = 358). Among patients at low risk (n = 4427), 2672 were discharged at <6 hours (60%, 0.2% incidence rate of nonfatal CAD at 6 months) and 870 patients were discharged at <24 hours (20%, no CAD at follow-up). The remaining 885 patients were recognized as having CAD (20%, 1.1% inhospital mortality rate). Finally, half of the patients without CAD had active gastroesophageal or anxiety disorders.
CONCLUSION: An effective screening program with an observation area inside the ED (1) could be implemented in a public healthcare environment and contribute significantly to the reduction of admissions, (2) could optimize the management of patients at high and intermediate risk and succeed in recognizing CAD in 20% of patients at low risk, and (3) could allow screening for alternative causes of CP in patients without evidence of CAD.

PMID 12360158  Am Heart J. 2002 Oct;144(4):630-5.
著者: Alberto Conti, Lucia Sammicheli, Chiara Gallini, Egidio Natalino Costanzo, David Antoniucci, Giuseppe Barletta
雑誌名: Am Heart J. 2005 May;149(5):894-901. doi: 10.1016/j.ahj.2004.09.048.
Abstract/Text OBJECTIVES: The aim of the study was to compare head-to-head the performance of exercise tolerance test-stress echocardiography (ex-Echo) and exercise stress-perfusion nuclear imaging (exercise-single-photon emission computed tomography [ex-SPECT]) for the diagnosis of coronary artery disease (CAD) in patients evaluated at the chest pain unit with delay from chest pain (CP) onset.
BACKGROUND: As an early triage strategy for CAD in emergency medicine, ex-Echo could have the advantage of widespread availability and low costs.
METHODS: In the years 2000-2002, 503 consecutive patients (mean age 60 years) with recent (<24 hours) CP and nonischemic electrocardiogram (ECG), in whom CAD remained undiagnosed after first line 6-hour work-up including serum markers of myocardial injury and resting echocardiogram, underwent ex-Echo and ex-SPECT within 24 hours. Patients with (+)ex-Echo or (+)ex-SPECT or (+)ex-ECG or abnormal troponin I were referred to coronary angiography; otherwise, they were discharged and followed up. End points were coronary stenosis > or =50% and cardiovascular events at 6-month follow-up.
RESULTS: Ninety-nine patients (20%) had (+)ex-Echo and 121 (24%) (+)ex-SPECT; CAD was diagnosed in 81% and 67%, respectively; positive tests were concordant in 69%. In negative ex-Echo and ex-SPECT, final evidence of CAD emerged in 14 and 13, respectively. Ex-Echo demonstrated higher accuracy than ex-SPECT (93% +/- 1% vs 89% +/- 1%), optimal specificity (95% +/- 5% vs 90% +/- 5%), and positive predictive value (81% +/- 4% vs 67% +/- 4%); moreover, in the case of (-)ex-ECG, observed effective likelihood ratio indicates a (+)synergy between ex-ECG and ex-Echo.
CONCLUSIONS: Ex-Echo can be an effective diagnostic strategy in the early triage of CP patients, improving diagnosis in case of (-)ex-ECG and reducing unnecessary angiography number. Its drawback is represented by the 5% of missed diagnosis.

PMID 15894974  Am Heart J. 2005 May;149(5):894-901. doi: 10.1016/j.ahj・・・
著者: Radha Bholasingh, Jan Hein Cornel, Otto Kamp, Jan P van Straalen, Gerard T Sanders, Jan G P Tijssen, Victor A W M Umans, Cees A Visser, Robbert J de Winter
雑誌名: J Am Coll Cardiol. 2003 Feb 19;41(4):596-602.
Abstract/Text OBJECTIVES: We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography (DSE) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram (ECG) and a negative serial troponin T.
BACKGROUND: Noninvasive stress testing is recommended before discharge or within 72 h in patients with low-risk chest pain. The prognostic value of immediate DSE has not been studied in a blinded, prospective fashion.
METHODS: Patients presenting at the emergency room within 6 h of symptom onset and a normal or nondiagnostic ECG were eligible. Dobutamine stress echocardiography was performed after unstable coronary artery disease was ruled out by a standard rule-out protocol and a negative serial troponin T; the occurrence of any new wall motion abnormality was considered positive. Results were kept blinded. End points were cardiac death, myocardial infarction, rehospitalization for unstable angina or revascularization.
RESULTS: In total, 377 patients were included. There were 2 deaths, 2 myocardial infarctions, 8 rehospitalization for unstable angina, and 10 revascularizations at six-month follow-up. The end points occurred in 8/26 (30.8%) patients with a positive versus 14/351 (4.0%) patients with a negative DSE (odds ratio, 10.7; 95% confidence interval, 4.0 to 28.8; p < 0.0001). By multivariate analysis, DSE remained a predictor of end points (p < 0.0001).
CONCLUSIONS: A predischarge DSE had important, independent prognostic value in low-risk, troponin negative, chest pain patients.

PMID 12598071  J Am Coll Cardiol. 2003 Feb 19;41(4):596-602.
著者: Gigliola Bedetti, Emilio M Pasanisi, Giancarlo Tintori, Lucas Fonseca, Simone Tresoldi, Calogero Minneci, Zoltan Jambrik, Bruno Ghelarducci, Andres Orlandini, Eugenio Picano
雑誌名: Int J Cardiol. 2005 Jul 20;102(3):461-7. doi: 10.1016/j.ijcard.2004.05.058.
Abstract/Text BACKGROUND: Emergency room (ER) evaluation of patients with acute chest pain and non-diagnostic electrocardiography (ECG) remains a frequent and difficult problem.
AIM: To assess safety and prognostic implications of pharmacological stress echocardiography in the ER chest pain unit (CPU).
METHODS: A total of 552 patients (321 males, age 58+/-12.6 years) with acute chest pain, negative serial enzymes and/or troponin, and ECG recordings, and normal/unchanged resting left ventricular function were prospectively enrolled and underwent pharmacological (dipyridamole or dobutamine) stress echo. Six echo labs that had passed the preliminary quality control for stress echo reading entered the study. Follow-up was obtained in all patients after a median period of 13 months.
RESULTS: No significant adverse events were observed during the test. Stress echocardiography was negative in 502 patients (91%) and positive in 50 (9%). The 502 patients with negative stress echocardiography were discharged with no or unchanged anti-ischemic medications. While the 50 patients with positive stress echo were admitted to the coronary care unit, 44 of these underwent coronary angiography with the result that 42 out of 44 showed significant coronary artery disease. There were 45 events in the follow-up: six in the 502 patients with negative and 39 in the 50 patients with positive stress echo (1.2% vs. 78%, p<0.001). The negative predictive value of stress echocardiography was 98.8% for all events and 99.6% for hard events.
CONCLUSIONS: Stress echocardiography is a feasible, safe, and effective tool for early stratification of patients admitted to the ER with acute chest pain and non-ischemic ECG and resting echo.

PMID 16004892  Int J Cardiol. 2005 Jul 20;102(3):461-7. doi: 10.1016/j・・・
著者: J A Trippi, K S Lee, G Kopp, D R Nelson, K G Yee, W H Cordell
雑誌名: J Am Coll Cardiol. 1997 Sep;30(3):627-32.
Abstract/Text OBJECTIVES: The practically and accuracy of dobutamine stress tele-echocardiography (DSTE) were assessed in patients presenting to the emergency department with chest pain.
BACKGROUND: Many patients evaluated for chest pain in the emergency department (ED) are admitted to the hospital needlessly because of the difficulty in differentiating noncardiac chest pain from myocardial ischemia.
METHODS: One hundred sixty-three patients with no evidence of myocardial infarction on initial blood studies or the electrocardiogram who were recommended for hospital admission to rule out myocardial infarction or myocardial ischemia were enrolled in this four-phase study. Rest echocardiography was performed in the ED, and the images were transmitted to a cardiologist for interpretation. If the results were normal, DSTE was then administered by a trained nurse. In the first three phases, all patients were admitted for observation regardless of the results of DSTE. In the fourth phase, those having normal DSTE results were able to be released.
RESULTS: The test was completed within an average of 5.4 h of presentation to the ED. The sensitivity and specificity of DSTE versus clinical and cardiac catheterization findings were 89.5% and 88.9%, respectively, with a negative predictive value for DSTE of 98.5%. Patients experienced frequent mild side effects (54.7%), but few (6.3%) caused the test to be discontinued prematurely. In phase 4 of the study, 72% of those slated for hospital admission because of cardiac risk factors and chest pain suggesting myocardial ischemia were discharged after normal DSTE results.
CONCLUSIONS: The use of DSTE in the evaluation of patients presenting with chest pain may improve screening for those who can be safely released from the ED.

PMID 9283518  J Am Coll Cardiol. 1997 Sep;30(3):627-32.
著者: M L Geleijnse, A Elhendy, J D Kasprzak, R Rambaldi, R T van Domburg, J H Cornel, A P Klootwijk, P M Fioretti, J R Roelandt, M L Simoons
雑誌名: Eur Heart J. 2000 Mar;21(5):397-406. doi: 10.1053/euhj.1999.1860.
Abstract/Text AIMS: To risk stratify and shorten hospital stay in patients with spontaneous (resting) chest pain and a non-diagnostic electrocardiogram (ECG).
METHODS AND RESULTS: The study comprised 102 patients (mean age 58+/-12 years, 67 men) with spontaneous chest pain and a non-diagnostic ECG. Forty-three patients had suspected coronary artery disease and 59 had known (but of unknown actual significance) coronary artery disease. All patients underwent serial creatine kinase enzyme measurements, continuous ECG monitoring for at least 12 h and early dobutamine-atropine stress echocardiography in patients with negative creatine kinase enzymes and normal findings at ECG monitoring. Dobutamine-atropine stress echocardiography was considered positive in patients with new or worsening wall thickening abnormalities. Patients with negative dobutamine-atropine stress echocardiography were discharged after the test. In-hospital and 6 month follow-up events noted were cardiac death, non-fatal myocardial infarction, unstable angina, and coronary artery bypass surgery or angioplasty. Thirteen patients had evidence of evolving myocardial infarction by elevated creatine kinase enzymes, or unstable angina by ECG monitoring. In the remaining 89 patients, dobutamine-atropine stress echocardiography was performed after a median observation period of 31 h (range 12-68 h). During dobutamine-atropine stress echocardiography no serious complications (death, non-fatal myocardial infarction, sustained ventricular tachycardia or ventricular fibrillation) occurred. Dobutamine-atropine stress echocardiography results were of poor quality in three, non-diagnostic in six, negative in 44 and positive in 36 patients. In the 80 patients with diagnostic dobutamine-atropine stress echocardiography, variables associated with in-hospital events (n=7) were history of exertional angina (P<0. 005), chest pain score (P<0.005), stress-induced angina (P<0.001) and positive dobutamine-atropine stress echocardiography (P<0.005). Variables associated with follow-up events (n=11) were history of exertional angina (P<0.05), chest pain score (P<0.001), stress-induced angina (P<0.01) and positive dobutamine-atropine stress echocardiography (P<0.01). At multivariate analysis the only significant predictor of events was positive dobutamine-atropine stress echocardiography (P<0.01).
CONCLUSION: Early dobutamine-atropine stress echocardiography may safely distinguish between low- and high-risk subsets for subsequent cardiac events in patients with spontaneous chest pain and a non-diagnostic ECG.

Copyright 2000 The European Society of Cardiology.
PMID 10666354  Eur Heart J. 2000 Mar;21(5):397-406. doi: 10.1053/euhj.・・・
著者: A Orlandini, E Tuero, E Paolasso, O G Vilamajó, R Díaz
雑誌名: Am J Cardiol. 2000 Dec 1;86(11):1247-50, A6.
Abstract/Text We tested the value of a stress echocardiography-based algorithm used in a chest pain center. The algorithm had superlative negative predictive value for cardiac events, allowing an early discharge.

PMID 11090800  Am J Cardiol. 2000 Dec 1;86(11):1247-50, A6.
著者: H Ito, T Tomooka, N Sakai, H Yu, Y Higashino, K Fujii, T Masuyama, A Kitabatake, T Minamino
雑誌名: Circulation. 1992 May;85(5):1699-705.
Abstract/Text BACKGROUND: We investigated myocardial perfusion dynamics after thrombolysis and its clinical implications.
METHODS AND RESULTS: We studied 39 patients with acute anterior myocardial infarction (AMI). Myocardial contrast echocardiography (MCE) was performed before and immediately after successful reflow with intracoronary injection of sonicated Ioxaglate. The average segmental score by two-dimensional echocardiography (graded 0, normal, to 3, akinetic/dyskinetic) and global ejection fraction (left ventricular ejection fraction, LVEF%) by left ventriculography were measured at 1 day and at 4 weeks after reflow. Hypokinesis in the infarct region was assessed by the centerline method and expressed in terms of standard deviations (regional wall motion [RWM]: SD/chord) of normal. Immediately after reflow, 30 of 39 patients (group A) showed significant contrast enhancement within the risk area. The other nine patients (23%, group B), however, showed the residual contrast defect in the risk area (myocardial no reflow). There were no significant differences in the elapsed time, angiographic collateral grade, and degree of residual stenosis between group A and group B. Before reflow, both groups exhibited similar levels of global and regional left ventricular function. Improvement in global (LVEF, average segmental score) and regional left ventricular function was greater in group A than in group B (average segmental score, 0.44 +/- 0.41 versus 0.97 +/- 0.36, p less than 0.01; LVEF, 56.4 +/- 13.4 versus 42.7 +/- 8.9, p less than 0.05; RWM, -1.87 +/- 0.85 versus -3.18 +/- 0.52, p less than 0.005).
CONCLUSIONS: MCE demonstrates that angiographically successful reflow cannot be used as an indicator of successful myocardial reperfusion in AMI patients. The residual contrast defect in the risk area demonstrated immediately after reflow is a predictor of poor functional recovery of the postischemic myocardium.

PMID 1572028  Circulation. 1992 May;85(5):1699-705.
著者: Khim Leng Tong, Sanjiv Kaul, Xin-Qun Wang, Diana Rinkevich, Saul Kalvaitis, Todd Belcik, Wolfgang Lepper, William A Foster, Kevin Wei
雑誌名: J Am Coll Cardiol. 2005 Sep 6;46(5):920-7. doi: 10.1016/j.jacc.2005.03.076.
Abstract/Text OBJECTIVES: We hypothesized that regional function (RF) and myocardial perfusion (MP) are superior to the Thrombolysis In Myocardial Infarction (TIMI) score for diagnosis and prognostication in patients presenting to the emergency department (ED) with chest pain (CP) and a nondiagnostic electrocardiogram.
BACKGROUND: Rapid diagnosis and prognostication is difficult in patients presenting to the ED with suspected cardiac CP.
METHODS: Contrast echocardiography was performed to assess RF and MP on 957 patients presenting to the ED with suspected cardiac CP and a nondiagnostic electrocardiogram. A modified TIMI (mTIMI) score was calculated from six immediately available variables. A full TIMI score also was derived after troponin levels were able to be accessed adequately. Follow-up was performed for early (within 24 h), intermediate (30 day), and late primary (death and myocardial infarction) or secondary (unstable angina and revascularization) events.
RESULTS: The mTIMI score was unable to discriminate between intermediate- compared to high-risk patients at any follow-up time point, whereas only 2 of 523 patients with normal RF had an early primary event. Regional function provided incremental prognostic value over mTIMI scores for predicting intermediate and late events. In patients with abnormal RF, MP further classified patients into intermediate- and high-risk groups. The full TIMI score could not improve upon these results at any follow-up time point.
CONCLUSIONS: Contrast echocardiography can rapidly and accurately provide short-, intermediate-, and long-term prognostic information in patients presenting to the ED with suspected cardiac CP even before serum cardiac markers are known. Integrating contrast echocardiography into the ED evaluation of CP may improve the risk stratification of such patients.

PMID 16139144  J Am Coll Cardiol. 2005 Sep 6;46(5):920-7. doi: 10.1016・・・
著者:
雑誌名: Lancet. 1999 Aug 28;354(9180):708-15.
Abstract/Text BACKGROUND: In unstable coronary-artery disease early invasive procedures are common, despite lack of evidence for the superiority of this approach. We compared an early invasive with a non-invasive treatment strategy in unstable coronary-artery disease.
METHODS: In a prospective randomised multicentre study, we randomly assigned 2457 patients in 58 Scandinavian hospitals (median age 66 years, 70% men) an early invasive or non-invasive treatment strategy with placebo-controlled long-term low-molecular-mass heparin (dalteparin) for 3 months. Coronary angiography was done within the first 7 days in 96% and 10%, and revascularisation within the first 10 days in 71% and 9% of patients in the invasive and non-invasive groups, respectively. We followed up patients for 6 months. Analysis was by intention to treat.
FINDINGS: After 6 months there was a decrease in the composite endpoint of death or myocardial infarction of 9.4% in the invasive group, compared with 12.1% in the non-invasive group (risk ratio 0.78 [95% CI 0.62-0.98], p=0.031). There was a significant decrease in myocardial infarction alone (7.8 vs 10.1%, 0.77 [0.60-0.99]; p=0.045) and non-significantly lower mortality (1.9 vs 2.9%, 0.65 [0.39-1.09]; p=0.10). Symptoms of angina and re-admission were halved by the invasive strategy. Results were independent of the randomised dalteparin treatment. The greatest advantages were seen in high-risk patients.
INTERPRETATION: The early invasive approach should be the preferred strategy in most patients with unstable coronary-artery disease who have signs of ischaemia on electrocardiography or raised biochemical markers of myocardial damage.

PMID 10475181  Lancet. 1999 Aug 28;354(9180):708-15.
著者: C P Cannon, W S Weintraub, L A Demopoulos, R Vicari, M J Frey, N Lakkis, F J Neumann, D H Robertson, P T DeLucca, P M DiBattiste, C M Gibson, E Braunwald, TACTICS (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy)--Thrombolysis in Myocardial Infarction 18 Investigators
雑誌名: N Engl J Med. 2001 Jun 21;344(25):1879-87. doi: 10.1056/NEJM200106213442501.
Abstract/Text BACKGROUND: There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation.
METHODS: We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months.
RESULTS: At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05).
CONCLUSIONS: In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients.

PMID 11419424  N Engl J Med. 2001 Jun 21;344(25):1879-87. doi: 10.1056・・・
著者: C P Cannon, W S Weintraub, L A Demopoulos, D H Robertson, G J Gormley, E Braunwald
雑誌名: Am J Cardiol. 1998 Sep 15;82(6):731-6.
Abstract/Text In the management of unstable angina and non-Q-wave acute myocardial infarction (AMI), there is considerable debate regarding the use of invasive strategy versus conservative strategy. The Thrombolysis In Myocardial Infarction (TIMI) III B trial found similar clinical outcomes for the 2 strategies, but the Veterans Administration Non-Q-Wave Infarction Strategies in-Hospital trial found a higher mortality with the invasive strategy. Both these trials were conducted before platelet glycoprotein IIb/IIIa inhibition and coronary stenting, both of which improve clinical outcome. Thus, there is a need to reexamine the question of which management strategy is optimal in the current era of platelet glycoprotein IIb/IIIa inhibition and new coronary interventions. The Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS-TIMI 18) trial is an international, multicenter, randomized trial that is evaluating the clinical efficacy of early invasive and early conservative treatment strategies in patients with unstable angina or non-Q-wave AMI treated with tirofiban, heparin, and aspirin. Patients are randomized to an invasive strategy, involving cardiac catheterization within 4 to 48 hours and revascularization with angioplasty or bypass surgery if feasible, versus a conservative strategy, where patients are referred for catheterization only for recurrent pain at rest or provokable ischemia. The primary end point is death, MI, or rehospitalization for acute coronary syndromes through a 6-month follow-up. The trial is also testing the "troponin hypothesis," that baseline troponins T and I will be useful in selecting an optimal management strategy.

PMID 9761082  Am J Cardiol. 1998 Sep 15;82(6):731-6.
著者: Bo Lagerqvist, Steen Husted, Fredrik Kontny, Elisabeth Ståhle, Eva Swahn, Lars Wallentin, Fast Revascularisation during InStability in Coronary artery disease (FRISC-II) Investigators
雑誌名: Lancet. 2006 Sep 16;368(9540):998-1004. doi: 10.1016/S0140-6736(06)69416-6.
Abstract/Text BACKGROUND: The FRISC-II invasive trial compared an early invasive with a non-invasive strategy in terms of death and myocardial infarction in non-ST-elevation acute coronary syndrome. We present 5-year follow-up results, overall and in subgroups based on recommended risk stratification criteria.
METHODS: In the FRISC-II trial, 2457 patients with non-ST-elevation acute coronary syndrome were randomised to early invasive strategy (coronary angiography and, if appropriate, revascularisation, within 7 days from admission) or non-invasive primarily medical strategy. Risk stratification was done on the basis of risk indicators at randomisation: age older than 65 years, male sex, diabetes mellitus, previous myocardial infarction, ST-segment depression, raised troponin concentration (>0.03 mug/L), and raised C-reactive protein or interleukin 6. Information on events after 24 months was taken from national registries. Analyses were done on an intention-to-treat basis.
FINDINGS: At 5 years the groups differed in terms of the primary composite endpoint of death, myocardial infarction, or both (invasive 217, 19.9 %; noninvasive 270, 24.5 %; risk ratio 0.81; 95% CI 0.69-0.95; p=0.009). 5-year mortality was 117 (9.7%) in the invasive group compared with 124 (10.1%) in the noninvasive group (0.95; 0.75 -1.21; p=0.693). Rates of myocardial infarction were 141 (12.9 %) in the invasive and 195 (17.7%) in the non-invasive group (0.73; 0.60-0.89; p=0.002). The benefit of the invasive strategy was confined to male patients, non-smokers, and patients with two or more risk indicators.
INTERPRETATION: The 5-year outcome of this trial indicates sustained benefit of an early invasive strategy in patients with non-ST-elevation acute coronary syndrome at moderate to high risk.

PMID 16980115  Lancet. 2006 Sep 16;368(9540):998-1004. doi: 10.1016/S0・・・
著者: K A A Fox, P Poole-Wilson, T C Clayton, R A Henderson, T R D Shaw, D J Wheatley, R Knight, S J Pocock
雑誌名: Lancet. 2005 Sep 10-16;366(9489):914-20. doi: 10.1016/S0140-6736(05)67222-4.
Abstract/Text BACKGROUND: The long-term outcome of an interventional strategy in patients with non-ST-elevation acute coronary syndrome is unknown. We tested whether an interventional strategy (routine angiography followed by revascularisation) was better than a conservative strategy (ischaemia-driven or symptom-driven angiography) over 5 years' follow-up.
METHODS: In a multicentre randomised trial, 1810 patients (from 45 hospitals in England and Scotland, UK) with non-ST-elevation acute coronary syndrome were randomly assigned to receive an early intervention (n=895) or a conservative strategy (n=915) within 48 h of the index episode of cardiac pain. In each group, the aim was to provide the best medical treatment, and also to undertake coronary arteriography within 72 h in the interventional strategy with subsequent management guided by the angiographic findings. Analysis was by intention to treat and the primary outcome (composite of death or non-fatal myocardial infarction) had masked independent adjudication. RITA 3 has been assigned the International Standard Randomised Control Trial Number ISRCTN07752711.
FINDINGS: At 1-year follow-up, rates of death or non-fatal myocardial infarction were similar. However, at a median of 5 years' follow-up (IQR 4.6-5.0), 142 (16.6%) patients with intervention treatment and 178 (20.0%) with conservative treatment died or had non-fatal myocardial infarction (odds ratio 0.78, 95% CI 0.61-0.99, p=0.044), with a similar benefit for cardiovascular death or myocardial infarction (0.74, 0.56-0.97, p=0.030). 234 (102 [12%] intervention, 132 [15%] conservative) patients died during follow-up (0.76, 0.58-1.00, p=0.054). The benefits of an intervention strategy were mainly seen in patients at high risk of death or myocardial infarction (p=0.004), and for the highest risk group, the odds ratio of death or non-fatal myocardial infarction was 0.44 (0.25-0.76).
INTERPRETATION: In patients with non-ST-elevation acute coronary syndrome, a routine invasive strategy leads to long-term reduction in risk of death or non-fatal myocardial infarction, and this benefit is mainly in high-risk patients. The findings provide support for national and international guidelines in the need for more robust risk stratification in acute coronary syndrome.

PMID 16154018  Lancet. 2005 Sep 10-16;366(9489):914-20. doi: 10.1016/S・・・
著者: Shamir R Mehta, Christopher P Cannon, Keith A A Fox, Lars Wallentin, William E Boden, Rudolf Spacek, Petr Widimsky, Peter A McCullough, David Hunt, Eugene Braunwald, Salim Yusuf
雑誌名: JAMA. 2005 Jun 15;293(23):2908-17. doi: 10.1001/jama.293.23.2908.
Abstract/Text CONTEXT: Patients with unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) can be cared for with a routine invasive strategy involving coronary angiography and revascularization or more conservatively with a selective invasive strategy in which only those with recurrent or inducible ischemia are referred for acute intervention.
OBJECTIVE: To conduct a meta-analysis that compares benefits and risks of routine invasive vs selective invasive strategies.
DATA SOURCES: Randomized controlled trials identified through search of MEDLINE and the Cochrane databases (1970 through June 2004) and hand searching of cross-references from original articles and reviews.
STUDY SELECTION: Trials were included that involved patients with unstable angina or NSTEMI who received a routine invasive or a selective invasive strategy.
DATA EXTRACTION: Major outcomes of death and myocardial infarction (MI) occurring from initial hospitalization to the end of follow-up were extracted from published results of eligible trials.
DATA SYNTHESIS: A total of 7 trials (N = 9212 patients) were eligible. Overall, death or MI was reduced from 663 (14.4%) of 4604 patients in the selective invasive group to 561 (12.2%) of 4608 patients in the routine invasive group (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.72-0.93; P = .001). There was a nonsignificant trend toward fewer deaths (6.0% vs 5.5%; OR, 0.92; 95% CI, 0.77-1.09; P = .33) and a significant reduction in MI alone (9.4% vs 7.3%; OR, 0.75; 95% CI, 0.65-0.88; P<.001). Higher-risk patients with elevated cardiac biomarker levels at baseline benefited more from routine intervention, with no significant benefit observed in lower-risk patients with negative baseline marker levels. During the initial hospitalization, a routine invasive strategy was associated with a significantly higher early mortality (1.1% vs 1.8% for selective vs routine, respectively; OR, 1.60; 95% CI, 1.14-2.25; P = .007) and the composite of death or MI (3.8% vs 5.2%; OR, 1.36; 95% CI, 1.12-1.66; P = .002). But after discharge, the routine invasive strategy was associated with fewer subsequent deaths (4.9% vs 3.8%; OR, 0.76; 95% CI, 0.62-0.94; P = .01) and the composite of death or MI (11.0% vs 7.4%; OR, 0.64; 95% CI, 0.56-0.75; P<.001). At the end of follow-up, there was a 33% reduction in severe angina (14.0% vs 11.2%; OR, 0.77; 95% CI, 0.68-0.87; P<.001) and a 34% reduction in rehospitalization (41.3% vs 32.5%; OR, 0.66; 95% CI, 0.60-0.72; P<.001) with a routine invasive strategy.
CONCLUSIONS: A routine invasive strategy exceeded a selective invasive strategy in reducing MI, severe angina, and rehospitalization over a mean follow-up of 17 months. But routine intervention was associated with a higher early mortality hazard and a trend toward a mortality reduction at follow-up. Future strategies should explore ways to minimize the early hazard and enhance later benefits by focusing on higher-risk patients and optimizing timing of intervention and use of proven therapies.

PMID 15956636  JAMA. 2005 Jun 15;293(23):2908-17. doi: 10.1001/jama.29・・・
著者: Anthony A Bavry, Dharam J Kumbhani, Andrew N Rassi, Deepak L Bhatt, Arman T Askari
雑誌名: J Am Coll Cardiol. 2006 Oct 3;48(7):1319-25. doi: 10.1016/j.jacc.2006.06.050. Epub 2006 Sep 12.
Abstract/Text OBJECTIVES: This study sought to systematically determine whether early invasive therapy improves survival and reduces adverse cardiovascular events in the management of non-ST-segment elevation acute coronary syndromes.
BACKGROUND: Although early invasive therapy reduces recurrent unstable angina, the magnitude of benefit on other important adverse outcomes is unknown.
METHODS: Clinical trials that randomized non-ST-segment elevation acute coronary syndrome patients to early invasive therapy versus a more conservative approach were included for analysis.
RESULTS: In all there were 7 trials with 8,375 patients available for analysis. At a mean follow-up of 2 years, the incidence of all-cause mortality was 4.9% in the early invasive group, compared with 6.5% in the conservative group (risk ratio [RR] = 0.75, 95% confidence interval [CI] 0.63 to 0.90, p = 0.001), and at 1 month (RR = 0.82, 95% CI 0.50 to 1.34, p = 0.43). At 2 years of follow-up, the incidence of nonfatal myocardial infarction was 7.6% in the invasive group, versus 9.1% in the conservative group (RR = 0.83, 95% CI 0.72 to 0.96, p = 0.012), and at 1 month (RR = 0.93, 95% CI 0.73 to 1.19, p = 0.57). At a mean of 13 months of follow-up, there was a reduction in rehospitalization for unstable angina (RR = 0.69, 95% CI 0.65 to 0.74, p < 0.0001).
CONCLUSIONS: Managing non-ST-segment elevation acute coronary syndromes by early invasive therapy improves long-term survival and reduces late myocardial infarction and rehospitalization for unstable angina.

PMID 17010789  J Am Coll Cardiol. 2006 Oct 3;48(7):1319-25. doi: 10.10・・・
著者: Robbert J de Winter, Fons Windhausen, Jan Hein Cornel, Peter H J M Dunselman, Charles L Janus, Peter E F Bendermacher, H Rolf Michels, Gerard T Sanders, Jan G P Tijssen, Freek W A Verheugt, Invasive versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) Investigators
雑誌名: N Engl J Med. 2005 Sep 15;353(11):1095-104. doi: 10.1056/NEJMoa044259.
Abstract/Text BACKGROUND: Current guidelines recommend an early invasive strategy for patients who have acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level. However, randomized trials have not shown an overall reduction in mortality, and the reduction in the rate of myocardial infarction in previous trials has varied depending on the definition of myocardial infarction.
METHODS: We randomly assigned 1200 patients with acute coronary syndrome without ST-segment elevation who had chest pain, an elevated cardiac troponin T level (> or =0.03 mug per liter), and either electrocardiographic evidence of ischemia at admission or a documented history of coronary disease to an early invasive strategy or to a more conservative (selectively invasive) strategy. Patients received aspirin daily, enoxaparin for 48 hours, and abciximab at the time of percutaneous coronary intervention. The use of clopidogrel and intensive lipid-lowering therapy was recommended. The primary end point was a composite of death, nonfatal myocardial infarction, or rehospitalization for anginal symptoms within one year after randomization.
RESULTS: The estimated cumulative rate of the primary end point was 22.7 percent in the group assigned to early invasive management and 21.2 percent in the group assigned to selectively invasive management (relative risk, 1.07; 95 percent confidence interval, 0.87 to 1.33; P=0.33). The mortality rate was the same in the two groups (2.5 percent). Myocardial infarction was significantly more frequent in the group assigned to early invasive management (15.0 percent vs. 10.0 percent, P=0.005), but rehospitalization was less frequent in that group (7.4 percent vs. 10.9 percent, P=0.04).
CONCLUSIONS: We could not demonstrate that, given optimized medical therapy, an early invasive strategy was superior to a selectively invasive strategy in patients with acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level.

Copyright 2005 Massachusetts Medical Society.
PMID 16162880  N Engl J Med. 2005 Sep 15;353(11):1095-104. doi: 10.105・・・
著者: Keith A A Fox, Tim C Clayton, Peter Damman, Stuart J Pocock, Robbert J de Winter, Jan G P Tijssen, Bo Lagerqvist, Lars Wallentin, FIR Collaboration
雑誌名: J Am Coll Cardiol. 2010 Jun 1;55(22):2435-45. doi: 10.1016/j.jacc.2010.03.007. Epub 2010 Mar 30.
Abstract/Text OBJECTIVES: This study was designed to determine: 1) whether a routine invasive (RI) strategy reduces the long-term frequency of cardiovascular death or nonfatal myocardial infarction (MI) using a meta-analysis of individual patient data from all randomized studies with 5-year outcomes; and 2) whether the results are influenced by baseline risk.
BACKGROUND: Pooled analyses of randomized trials show early benefit of routine intervention, but long-term results are inconsistent. The differences may reflect differing trial design, adjunctive therapies, and/or limited power. This meta-analysis (n = 5,467 patients) is designed to determine whether outcomes are improved despite trial differences.
METHODS: Individual patient data, with 5-year outcomes, were obtained from FRISC-II (Fragmin and Fast Revascularization during Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Randomized Trial of a Conservative Treatment Strategy Versus an Interventional Treatment Strategy in Patients with Unstable Angina) trials for a collaborative meta-analysis. A Cox regression analysis was used for a multivariable risk model, and a simplified integer model was derived.
RESULTS: Over 5 years, 14.7% (389 of 2,721) of patients randomized to an RI strategy experienced cardiovascular death or nonfatal MI versus 17.9% (475 of 2,746) in the selective invasive (SI) strategy (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.71 to 0.93; p = 0.002). The most marked treatment effect was on MI (10.0% RI strategy vs. 12.9% SI strategy), and there were consistent trends for cardiovascular deaths (HR: 0.83, 95% CI: 0.68 to 1.01; p = 0.068) and all deaths (HR: 0.90, 95% CI: 0.77 to 1.05). There were 2.0% to 3.8% absolute reductions in cardiovascular death or MI in the low- and intermediate-risk groups and an 11.1% absolute risk reduction in highest-risk patients.
CONCLUSIONS: An RI strategy reduces long-term rates of cardiovascular death or MI and the largest absolute effect in seen in higher-risk patients.

PMID 20359842  J Am Coll Cardiol. 2010 Jun 1;55(22):2435-45. doi: 10.1・・・
著者: J W Kennedy
雑誌名: Cathet Cardiovasc Diagn. 1982;8(1):5-11.
Abstract/Text
PMID 7060118  Cathet Cardiovasc Diagn. 1982;8(1):5-11.
著者: Bernard De Bruyne, Nico H J Pijls, Bindu Kalesan, Emanuele Barbato, Pim A L Tonino, Zsolt Piroth, Nikola Jagic, Sven Möbius-Winkler, Sven Mobius-Winckler, Gilles Rioufol, Nils Witt, Petr Kala, Philip MacCarthy, Thomas Engström, Keith G Oldroyd, Kreton Mavromatis, Ganesh Manoharan, Peter Verlee, Ole Frobert, Nick Curzen, Jane B Johnson, Peter Jüni, William F Fearon, FAME 2 Trial Investigators
雑誌名: N Engl J Med. 2012 Sep 13;367(11):991-1001. doi: 10.1056/NEJMoa1205361. Epub 2012 Aug 27.
Abstract/Text BACKGROUND: The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.
METHODS: In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.
RESULTS: Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary end-point event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event.
CONCLUSIONS: In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.).

PMID 22924638  N Engl J Med. 2012 Sep 13;367(11):991-1001. doi: 10.105・・・
著者: A G Adelman, E A Cohen, B P Kimball, R Bonan, D R Ricci, J G Webb, L Laramee, G Barbeau, M Traboulsi, B N Corbett
雑誌名: N Engl J Med. 1993 Jul 22;329(4):228-33. doi: 10.1056/NEJM199307223290402.
Abstract/Text BACKGROUND: Restenosis is a major limitation of coronary angioplasty. Directional coronary atherectomy was developed with the expectation that it would provide better results than angioplasty, including a lower rate of restenosis. We undertook a randomized, multicenter trial to compare the rates of restenosis for atherectomy and angioplasty when used to treat lesions of the proximal left anterior descending coronary artery.
METHODS: Of 274 patients referred for first-time, non-surgical revascularization of lesions of the proximal left anterior descending coronary artery, 138 were randomly assigned to undergo atherectomy and 136 to undergo angioplasty; 257 of 265 eligible patients (97 percent) underwent follow-up angiography at a median of 5.9 months. Computer-assisted quantitative measurements of luminal dimensions were determined from the angiograms obtained before and immediately after the procedure and at follow-up. The primary end point of restenosis was defined as stenosis of more than 50 percent of the vessel's diameter at follow-up.
RESULTS: Quantitative analysis showed that the procedural success rate was higher in patients who underwent atherectomy than in those who had angioplasty (94 percent vs. 88 percent, P = 0.061); there was no significant difference in the frequency of major in-hospital complications (5 percent vs. 6 percent). At follow-up, the rate of restenosis was 46 percent after atherectomy and 43 percent after angioplasty (P = 0.71). Despite a larger initial gain in the minimal luminal diameter with atherectomy (mean [+/- SD], 1.45 +/- 0.47 vs. 1.16 +/- 0.44 mm; P < 0.001), there was a larger late loss (0.79 +/- 0.61 vs. 0.47 +/- 0.64 mm; P < 0.001), resulting in a similar minimal luminal diameter in the two groups at follow-up (1.55 +/- 0.60 vs. 1.61 +/- 0.68, P = 0.44). The clinical outcomes at six months were not significantly different between the two groups.
CONCLUSIONS: The role of atherectomy in percutaneous coronary revascularization remains to be fully defined. However, as compared with angioplasty, atherectomy did not result in better late angiographic or clinical outcomes in patients with lesions of the proximal left anterior descending coronary artery.

PMID 8316267  N Engl J Med. 1993 Jul 22;329(4):228-33. doi: 10.1056/N・・・
著者: D S Baim, D E Cutlip, S K Sharma, K K Ho, R Fortuna, T L Schreiber, R L Feldman, J Shani, C Senerchia, Y Zhang, A J Lansky, J J Popma, R E Kuntz
雑誌名: Circulation. 1998 Feb 3;97(4):322-31.
Abstract/Text BACKGROUND: Previous directional coronary atherectomy (DCA) trials have shown no significant reduction in angiographic restenosis, more in-hospital complications, and higher 1-year mortality than conventional balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA]). DCA, however, has subsequently evolved toward a more "optimal" technique (larger devices, more extensive tissue removal, and routine postdilation to obtain diameter stenosis <20%).
METHODS AND RESULTS: The Balloon vs Optimal Atherectomy Trial (BOAT) was conducted to evaluate whether optimal DCA provides short- and long-term benefits compared with balloon angioplasty. One thousand patients with single de novo, native vessel lesions were randomized to either DCA or PTCA at 37 participating centers. Lesion success was obtained in 99% versus 97% (P=.02) of patients to a final residual diameter stenosis of 15% versus 28% (P<.0001) for DCA and PTCA, respectively, the latter including stents in 9.3% of the patients. There was no increase in major complications (death, Q-wave myocardial infarction, or emergent coronary artery bypass graft surgery [2.8% versus 3.3%]), although creatine kinase-MB >3X normal was more common with DCA (16% versus 6%; P<.0001). Angiographic restudy (in 79.6% of eligible patients at 7.2+/-2.6 [median, 6.9] months) showed a significant reduction in the prespecified primary end point of angiographic restenosis by DCA (31.4% versus 39.8%; P=.016). Clinical follow-up to 1 year showed nonsignificant 13% to 17% reductions in the DCA arm of the study for mortality rate (0.6% versus 1.6%; P=.14), target-vessel revascularization (17.1% versus 19.7%; P=.33), target-site revascularization (15.3% versus 18.3%; P=.23), and target-vessel failure (death, Q-wave myocardial infarction, or target-vessel revascularization, 21.1% versus 24.8%; P=.17).
CONCLUSIONS: Optimal DCA provides significantly higher short-term success, lower residual stenosis, and lower angiographic restenosis than conventional PTCA, despite failing to reach statistical significance for reducing late clinical events compared with PTCA with stent backup.

PMID 9468205  Circulation. 1998 Feb 3;97(4):322-31.
著者: Helen Parise, Akiko Maehara, Gregg W Stone, Martin B Leon, Gary S Mintz
雑誌名: Am J Cardiol. 2011 Feb 1;107(3):374-82. doi: 10.1016/j.amjcard.2010.09.030.
Abstract/Text We conducted a formal meta-analysis of peer-reviewed, published, randomized studies comparing intravascular ultrasound (IVUS)-guidance and angiographic-guided bare metal stent implantation. A total of 8 studies were identified. Because the Balloon Equivalent to Stent (BEST) study was a noninferiority trial designed to compare 2 very different percutaneous coronary intervention strategies-IVUS-guided aggressive balloon angioplasty (with bail-out stenting) and angiographic-guided deliberate bare metal stent implantation-it was eliminated. An unadjusted random-effects meta-analysis was used to compare the IVUS-guided and non-IVUS-guided stenting in the 7 remaining studies. A total of 2,193 patients were randomized in 5 multicenter and 2 single-center studies. IVUS guidance was associated with a significantly larger postprocedure angiographic minimum lumen diameter. The mean difference was 0.12 mm (95% confidence interval [CI] 0.06 to 0.18, p <0.0001). IVUS guidance was also associated with a significantly lower rate of 6-month angiographic restenosis (22% vs 29%, odds ratio 0.64, 95% CI 0.42 to 0.96, p = 0.02), a significant reduction in the revascularization rate (13% vs 18%, odds ratio 0.66, 95% CI 0.48 to 0.91, p = 0.004), and overall major adverse cardiac events (19% vs. 23%, odds ratio 0.69, 95% CI 0.49 to 0.97, p = 0.03). However, no significant effect was seen for myocardial infarction (p = 0.51) or mortality (p = 0.18). In conclusion, IVUS guidance for bare metal stent implantation improved the acute procedural results (angiographic minimum lumen diameter) and thereby reduced angiographic restenosis and repeat revascularization and major adverse cardiac events, with a neutral effect on death and myocardial infarction during a follow-up period of 6 months to 2.5 years.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21257001  Am J Cardiol. 2011 Feb 1;107(3):374-82. doi: 10.1016/j.・・・
著者: Jung-Sun Kim, Myeong-Ki Hong, Young-Guk Ko, Donghoon Choi, Jung Han Yoon, Seung-Hyuk Choi, Joo-Yong Hahn, Hyeon-Cheol Gwon, Myung-Ho Jeong, Hyo-Soo Kim, In-Whan Seong, Joo-Young Yang, Seung Woon Rha, Seung-Jea Tahk, Ki Bae Seung, Seung-Jung Park, Yangsoo Jang
雑誌名: Am Heart J. 2011 Jan;161(1):180-7. doi: 10.1016/j.ahj.2010.10.002.
Abstract/Text BACKGROUND: although intravascular ultrasound (IVUS) has been widely used for complex lesions during coronary intervention, IVUS for stenting at bifurcation lesions has not been sufficiently assessed. The aim of this study was to investigate the impact of IVUS guidance on long-term clinical outcomes during drug-eluting stent (DES) implantation for bifurcation lesions.
METHODS: the Korean multicenter bifurcation registry listed 1,668 patients with non-left main de novo bifurcation lesions who underwent DES implantation between January 2004 and June 2006. Using propensity score matching with clinical and angiographic characteristics, 487 patients with IVUS guidance and 487 patients with angiography guidance were selected. The long-term clinical outcomes were compared between the 2 groups.
RESULTS: baseline clinical and angiographic characteristics were well matched and showed no significant differences between the 2 groups. Two-stent technique and final kissing ballooning angioplasty were more frequently performed in the IVUS-guided group. Maximal stent diameters at both the main vessel and the side branch were larger in the IVUS-guided group. Periprocedural creatine kinase-MB elevation (>3 times of upper normal limits) was frequently observed in the angiography-guided group. The incidence of death or myocardial infarction was significantly lower in the IVUS-guided group compared to the angiography-guided group (3.8% vs 7.8%, log rank test P = .03, hazard ratio 0.44, 95% CI 0.12-0.96, Cox model P = .04).
CONCLUSIONS: intravascular ultrasound guidance during DES implantation at bifurcation lesions may be helpful to improve long-term clinical outcomes by reducing the occurrence of death or myocardial infarction.

PMID 21167352  Am Heart J. 2011 Jan;161(1):180-7. doi: 10.1016/j.ahj.2・・・
著者: Probal Roy, Daniel H Steinberg, Steven J Sushinsky, Teruo Okabe, Tina L Pinto Slottow, Kimberly Kaneshige, Zhenyi Xue, Lowell F Satler, Kenneth M Kent, William O Suddath, Augusto D Pichard, Neil J Weissman, Joseph Lindsay, Ron Waksman
雑誌名: Eur Heart J. 2008 Aug;29(15):1851-7. doi: 10.1093/eurheartj/ehn249. Epub 2008 Jun 11.
Abstract/Text AIMS: To assess the impact on clinical outcomes of intravascular ultrasound (IVUS) guidance during drug-eluting stent (DES) implantation. IVUS guidance during percutaneous coronary intervention (PCI) has been demonstrated to be useful in optimizing stent deployment. However, it is not proved that routine use of IVUS guidance with DES implantation can prevent stent thrombosis or restenosis.
METHODS AND RESULTS: The clinical outcomes of 884 patients undergoing IVUS-guided intracoronary DES implantation from April 2003 to May 2006 were compared with the outcomes of a propensity-score matched population undergoing DES implantation with angiographic guidance alone. The primary endpoint of the study was definite stent thrombosis at 12 months. The secondary endpoint was major adverse cardiac events (MACE). After propensity-score matching, the two groups were well matched for clinical and angiographic characteristics. Patients undergoing IVUS-guided DES implantation underwent less direct stenting, more post-dilation, and had greater cutting balloon and rotational atherectomy use. At 30 days and at 12 months, a higher rate of definite stent thrombosis was seen in the No IVUS group (0.5 vs. 1.4%; P = 0.046) and (0.7 vs. 2.0%; P = 0.014), respectively. There were no major differences in late stent thrombosis and MACE (14.5 vs. 16.2%; P = 0.33) at 12 month follow-up between the groups. Rates of death and Q-wave myocardial infarction were similar, and there was no significant difference between groups in target vessel revascularization. However, a trend was seen in favour of the IVUS group in target lesion revascularization (5.1 vs. 7.2%; P = 0.07). IVUS guidance was an independent predictor of freedom from cumulative stent thrombosis at 12 months (adjusted HR 0.5, CI 0.1-0.8; P = 0.02).
CONCLUSION: IVUS guidance during DES implantation has the potential to influence treatment strategy and reduce both DES thrombosis and the need for repeat revascularization.

PMID 18550555  Eur Heart J. 2008 Aug;29(15):1851-7. doi: 10.1093/eurhe・・・
著者: Yoichi Inaba, Steven R Bergmann
雑誌名: J Nucl Cardiol. 2008 May-Jun;15(3):345-52. doi: 10.1016/j.nuclcard.2008.02.019. Epub 2008 Apr 16.
Abstract/Text BACKGROUND: beta-Methyl-p-[(123)I]-iodophenyl-pentadecanoic acid (BMIPP) imaging has been used extensively to detect coronary artery disease (CAD), primarily in Japan. However, the reported sensitivity and specificity vary considerably from study to study. This meta-analysis was conducted to summarize the evidence for the diagnostic accuracy of resting BMIPP imaging in the detection of CAD.
METHODS AND RESULTS: A MEDLINE search of the literature published through the end of 2006 was performed. Seven studies (528 patients) met the inclusion criteria. Using random-effects models, the overall sensitivity and specificity to detect CAD were 78% (95% confidence interval, 73% to 81%) and 84% (95% confidence interval, 77% to 89%), respectively. A significant threshold effect was identified among studies, which was expected given the between-study variability in study methodology. A summary receiver-operating characteristic curve yielded an asymmetric curve with an area under the curve of 0.91 (SE, 0.020), indicating excellent diagnostic performance.
CONCLUSIONS: Imaging with BMIPP at rest exhibits a moderate sensitivity and high specificity to detect CAD in patients with a high prevalence of CAD. Thus, this tracer may be of great value for patients with acute chest pain and those with relative contraindications to exercise or pharmacologic stress myocardial perfusion imaging (MPI).

PMID 18513641  J Nucl Cardiol. 2008 May-Jun;15(3):345-52. doi: 10.1016・・・
著者: P R Franken, P Dendale, F De Geeter, D Demoor, A Bossuyt, P Block
雑誌名: J Nucl Med. 1996 May;37(5):718-22.
Abstract/Text UNLABELLED: We determined the predictive value of combined beta-methyl iodophenyl pentadecanoic acid (BMIPP) and sestamibi scintigraphy for the functional outcome after myocardial infarction and compared the value of this approach with dobutamine echocardiography.
METHODS: Rest BMIPP, rest sestamibi and low-dose dobutamine echocardiographic studies were obtained in 18 patients 4 to 10 days after infarction (mean 6.7 +/- 2.0 days). Six months later, a rest echocardiographic study was performed to assess functional outcome.
RESULTS: Wall motion improved in 27/33 segments (82%) which showed mismatching but not in 19/21 segments (90%) with matched defects (p < 0.001). The accuracy of combined BMIPP and sestamibi SPECT in predicting segmental functional outcome was higher (85%) than that of sestamibi uptake alone (77%). Wall motion improved in 16/20 segments (80%) showing contractile reserve and not in 21/34 segments (63%) with the negative dobutamine test, giving an accuracy of 69% for dobutamine echocardiography. Combination of the two techniques resulted in higher positive (94%) and negative predictive values (94%).
CONCLUSION: Mismatching of BMIPP and sestamibi uptake is predictive for long-term functional recovery after acute myocardial infarction. In contrast, segments with matched defects contain only scar tissue. Combined BMIPP and sestamibi scintigraphy offers increased accuracy compared to dobutamine echocardiography.

PMID 8965133  J Nucl Med. 1996 May;37(5):718-22.
著者: Paul D Stein, Abdo Y Yaekoub, Fadi Matta, H Dirk Sostman
雑誌名: Am J Med. 2008 Aug;121(8):715-25. doi: 10.1016/j.amjmed.2008.02.039.
Abstract/Text PURPOSE: The purpose of this systematic review was to assess the accuracy of 64-slice CT coronary angiography for the diagnosis of coronary artery disease.
METHODS: We attempted to identify all published trials in all languages that used 64-slice CT to diagnose coronary artery disease. Results of 64-slice CT coronary angiography were compared with invasive coronary angiography or intravascular ultrasound.
RESULTS: Sensitivity of 64-slice CT for significant (> or =50%) stenosis, based on pooled data from all studies, was > or =90% in patient-based evaluations, named vessels, segments, and coronary artery bypass grafts, except the left circumflex (sensitivity 88%), distal segments (80%), and stents (88%). Specificity was 88% in patient-based evaluations, and > or =90% at individual sites. Positive predictive values for patient-based evaluations, left main coronary artery, and coronary artery bypass grafts ranged from 91% to 93%, but elsewhere ranged from 69% to 84%. Negative predictive values were 96% to 100%. Positive likelihood ratios for patient-based evaluations were 8.0 and, at specific sites, were > or =9.7. Negative likelihood ratios, except for distal segments, were <0.1.
CONCLUSION: Negative 64-slice CT reliably excluded significant coronary disease. However, the data suggest that stenoses shown on 64-slice CT require confirmation. Combining the results of 64-slice CT with a pre-CT clinical probability assessment would strengthen the diagnosis. Due to the risk of radiation-induced cancer, patients should be selected carefully for this test, and scan protocols should be optimized to minimize risk.

PMID 18691486  Am J Med. 2008 Aug;121(8):715-25. doi: 10.1016/j.amjmed・・・
著者: Matthew J Budoff, David Dowe, James G Jollis, Michael Gitter, John Sutherland, Edward Halamert, Markus Scherer, Raye Bellinger, Arthur Martin, Robert Benton, Augustin Delago, James K Min
雑誌名: J Am Coll Cardiol. 2008 Nov 18;52(21):1724-32. doi: 10.1016/j.jacc.2008.07.031.
Abstract/Text OBJECTIVES: The purpose of this study was to evaluate the diagnostic accuracy of electrocardiographically gated 64-multidetector row coronary computed tomographic angiography (CCTA) in individuals without known coronary artery disease (CAD).
BACKGROUND: CCTA is a promising method for detection and exclusion of obstructive coronary artery stenosis. To date, no prospective multicenter trial has evaluated the diagnostic accuracy of 64-multidetector row CCTA in populations with intermediate prevalence of CAD.
METHODS: We prospectively evaluated subjects with chest pain at 16 sites who were clinically referred for invasive coronary angiography (ICA). CCTAs were scored by consensus of 3 independent blinded readers. The ICAs were evaluated for coronary stenosis based on quantitative coronary angiography (QCA). No subjects were excluded for baseline coronary artery calcium score or body mass index.
RESULTS: A total of 230 subjects underwent both CCTA and ICA (59.1% male; mean age: 57 +/- 10 years). On a patient-based model, the sensitivity, specificity, and positive and negative predictive values to detect > or =50% or > or =70% stenosis were 95%, 83%, 64%, and 99%, respectively, and 94%, 83%, 48%, 99%, respectively. No differences in sensitivity and specificity were noted for nonobese compared with obese subjects or for heart rates < or =65 beats/min compared with >65 beats/min, whereas calcium scores >400 reduced specificity significantly.
CONCLUSIONS: In this prospective multicenter trial of chest pain patients without known CAD, 64-multidetector row CCTA possesses high diagnostic accuracy for detection of obstructive coronary stenosis at both thresholds of 50% and 70% stenosis. Importantly, the 99% negative predictive value at the patient and vessel level establishes CCTA as an effective noninvasive alternative to ICA to rule out obstructive coronary artery stenosis. (A Study of Computed Tomography [CT] for Evaluation of Coronary Artery Blockages in Typical or Atypical Chest Pain; NCT00348569).

PMID 19007693  J Am Coll Cardiol. 2008 Nov 18;52(21):1724-32. doi: 10.・・・
著者: Julie M Miller, Carlos E Rochitte, Marc Dewey, Armin Arbab-Zadeh, Hiroyuki Niinuma, Ilan Gottlieb, Narinder Paul, Melvin E Clouse, Edward P Shapiro, John Hoe, Albert C Lardo, David E Bush, Albert de Roos, Christopher Cox, Jeffery Brinker, João A C Lima
雑誌名: N Engl J Med. 2008 Nov 27;359(22):2324-36. doi: 10.1056/NEJMoa0806576.
Abstract/Text BACKGROUND: The accuracy of multidetector computed tomographic (CT) angiography involving 64 detectors has not been well established.
METHODS: We conducted a multicenter study to examine the accuracy of 64-row, 0.5-mm multidetector CT angiography as compared with conventional coronary angiography in patients with suspected coronary artery disease. Nine centers enrolled patients who underwent calcium scoring and multidetector CT angiography before conventional coronary angiography. In 291 patients with calcium scores of 600 or less, segments 1.5 mm or more in diameter were analyzed by means of CT and conventional angiography at independent core laboratories. Stenoses of 50% or more were considered obstructive. The area under the receiver-operating-characteristic curve (AUC) was used to evaluate diagnostic accuracy relative to that of conventional angiography and subsequent revascularization status, whereas disease severity was assessed with the use of the modified Duke Coronary Artery Disease Index.
RESULTS: A total of 56% of patients had obstructive coronary artery disease. The patient-based diagnostic accuracy of quantitative CT angiography for detecting or ruling out stenoses of 50% or more according to conventional angiography revealed an AUC of 0.93 (95% confidence interval [CI], 0.90 to 0.96), with a sensitivity of 85% (95% CI, 79 to 90), a specificity of 90% (95% CI, 83 to 94), a positive predictive value of 91% (95% CI, 86 to 95), and a negative predictive value of 83% (95% CI, 75 to 89). CT angiography was similar to conventional angiography in its ability to identify patients who subsequently underwent revascularization: the AUC was 0.84 (95% CI, 0.79 to 0.88) for multidetector CT angiography and 0.82 (95% CI, 0.77 to 0.86) for conventional angiography. A per-vessel analysis of 866 vessels yielded an AUC of 0.91 (95% CI, 0.88 to 0.93). Disease severity ascertained by CT and conventional angiography was well correlated (r=0.81; 95% CI, 0.76 to 0.84). Two patients had important reactions to contrast medium after CT angiography.
CONCLUSIONS: Multidetector CT angiography accurately identifies the presence and severity of obstructive coronary artery disease and subsequent revascularization in symptomatic patients. The negative and positive predictive values indicate that multidetector CT angiography cannot replace conventional coronary angiography at present. (ClinicalTrials.gov number, NCT00738218.)

2008 Massachusetts Medical Society
PMID 19038879  N Engl J Med. 2008 Nov 27;359(22):2324-36. doi: 10.1056・・・
著者: Ronen Rubinshtein, David A Halon, Tamar Gaspar, Ronen Jaffe, Basheer Karkabi, Moshe Y Flugelman, Asia Kogan, Reuma Shapira, Nathan Peled, Basil S Lewis
雑誌名: Circulation. 2007 Apr 3;115(13):1762-8. doi: 10.1161/CIRCULATIONAHA.106.618389. Epub 2007 Mar 19.
Abstract/Text BACKGROUND: Multidetector computed tomography (MDCT) has high diagnostic value for detecting or excluding coronary artery stenosis. We examined performance characteristics of MDCT for diagnosing or excluding an acute coronary syndrome in patients presenting to the emergency department (ED) with possible ischemic chest pain and examined relation to clinical outcome during a 15-month follow-up period.
METHODS AND RESULTS: We prospectively studied 58 patients (56+/-10 years of age, 36% female) with chest pain possibly ischemic in origin and no new ECG changes or elevated biomarkers. The patients underwent 64-slice contrast-enhanced MDCT, which showed normal coronary vessels (no or trivial atheroma) in 15 patients, nonobstructive plaque in 20 (MDCT-negative patients), and obstructive coronary disease (> or = 50% luminal narrowing) in 23 (MDCT-positive group). By further investigation (new elevation of cardiac biomarkers, abnormal myocardial perfusion scintigraphy and/or invasive angiography), acute coronary syndrome was diagnosed in 20 of the 23 MDCT-positive patients (ED MDCT sensitivity 100% [20/20], specificity 92% [35/38], positive predictive value 87% [20/23], negative predictive value 100% [35/35]). During a 15-month follow-up period, no deaths or myocardial infarctions occurred in the 35 patients discharged from the ED after initial triage and MDCT findings. One patient underwent late percutaneous coronary intervention (late major adverse cardiovascular events rate, 2.8%). Overall, ED MDCT sensitivity for predicting major adverse cardiovascular events (death, myocardial infarction, or revascularization) during hospitalization and follow-up was 92% (12/13), specificity was 76% (34/45), positive predictive value was 52% (12/23), and negative predictive value was 97% (34/35).
CONCLUSIONS: We found that 64-slice cardiac MDCT is a potentially valuable diagnostic tool in ED patients with chest pain of uncertain origin, providing early direct noninvasive visualization of coronary anatomy. ED MDCT had high positive predictive value for diagnosing acute coronary syndrome, whereas a negative MDCT study predicted a low rate of major adverse cardiovascular events and favorable outcome during follow-up.

PMID 17372178  Circulation. 2007 Apr 3;115(13):1762-8. doi: 10.1161/CI・・・
著者: T H Lee, G W Rouan, M C Weisberg, D A Brand, D Acampora, C Stasiulewicz, J Walshon, G Terranova, L Gottlieb, B Goldstein-Wayne
雑誌名: Am J Cardiol. 1987 Aug 1;60(4):219-24.
Abstract/Text In a prospective multicenter investigation of emergency room patients with acute chest pain, physicians admitted 96% of patients with acute myocardial infarction (AMI) and discharged 4%. Of 35 patients who were sent home with AMI, only 11 (31%) returned to the same hospital because of persistent symptoms. Compared with a control group of 105 randomly selected patients with AMI who were admitted from the emergency room, patients in whom AMI was missed were significantly younger, had less typical symptoms and were less likely to to have had prior AMI or angina or to have electrocardiographic evidence of ischemia or infarction not known to be old. Despite the less typical presentations of patients in whom AMI was missed, after controlling for age and sex, the short-term mortality rate was significantly higher among patients in whom AMI was missed but in whom it was detected through our follow-up procedures than in admitted AMI patients. As determined by independent reviewers, 49% of the missed AMIs could have been diagnosed through improved electrocardiographic reading skills or by admission of patients with recognized ischemic pain at rest or ischemic electrocardiographic changes not known to be old.

PMID 3618483  Am J Cardiol. 1987 Aug 1;60(4):219-24.
著者: B D McCarthy, J R Beshansky, R B D'Agostino, H P Selker
雑誌名: Ann Emerg Med. 1993 Mar;22(3):579-82.
Abstract/Text STUDY OBJECTIVE: To determine the rate of missed acute myocardial infarction (AMI) in the emergency department and the factors related to missed diagnoses.
STUDY DESIGN: Observational and case-control study.
SETTING: Data were analyzed from a multicenter study of coronary care unit admitting practices that included patients who presented to the ED with chest pain or other symptoms suggestive of acute cardiac ischemia (N = 5,773). Patients with missed AMI (cases) were compared with control patients admitted with AMI and to a second control group of patients discharged without AMI.
RESULTS: Of 1,050 patients with AMI, 20 (1.9%; 95% confidence interval, 1.2-2.9%) were not admitted. Patients with missed AMI were significantly less likely to have ECG changes and a history of AMI or nitroglycerin use than patients admitted with AMI. However, they were significantly more likely to have ECG changes than patients discharged without AMI. Five patients with missed AMI (25%) had ST-segment elevation, and seven (35%) were discharged with a diagnosis of ischemic heart disease by the physician in the ED. Death or potentially lethal complications occurred in 25% of missed AMI patients.
CONCLUSION: The rate of missed AMI in the ED was only 1.9%. However, 25% of these might have been prevented had ST-elevation not been missed, and another 25% might have been prevented had patients who were recognized to have ischemic heart disease by the physician in the ED been admitted.

PMID 8442548  Ann Emerg Med. 1993 Mar;22(3):579-82.
著者: J H Pope, T P Aufderheide, R Ruthazer, R H Woolard, J A Feldman, J R Beshansky, J L Griffith, H P Selker
雑誌名: N Engl J Med. 2000 Apr 20;342(16):1163-70. doi: 10.1056/NEJM200004203421603.
Abstract/Text BACKGROUND: Discharging patients with acute myocardial infarction or unstable angina from the emergency department because of missed diagnoses can have dire consequences. We studied the incidence of, factors related to, and clinical outcomes of failure to hospitalize patients with acute cardiac ischemia.
METHODS: We analyzed clinical data from a multicenter, prospective clinical trial of all patients with chest pain or other symptoms suggesting acute cardiac ischemia who presented to the emergency departments of 10 U.S. hospitals.
RESULTS: Of 10,689 patients, 17 percent ultimately met the criteria for acute cardiac ischemia (8 percent had acute myocardial infarction and 9 percent had unstable angina), 6 percent had stable angina, 21 percent had other cardiac problems, and 55 percent had noncardiac problems. Among the 889 patients with acute myocardial infarction, 19 (2.1 percent) were mistakenly discharged from the emergency department (95 percent confidence interval, 1.1 to 3.1 percent); among the 966 patients with unstable angina, 22 (2.3 percent) were mistakenly discharged (95 percent confidence interval, 1.3 to 3.2 percent). Multivariable analysis showed that patients who presented to the emergency department with acute cardiac ischemia were more likely not to be hospitalized if they were women less than 55 years old (odds ratio for discharge, 6.7; 95 percent confidence interval, 1.4 to 32.5), were nonwhite (odds ratio, 2.2; 1.1 to 4.3), reported shortness of breath as their chief symptom (odds ratio, 2.7; 1.1 to 6.5), or had a normal or nondiagnostic electrocardiogram (odds ratio, 3.3; 1.7 to 6.3). Patients with acute infarction were more likely not to be hospitalized if they were nonwhite (odds ratio for discharge, 4.5; 95 percent confidence interval, 1.8 to 11.8) or had a normal or nondiagnostic electrocardiogram (odds ratio, 7.7; 95 percent confidence interval, 2.9 to 20.2). For the patients with acute infarction, the risk-adjusted mortality ratio for those who were not hospitalized, as compared with those who were, was 1.9 (95 percent confidence interval, 0.7 to 5.2), and for the patients with unstable angina, it was 1.7 (95 percent confidence interval, 0.2 to 17.0).
CONCLUSIONS: The percentage of patients who present to the emergency department with acute myocardial infarction or unstable angina who are not hospitalized is low, but the discharge of such patients is associated with increased mortality. Failure to hospitalize is related to race, sex, and the absence of typical features of cardiac ischemia. Continued efforts to reduce the number of missed diagnoses are warranted.

PMID 10770981  N Engl J Med. 2000 Apr 20;342(16):1163-70. doi: 10.1056・・・
著者: Richard Body, Gary Cook, Gillian Burrows, Simon Carley, Philip S Lewis
雑誌名: Emerg Med J. 2014 Nov;31(11):872-6. doi: 10.1136/emermed-2014-203832. Epub 2014 Jul 12.
Abstract/Text OBJECTIVE: To determine the diagnostic accuracy of emergency physician gestalt in emergency department (ED) patients with suspected cardiac chest pain, both alone and in combination with initial troponin level and ECG findings.
METHODS: We prospectively included patients presenting to the ED with suspected cardiac chest pain. Clinicians recorded their 'gestalt' at the time of presentation using a five-point Likert scale, blinded to outcome. Troponin T and high-sensitivity troponin T (hs-cTnT; both Roche Diagnostics Elecsys) levels were measured in admission blood samples. All patients underwent troponin testing at least 12 h after peak symptoms. The primary outcome was acute myocardial infarction (AMI).
RESULTS: 458 patients were included in this study, 81 (17.7%) of whom had AMI. Clinician gestalt alone had an area under the receiver operating characteristic curve of 0.76 (95% CI 0.70 to 0.82) for AMI. Immediately discharging patients with normal initial troponin and ECG in whom the clinician felt the diagnosis was 'probably not' or 'definitely not' acute coronary syndrome (ACS) would have avoided admission for 23.1% (95% CI 19% to 28%) patients with 100% sensitivity (95% CI 95.6% to 100%). With hs-cTnT, 100% sensitivity could have been achieved even if only patients with 'probable' or 'definite' ACS were investigated further, which would have allowed 41.7% patients to be discharged immediately.
CONCLUSIONS: Gestalt alone cannot be used to 'rule in' or 'rule out' ACS. By combining clinician gestalt with the admission ECG and troponin level, we found 100% sensitivity without the need for serial troponin testing. These findings have the potential to reduce unnecessary hospital admissions for suspected ACS but must be prospectively validated before considering clinical implementation.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
PMID 25016388  Emerg Med J. 2014 Nov;31(11):872-6. doi: 10.1136/emerme・・・
著者: F Nijland, O Kamp, A J Karreman, M J van Eenige, C A Visser
雑誌名: J Am Coll Cardiol. 1997 Dec;30(7):1618-24.
Abstract/Text OBJECTIVES: This study was designed to evaluate the relative prognostic significance of restrictive left ventricular (LV) filling after acute myocardial infarction.
BACKGROUND: Data regarding the contribution of diastolic dysfunction to prognosis after myocardial infarction are limited, and the additional value over the assessment of systolic dysfunction is not known.
METHODS: Serial Doppler echocardiography was performed in 95 patients on days 1, 3 and 7 and 3 months after acute myocardial infarction. Patients were classified into two groups: a restrictive group (n = 12) with a peak velocity of early diastolic filling wave (E)/peak velocity of late filling wave (A) ratio > or = 2 or between 1 and 2 and a deceleration time (DT) < or = 140 ms during at least one echocardiographic study; and a nonrestrictive group (n = 83) with an E/A ratio < or = 1 or between 1 and 2 and a DT > 140 ms at all examinations.
RESULTS: Cardiac death occurred in 10 patients during a mean follow-up interval of 32 +/- 17 months. The survival rate at 1 year was 100% in the nonrestrictive group and only 50% in the restrictive group. After 1 year there was a continuing divergence of mortality, resulting in a 3-year survival rate of 100% and 22%, respectively. Univariate Cox analysis revealed that restrictive LV filling, wall motion score index, ejection fraction and end-systolic and end-diastolic volume indexes, as well as peak creatine kinase, peak MB fraction and heart failure during the hospital course were significant predictors of cardiac death, although restrictive filling was the single best predictor (p < 0.0001). Multivariate analysis showed that restrictive filling adds prognostic information to clinical and echocardiographic variables of systolic dysfunction.
CONCLUSIONS: Restrictive LV filling after acute myocardial infarction is the single best predictor of cardiac death and adds significantly to clinical and echocardiographic markers of systolic dysfunction.

PMID 9385885  J Am Coll Cardiol. 1997 Dec;30(7):1618-24.
著者: J E Møller, E Søndergaard, S H Poulsen, K Egstrup
雑誌名: J Am Coll Cardiol. 2000 Nov 15;36(6):1841-6.
Abstract/Text OBJECTIVES: We sought to assess the prognostic value of left ventricular (LV) filling patterns, as determined by mitral E-wave deceleration time (DT) and color M-mode flow propagation velocity (Vp), on cardiac death and serial changes in LV volumes after a first myocardial infarction (MI).
BACKGROUND: Combined assessment of DT and Vp allows separation of the effects of compliance and relaxation on LV filling, thereby allowing identification of pseudonormal filling. This may be valuable after MI, where abnormal LV filling is frequently present.
METHODS: Echocardiography was performed within 24 h, five days and one and three months after MI in 125 unselected consecutive patients. Normal filling was defined as DT 140 to 240 ms and Vp > or =45 cm/s; impaired relaxation as DT > or =240 ms; pseudonormal filling as DT 140 to 240 ms and Vp <45 cm/s; and restrictive filling as DT <140 ms.
RESULTS: Left ventricular filling was normal in 38 patients; impaired relaxation in 38; pseudonormal in 23; and restrictive in 26. End-systolic and end-diastolic volume indexes were significantly increased during the first three months after MI in patients with pseudonormal or restrictive filling (37+/-15 vs. 47+/-19 ml/m2, p<0.0005 and 71+/-20 vs. 88+/-24 ml/m2, p<0.0005, respectively). During a follow-up period of 12+/-7 months, 33 patients died. Mortality was significantly higher in patients with impaired relaxation (p = 0.02), pseudonormal filling (p<0.00005) and restrictive filling (p<0.00005), compared with patients with normal filling. On Cox analysis, restrictive filling (p = 0.003), pseudonormal filling (p = 0.006) and Killip class > or =II (p = 0.008) independently predicted cardiac death, compared with clinical and echocardiographic variables.
CONCLUSIONS: Pseudonormal or restrictive filling patterns are related to progressive LV dilation and predict cardiac death after a first MI.

PMID 11092654  J Am Coll Cardiol. 2000 Nov 15;36(6):1841-6.
著者: Leonardo A M Zornoff, Hicham Skali, Marc A Pfeffer, Martin St John Sutton, Jean L Rouleau, Gervasio A Lamas, Ted Plappert, Jacques R Rouleau, Lemuel A Moyé, Sandra J Lewis, Eugene Braunwald, Scott D Solomon, SAVE Investigators
雑誌名: J Am Coll Cardiol. 2002 May 1;39(9):1450-5.
Abstract/Text OBJECTIVES: The aim of this study was to determine the prognostic value of right ventricular (RV) function in patients after a myocardial infarction (MI).
BACKGROUND: Right ventricular function has been shown to predict exercise capacity, autonomic imbalance and survival in patients with advanced heart failure (HF).
METHODS: Two-dimensional echocardiograms were obtained in 416 patients with left ventricular (LV) dysfunction (ejection fraction [LVEF] < or = 40%) from the Survival And Ventricular Enlargement (SAVE) echocardiographic substudy (mean 11.1 +/- 3.2 days post infarction). Right ventricular function from the apical four-chamber view, assessed as the percent change in the cavity area from end diastole to end systole (fractional area change [FAC]), was related to clinical outcome.
RESULTS: Right ventricular function correlated only weakly with the LVEF (r = 0.12, p = 0.013). On univariate analyses, the RV FAC was a predictor of mortality, cardiovascular mortality and HF (p < 0.0001 for all) but not recurrent MI. After adjusting for age, gender, diabetes mellitus, hypertension, previous MI, LVEF, infarct size, cigarette smoking and treatment assignment, RV function remained an independent predictor of total mortality, cardiovascular mortality and HF. Each 5% decrease in the RV FAC was associated with a 16% increased odds of cardiovascular mortality (95% confidence interval 4.3% to 29.2%; p = 0.006).
CONCLUSIONS: Right ventricular function is an independent predictor of death and the development of HF in patients with LV dysfunction after MI.

PMID 11985906  J Am Coll Cardiol. 2002 May 1;39(9):1450-5.
著者: Jacob E Moller, Graham S Hillis, Jae K Oh, James B Seward, Guy S Reeder, R Scott Wright, Seung W Park, Kent R Bailey, Patricia A Pellikka
雑誌名: Circulation. 2003 May 6;107(17):2207-12. doi: 10.1161/01.CIR.0000066318.21784.43. Epub 2003 Apr 14.
Abstract/Text BACKGROUND: After acute myocardial infarction (AMI), diastolic function assessed by Doppler echocardiography provides important prognostic information that is incremental to systolic function. However, Doppler variables are affected by multiple factors and may change rapidly. In contrast, left atrial (LA) volume is less influenced by acute changes and reflects subacute or chronic diastolic function. This may be of importance when one assesses risk in patients with AMI.
METHODS AND RESULTS: Three hundred fourteen patients with AMI who had a transthoracic echocardiogram with assessment of left ventricular (LV) systolic and diastolic function and measurement of LA volume during admission were identified. The LA volume was corrected for body surface area, and the population was divided according to LA volume index of 32 mL/m2 (2 SDs above normal). LA volume index was >32 mL/m2 in 142 (45%). The primary study end point was all-cause mortality. During follow-up of 15 (range 0 to 33) months, 46 patients (15%) died. LA volume index was a powerful predictor of mortality and remained an independent predictor (hazard ratio 1.05 per 1-mL/m2 change, 95% CI 1.03 to 1.06, P<0.001) after adjustment for clinical factors, LV systolic function, and Doppler-derived parameters of diastolic function.
CONCLUSIONS: Increased LA volume index is a powerful predictor of mortality after AMI and provides prognostic information incremental to clinical data and conventional measures of LV systolic and diastolic function.

PMID 12695291  Circulation. 2003 May 6;107(17):2207-12. doi: 10.1161/0・・・
著者: F Grigioni, M Enriquez-Sarano, K J Zehr, K R Bailey, A J Tajik
雑誌名: Circulation. 2001 Apr 3;103(13):1759-64.
Abstract/Text BACKGROUND: Myocardial infarction (MI) can directly cause ischemic mitral regurgitation (IMR), which has been touted as an indicator of poor prognosis in acute and early phases after MI. However, in the chronic post-MI phase, prognostic implications of IMR presence and degree are poorly defined.
METHODS AND RESULTS: We analyzed 303 patients with previous (>16 days) Q-wave MI by ECG who underwent transthoracic echocardiography: 194 with IMR quantitatively assessed in routine practice and 109 without IMR matched for baseline age (71+/-11 versus 70+/-9 years, P=0.20), sex, and ejection fraction (EF, 33+/-14% versus 34+/-11%, P=0.14). In IMR patients, regurgitant volume (RVol) and effective regurgitant orifice (ERO) area were 36+/-24 mL/beat and 21+/-12 mm(2), respectively. After 5 years, total mortality and cardiac mortality for patients with IMR (62+/-5% and 50+/-6%, respectively) were higher than for those without IMR (39+/-6% and 30+/-5%, respectively) (both P<0.001). In multivariate analysis, independently of all baseline characteristics, particularly age and EF, the adjusted relative risks of total and cardiac mortality associated with the presence of IMR (1.88, P=0.003 and 1.83, P=0.014, respectively) and quantified degree of IMR defined by RVol >/=30 mL (2.05, P=0.002 and 2.01, P=0.009) and by ERO >/=20 mm(2) (2.23, P=0.003 and 2.38, P=0.004) were high.
CONCLUSIONS: In the chronic phase after MI, IMR presence is associated with excess mortality independently of baseline characteristics and degree of ventricular dysfunction. The mortality risk is related directly to the degree of IMR as defined by ERO and RVol. Therefore, IMR detection and quantification provide major information for risk stratification and clinical decision making in the chronic post-MI phase.

PMID 11282907  Circulation. 2001 Apr 3;103(13):1759-64.
著者: Jacob E Møller, Graham S Hillis, Jae K Oh, Guy S Reeder, Bernard J Gersh, Patricia A Pellikka
雑誌名: Am Heart J. 2006 Feb;151(2):419-25. doi: 10.1016/j.ahj.2005.03.042.
Abstract/Text BACKGROUND: The prognostic importance of regional systolic function, as assessed by wall motion score index (WMSI), compared with global function, as assessed by left ventricular ejection fraction (LVEF), has not been assessed in large populations after acute myocardial infarction.
METHODS: Echocardiograms, including the assessment of WMSI and LVEF, were performed in 767 patients with acute myocardial infarction at a median of 1 day (25th and 75th percentiles 0-2 days) after admission. Patients were followed for a median of 19 months (range 12-28 months). Cox proportional hazards models were constructed for the primary study end point (all-cause mortality) and for a secondary end point (hospitalization for congestive heart failure).
RESULTS: During follow-up (median 40 months; range 32-50 months), 216 patients died and 54 patients were hospitalized for congestive heart failure. By univariate analysis, both LVEF (P < .0001) and WMSI (P < .0001) were powerful predictors of all-cause mortality. By a forward conditional Cox model, WMSI proved to be an independent predictor of death (hazard ratio 1.15 per 0.2-unit increase, 95% CI 1.10-1.21, P < .0001). When WMSI was included in the model, LVEF did not provide additional prognostic information (P = .77). Wall motion score index also proved to be an independent predictor of hospitalization for congestive heart failure (hazard ratio 1.21 per 0.2-unit increase, 95% CI 1.07-1.37, P = .002), whereas LVEF did not (P = .56).
CONCLUSION: Both LVEF and WMSI provide powerful prognostic information after acute myocardial infarction; however, the predictive power of WMSI is greater.

PMID 16442909  Am Heart J. 2006 Feb;151(2):419-25. doi: 10.1016/j.ahj.・・・
著者: Peter W Radke, Heribert Schunkert
雑誌名: Eur Heart J. 2010 Dec;31(24):2971-3. doi: 10.1093/eurheartj/ehq347. Epub 2010 Oct 12.
Abstract/Text
PMID 20943672  Eur Heart J. 2010 Dec;31(24):2971-3. doi: 10.1093/eurhe・・・
著者: J N Ruskin, J P DiMarco, H Garan
雑誌名: N Engl J Med. 1980 Sep 11;303(11):607-13. doi: 10.1056/NEJM198009113031103.
Abstract/Text We performed electrophysiologic studies in 31 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction. At the time of resuscitation, eight patients had sustained ventricular tachycardia and 23 patients had ventricular fibrillation. Programmed right ventricular stimulation later revealed electrically inducible ventricular arrhythmias in 25 of the 31 patients (81 per cent). Complete suppression of electrically inducible ventricular arrhythmias was achieved with antiarrhythmic therapy in 19 of these 25 patients. None of the 19 patients in whom the inducible arrhythmias was suppressed before discharge has died suddenly or had a symptomatic arrhythmia after a mean follow-up of 15 months (range, five to 26 months). Of the six patients in whom inducible arrhythmias could not be suppressed, three died suddenly (one in the hospital) within six months. We conclude that ventricular arrhythmias can be initiated and reproduced by programmed ventricular stimulation in a majority of patients who have been resuscitated after out-of-hospital cardiac arrest and that complete suppression of these arrhythmias with anti-arrhythmic therapy is highly predictive of survival for at least one year.

PMID 6772952  N Engl J Med. 1980 Sep 11;303(11):607-13. doi: 10.1056/・・・
著者: Marc S Sabatine, Carolyn H McCabe, David A Morrow, Robert P Giugliano, James A de Lemos, Marc Cohen, Elliott M Antman, Eugene Braunwald
雑誌名: Am Heart J. 2002 Jun;143(6):966-70.
Abstract/Text BACKGROUND: Patients with unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) remain at risk for death and cardiac ischemic events after being discharged from the hospital.
METHODS: We examined whether the Thrombolysis In Myocardial Infarction (TIMI) risk score for UA/NSTEMI, ascertained at presentation in patients enrolled in the TIMI 11B and Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI (ESSENCE) trials, could be used to identify patients at high risk for major cardiac events after hospital discharge.
RESULTS: There were a total of 1218 major cardiac events, defined as death, nonfatal myocardial infarction, or urgent revascularization, by day 43. Of these events, 336 (28%) occurred in patients after they were discharged from the hospital. Use of the TIMI risk score for UA/NSTEMI revealed a progressive, statistically significant increase in the rate of events after leaving the hospital as the patients' baseline level of risk increased (P <.001 for chi(2) test for trend). For patients with a risk score of 5 to 7, treatment with enoxaparin during the acute phase was associated with an odds ratio of 0.51 (95% CI 0.29-0.91) for the occurrence of death and cardiac ischemic events after hospital discharge.
CONCLUSIONS: More than one fourth of the major cardiac events that will occur in the first 6 weeks occur after discharge from the hospital. Stratification at presentation on the basis of the TIMI risk score for UA/NSTEMI can be used to identify patients at high risk for these events. Among patients at high-risk, acute-phase treatment with enoxaparin significantly reduces the risk of major cardiac events after leaving the hospital.

PMID 12075250  Am Heart J. 2002 Jun;143(6):966-70.
著者: Paul C Hébert, Dean A Fergusson
雑誌名: JAMA. 2004 Oct 6;292(13):1610-2. doi: 10.1001/jama.292.13.1610.
Abstract/Text
PMID 15467064  JAMA. 2004 Oct 6;292(13):1610-2. doi: 10.1001/jama.292.・・・
著者: J T Christenson, F Simonet, P Badel, M Schmuziger
雑誌名: Ann Thorac Surg. 1999 Sep;68(3):934-9.
Abstract/Text BACKGROUND: Beneficial effects of preoperative intraaortic balloon pump (IABP) treatment, on outcome and cost, in high-risk patients who have coronary artery bypass grafting have been demonstrated. We conducted a prospective, randomized study to determine the optimal timing for preoperative IABP support in a cohort of high-risk patients.
METHODS: Sixty consecutive high-risk patients who had coronary artery bypass grafting (presenting with two or more of the following criteria: left ventricular ejection fraction less than 0.30, unstable angina, reoperation, or left main stenosis greater than 70%) entered the study. Thirty patients did not receive preoperative IABP (controls), 30 patients had preoperative IABP therapy starting 2 hours (T2), 12 hours (T12), or 24 hours (T24), by random assignment, before the operation. Fifty patients had preoperative left ventricular ejection fraction mean, less than 0.30 (less than 0.26+/-0.08), (n = 40) unstable angina, 28% (n = 17) left main stenosis, and 32% (n = 19) were reoperations.
RESULTS: Cardiopulmonary bypass was shorter in the IABP groups. There was one death in the IABP group and six in the control group. The complication rate for IABP was 8.3% (n = 5) without group differences. Cardiac index was significantly higher postoperatively (p<0.001) in patients with preoperative IABP treatment compared with controls. There were no significant differences between the three IABP subgroups at any time. The incidence of postoperative low cardiac output was significantly lower in the IABP groups (p<0.001). Intubation time, length of stay in the intensive care unit and the hospital was shorter in the IABP groups (p = 0.211, p<0.001, and p = 0.002, respectively). There were no differences between the IABP subgroups in any of the studied variables.
CONCLUSIONS: The beneficial effect of preoperative IABP in high-risk patients who have coronary artery bypass grafting was confirmed. There were no differences in outcome between the subgroups; therefore, at 2 hours preoperatively, IABP therapy can be started.

PMID 10509987  Ann Thorac Surg. 1999 Sep;68(3):934-9.
著者: Deepak L Bhatt, Byron L Cryer, Charles F Contant, Marc Cohen, Angel Lanas, Thomas J Schnitzer, Thomas L Shook, Pablo Lapuerta, Mark A Goldsmith, Loren Laine, Benjamin M Scirica, Sabina A Murphy, Christopher P Cannon, COGENT Investigators
雑誌名: N Engl J Med. 2010 Nov 11;363(20):1909-17. doi: 10.1056/NEJMoa1007964. Epub 2010 Oct 6.
Abstract/Text BACKGROUND: Gastrointestinal complications are an important problem of antithrombotic therapy. Proton-pump inhibitors (PPIs) are believed to decrease the risk of such complications, though no randomized trial has proved this in patients receiving dual antiplatelet therapy. Recently, concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel.
METHODS: We randomly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo, in addition to aspirin. The primary gastrointestinal end point was a composite of overt or occult bleeding, symptomatic gastroduodenal ulcers or erosions, obstruction, or perforation. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, revascularization, or stroke. The trial was terminated prematurely when the sponsor lost financing.
RESULTS: We planned to enroll about 5000 patients; a total of 3873 were randomly assigned and 3761 were included in analyses. In all, 51 patients had a gastrointestinal event; the event rate was 1.1% with omeprazole and 2.9% with placebo at 180 days (hazard ratio with omeprazole, 0.34, 95% confidence interval [CI], 0.18 to 0.63; P<0.001). The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo (hazard ratio, 0.13; 95% CI, 0.03 to 0.56; P = 0.001). A total of 109 patients had a cardiovascular event, with event rates of 4.9% with omeprazole and 5.7% with placebo (hazard ratio with omeprazole, 0.99; 95% CI, 0.68 to 1.44; P = 0.96); high-risk subgroups did not show significant heterogeneity. The two groups did not differ significantly in the rate of serious adverse events, though the risk of diarrhea was increased with omeprazole.
CONCLUSIONS: Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI. (Funded by Cogentus Pharmaceuticals; ClinicalTrials.gov number, NCT00557921.).

PMID 20925534  N Engl J Med. 2010 Nov 11;363(20):1909-17. doi: 10.1056・・・
著者: Michelle L O'Donoghue, Eugene Braunwald, Elliott M Antman, Sabina A Murphy, Eric R Bates, Yoseph Rozenman, Alan D Michelson, Raymond W Hautvast, Peter N Ver Lee, Sandra L Close, Lei Shen, Jessica L Mega, Marc S Sabatine, Stephen D Wiviott
雑誌名: Lancet. 2009 Sep 19;374(9694):989-97. doi: 10.1016/S0140-6736(09)61525-7. Epub 2009 Aug 31.
Abstract/Text BACKGROUND: Proton-pump inhibitors (PPIs) are often prescribed in combination with thienopyridines. Conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use, measures of platelet function, and clinical outcomes for patients treated with clopidogrel or prasugrel.
METHODS: In the PRINCIPLE-TIMI 44 trial, the primary outcome was inhibition of platelet aggregation at 6 h assessed by light-transmission aggregometry. In the TRITON-TIMI 38 trial, the primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke. In both studies, PPI use was at physician's discretion. We used a multivariable Cox model with propensity score to assess the association of PPI use with clinical outcomes.
FINDINGS: In the PRINCIPLE-TIMI 44 trial, 201 patients undergoing elective percutaneous coronary intervention were randomly assigned to prasugrel (n=102) or high-dose clopidogrel (n=99). Mean inhibition of platelet aggregation was significantly lower for patients on a PPI than for those not on a PPI at 6 h after a 600 mg clopidogrel loading dose (23.2+/-19.5% vs 35.2+/-20.9%, p=0.02), whereas a more modest difference was seen with and without a PPI after a 60 mg loading dose of prasugrel (69.6+/-13.5% vs 76.7+/-12.4%, p=0.054). In the TRITON-TIMI 38 trial, 13,608 patients with an acute coronary syndrome were randomly assigned to prasugrel (n=6813) or clopidogrel (n=6795). In this study, 33% (n=4529) of patients were on a PPI at randomisation. No association existed between PPI use and risk of the primary endpoint for patients treated with clopidogrel (adjusted hazard ratio [HR] 0.94, 95% CI 0.80-1.11) or prasugrel (1.00, 0.84-1.20).
INTERPRETATION: The current findings do not support the need to avoid concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel or prasugrel.
FUNDING: Daiichi Sankyo Company Limited and Eli Lilly and Company sponsored the trials. This analysis had no funding.

PMID 19726078  Lancet. 2009 Sep 19;374(9694):989-97. doi: 10.1016/S014・・・
著者: E Ambrosioni, C Borghi, B Magnani
雑誌名: N Engl J Med. 1995 Jan 12;332(2):80-5. doi: 10.1056/NEJM199501123320203.
Abstract/Text BACKGROUND: Left ventricular dilatation and neuroendocrine activation are common after acute anterior myocardial infarction. Long-term treatment with an angiotensin-converting-enzyme (ACE) inhibitor may improve outcome by attenuating these processes. We investigated whether the ACE inhibitor zofenopril, administered for six weeks after anterior myocardial infarction, could improve both short-term and long-term outcome.
METHODS: A total of 1556 patients were enrolled within 24 hours after the onset of symptoms of acute anterior myocardial infarction, and they were randomly assigned in a double-blind fashion to receive either placebo (784 patients) or zofenopril (772 patients) for six weeks. At this time we assessed the incidence of death or severe congestive heart failure. The patients were reexamined after one year to assess survival.
RESULTS: The incidence of death or severe congestive heart failure at six weeks was significantly reduced in the zofenopril group (55 patients, 7.1 percent), as compared with the placebo group (83 patients, 10.6 percent); the cumulative reduction in the risk of death or severe congestive heart failure was 34 percent (95 percent confidence interval, 8 to 54 percent; P = 0.018). The reduction in risk was 46 percent (95 percent confidence interval, 11 to 71 percent; P = 0.018) for severe congestive heart failure and 25 percent (95 percent confidence interval, -11 to 60 percent; P = 0.19) for death. After one year of observation, the mortality rate was significantly lower in the zofenopril group (10.0 percent) than in the placebo group (14.1 percent); the reduction in risk was 29 percent (95 percent confidence interval, 6 to 51 percent; P = 0.011).
CONCLUSIONS: Treatment with zofenopril significantly improved both short-term and long-term outcome when this drug was started within 24 hours after the onset of acute anterior myocardial infarction and continued for six weeks.

PMID 7990904  N Engl J Med. 1995 Jan 12;332(2):80-5. doi: 10.1056/NEJ・・・
著者: P Søgaard, A Nøgaard, C O Gøtzsche, J Ravkilde, K Thygesen
雑誌名: Am Heart J. 1994 Jan;127(1):1-7.
Abstract/Text Treatment with angiotensin-converting enzyme inhibitors has a beneficial effect on myocardial ischemia and left ventricular dysfunction after myocardial infarction. The effect of captopril on myocardial ischemia was evaluated in 58 patients with left ventricular dysfunction (ejection fraction < 45%) after Q-wave or non-Q-wave myocardial infarction in a placebo-controlled, parallel, double-blind study. Patients were randomized on day 7 to either placebo or captopril (50 mg daily) and monitoring for a period of 180 days by serial echocardiography and ambulatory ST-segment monitoring. There was a significant effect of captopril on the duration of ambulatory ST depression during the 180 days: The values per day were reduced from 28 +/- 5 min at baseline to 2 +/- 1 min on day 180 in the Q-wave group (p < 0.01) and from 39 +/- 10 min at baseline to 6 +/- 1 min on day 180 in the non-Q-wave group (p < 0.05). In the placebo group the duration of ST depression on day 180 were 21 +/- 8 min in the Q-wave group and 22 +/- 7 min in the non-Q-wave group, thus being significantly higher as compared with the corresponding captopril groups (p < 0.01 and p < 0.05, respectively). In the placebo Q-wave group there was a significant increase in left ventricular end-diastolic volume index from 74 +/- 3.5 to 89 +/- 4.5 ml/m2 (p < 0.01) during the study period, which was in contrast to unchanged values of 75.5 +/- 3.0 and 75.0 +/- 3.5 ml/m2 (not significant [NS]) in the captopril Q-wave group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 8273728  Am Heart J. 1994 Jan;127(1):1-7.
著者: Faisal Shamshad, Satish Kenchaiah, Peter V Finn, Jordi Soler-Soler, John J V McMurray, Eric J Velazquez, Aldo P Maggioni, Robert M Califf, Karl Swedberg, Lars Kober, Yuri Belenkov, Sergei Varshavsky, Marc A Pfeffer, Scott D Solomon, VALsartan In Acute myocardial iNfarcTion (VALIANT) Trial Investigators
雑誌名: Am Heart J. 2010 Jul;160(1):145-51. doi: 10.1016/j.ahj.2010.02.037.
Abstract/Text BACKGROUND: Myocardial rupture is a relatively rare and usually fatal complication of myocardial infarction (MI). Early recognition of patients at greatest risk of myocardial rupture provides an opportunity for early intervention.
METHODS: VALIANT was a double-blind, randomized, controlled trial comparing valsartan, captopril, and their combination in high-risk patients post-MI. Myocardial rupture was identified by autopsy (available in 138/589 patients dying within 30 days of index MI), echocardiography, direct surgical visualization, or presence of hemopericardium. An independent clinical end points committee reviewed medical records for all deaths or suspected nonfatal cardiovascular events.
RESULTS: Rupture was identified in 45 (0.31%) patients enrolled in VALIANT, occurring 9.8 +/- 6.0 days after the qualifying MI. Rupture accounted for 7.6% (45/589) of all deaths occurring in the first 30 days of follow-up and 24% (33/138) of deaths in which autopsies were obtained. Compared with survivors, rupture was associated with increased age, hypertension, increased Killip class, lower estimated glomerular filtration rate, and Q wave MI, and inversely related to beta-blocker and diuretic use. Compared with patients who died of other causes within 30 days, patients with myocardial rupture were more likely to have had an inferior MI, Q wave MI, or hypertension; to have used oral anticoagulants; or to have received thrombolytic therapy.
CONCLUSIONS: Although rare, myocardial rupture accounted for nearly one fourth of all deaths within the first 30 days after high-risk MI, suggesting an estimated incidence of approximately 1% within the first 30 days. A number of clinical characteristics may identify post-MI patients at higher risk of myocardial rupture.

Copyright (c) 2010 Mosby, Inc. All rights reserved.
PMID 20598985  Am Heart J. 2010 Jul;160(1):145-51. doi: 10.1016/j.ahj.・・・
著者: Manesh R Patel, Trip J Meine, Lauren Lindblad, Jeffrey Griffin, Christopher B Granger, Richard C Becker, Frans Van de Werf, Harvey White, Robert M Califf, Robert A Harrington
雑誌名: Am Heart J. 2006 Feb;151(2):316-22. doi: 10.1016/j.ahj.2005.04.014.
Abstract/Text BACKGROUND: Cardiac tamponade is a life-threatening complication of acute myocardial infarction (MI). Data on the incidence, risk factors, and outcome of tamponade in patients with acute MI in the fibrinolytic era are limited.
METHODS: Data from a combined clinical trials database of ST-segment elevation MI were used to evaluate the incidence of cardiac tamponade, baseline characteristics, and outcomes in patients with and without tamponade. Univariable and multivariable analyses assessed the relationship between patient characteristics and tamponade development, and the influence of tamponade on mortality.
RESULTS: Of 102,060 patients, 865 (0.85%) developed isolated cardiac tamponade during initial hospitalization. Patients with tamponade were older (median 71.9 vs 61.6 years, P < .001), were more likely to be female (54.0% vs 25.1%, P < .001), were more likely to have an anterior MI (61.9% vs 41.5%, P < .001), and had a longer time from symptom onset to reperfusion (median 3.5 vs 2.8 hours, P < .001) than those without tamponade. Multivariable analyses identified increasing age, anterior MI location, female sex, and increased time from symptom onset to treatment as significant independent predictors of tamponade. Patients with tamponade had an increased death rate at 30 days (hazard ratio 7.9, 95% CI 4.7-13.5).
CONCLUSION: Cardiac tamponade occurs in < 1% of patients with fibrinolytic-treated acute MI and is associated with increased 30-day mortality. Time from symptom onset to treatment strongly predicted the development of tamponade, underscoring the need for continued efforts to increase speed to treatment in acute MI.

PMID 16442893  Am Heart J. 2006 Feb;151(2):316-22. doi: 10.1016/j.ahj.・・・
著者: A Purcaro, C Costantini, N Ciampani, M Mazzanti, C Silenzi, A Gili, R Belardinelli, D Astolfi
雑誌名: Am J Cardiol. 1997 Aug 15;80(4):397-405.
Abstract/Text In this prospective study we evaluated the value of the main diagnostic criteria for postinfarction subacute rupture of the ventricular free wall. Two-dimensional echocardiograms and recordings of right atrial pressure and waveform were immediately obtained in every patient exhibiting rapid clinical and/or hemodynamic compromise in the acute infarction setting. The same protocol was applied to patients referred from other hospitals for suspected myocardial rupture. In 28 cases a subacute free wall rupture was identified. In most of the patients the diagnosis was based on the demonstration of hemopericardium and cardiac tamponade by echocardiography, cardiac catheterization and, occasionally, by pericardiocentesis. In 2 instances, the identification of intrapericardial echo densities suggesting clots, in the absence of cardiac tamponade, allowed a diagnosis of subacute rupture. Direct, but indistinct visualization of myocardial rupture was obtained in 4 cases. Among the 28 patients with this complication, 4 died while awaiting surgery and 24 underwent surgical repair (mortality rate 33%). Long-term outcome of survivors was favorable. Various myocardial lesions underlie postinfarction subacute free wall rupture. Clinical presentation varied widely. The diagnosis was based, usually but not always, on the association of hemopericardium and signs of cardiac tamponade. An organized approach to management of this complication of acute myocardial infarction was suggested.

PMID 9285648  Am J Cardiol. 1997 Aug 15;80(4):397-405.
著者: K P Batts, D M Ackermann, W D Edwards
雑誌名: Hum Pathol. 1990 May;21(5):530-5.
Abstract/Text Among 100 consecutive autopsied cases of postinfarction rupture of the left ventricular free wall, 51% of the deaths were in-hospital and 49% were out of hospital. There were 51 men (mean age, 72 years) and 49 women (mean age, 76 years); 81% had multivessel disease. All had severe obstruction of at least one major epicardial coronary artery (98 atherosclerotic, one thrombotic, and one embolic). Acute coronary thrombosis was present in 73 cases and occurred on an atherosclerotic plaque in 72, 49 (68%) of which had associated plaque rupture. In 83 cases, the ruptured infarction represented the subject's first myocardial infarction. Despite a history of hypertension in 55 cases, appreciable left ventricular hypertrophy was observed in only 19 cases. By histopathologic age of infarction, 13 ruptures occurred during the first day, 45 between days 2 and 5, and 22 on days 6 and 7; thus, 58% occurred within 5 days and 80% within 7 days. The mid-ventricle was the most frequent site of rupture (66%). Ruptures most frequently involved the lateral aspect of the left ventricular free wall (44%). In 66 cases, the rupture tract occurred along the interface between viable and necrotic myocardium. Our findings support the observations of others that the risk factors for postinfarction left ventricular free wall rupture include age greater than 60 years, female gender, preexisting hypertension, absence of left ventricular hypertrophy, first myocardial infarction, and midventricular or lateral wall transmural infarctions.

PMID 2338333  Hum Pathol. 1990 May;21(5):530-5.
著者: P B Oliva, S C Hammill, W D Edwards
雑誌名: J Am Coll Cardiol. 1993 Sep;22(3):720-6.
Abstract/Text OBJECTIVE: To test the hypothesis that certain clinical events may precede free wall myocardial rupture and allow its prediction, we conducted a retrospective and prospective study of 70 patients with rupture.
BACKGROUND: Rupture of the left ventricular free wall develops in approximately 10% of patients with fatal acute transmural myocardial infarction. Clinically, its occurrence has been considered precipitous and unexpected. Pathologically, however, rupture appears to be a stuttering, progressive process characterized in many instances by an infiltrating intramural hemorrhage and a thrombus within the tear of > or = 1 day's duration.
METHODS: The clinical course and evolutionary electrocardiographic (ECG) changes in 70 consecutive patients with rupture and 100 comparison patients with acute myocardial infarction but without rupture were reviewed to ascertain whether certain clinical symptoms, signs and ECG alterations occur in patients prone to develop rupture, allowing its anticipation. In addition, a correlation was established between the site of infarction indicated by the ECG and the site of rupture determined at autopsy or surgery.
RESULTS: Patients with rupture had a significantly greater incidence of pericarditis, repetitive emesis and restlessness and agitation than did patients without rupture. More than 80% of patients with rupture had two or more symptoms compared with 3% of patients without rupture (p < 0.002). A deviation from the expected evolutionary T wave pattern occurred in 94% of patients with rupture and 34% of control patients (p < or = 0.02). An abrupt transient episode of hypotension and bradycardia, probably due to the initial tearing of the epicardium with a resultant small hemopericardium, was observed in 21% of patients with rupture. Rupture of the midlateral wall was most common (32%) and usually occurred in the setting of an inferoposterolateral infarction related to an acute left circumflex artery occlusion. On the basis of these clinical and ECG changes, rupture was confirmed by echocardiography and pericardiocentesis in the two most recent patients, and the defect was successfully repaired.
CONCLUSIONS: Rupture is often preceded by particular symptoms, signs--namely, one or more episodes of abrupt, transient hypotension and bradycardia and unexpected alterations of the T waves, especially directional changes of the latter. Patients displaying these symptoms, signs and ECG changes require a bedside echocardiogram and echocardiographically guided pericardiocentesis if fluid is visualized. If the pericardiocentesis identifies the fluid as blood, immediate surgery is indicated.

PMID 8354804  J Am Coll Cardiol. 1993 Sep;22(3):720-6.
著者: J López-Sendón, A González, E López de Sá, I Coma-Canella, I Roldán, F Domínguez, I Maqueda, L Martín Jadraque
雑誌名: J Am Coll Cardiol. 1992 May;19(6):1145-53.
Abstract/Text When ventricular free wall rupture after acute myocardial infarction is not followed by sudden death, it is referred to as subacute ventricular rupture. The sensitivity and specificity of clinical, hemodynamic and echocardiographic diagnostic variables obtained at bedside are unknown and were therefore prospectively studied in 1,247 consecutive patients with acute myocardial infarction including 33 patients with subacute ventricular rupture diagnosed at operation (group A) and 1,214 patients without ventricular rupture (at operation, postmortem study or at discharge) (group B). The incidence of syncope, recurrent chest pain, hypotension, electromechanical dissociation, cardiac tamponade, pericardial effusion, high acoustic intrapericardial echoes, right atrial and right ventricular wall compression identified in two-dimensional echocardiograms and hemopericardium demonstrated during pericardiocentesis was higher in group A than in group B (p less than 0.00001). The presence of cardiac tamponade, pericardial effusion greater than 5 mm, high density intrapericardial echoes or right atrial or right ventricular wall compression had a high diagnostic sensitivity (greater than or equal to 70%) and specificity (greater than 90%). The number of false positive diagnoses was always high for each diagnostic variable alone (greater than 20%), but the combination of clinical (hypotension), hemodynamic (cardiac tamponade) and echocardiographic variables allowed a sensitivity of greater than or equal to 65% with a small number of false positive diagnoses (less than 10%) and provided useful information for therapeutic decisions. The diagnosis of subacute ventricular rupture requires a surgical decision. Twenty-five (76%) of the 33 patients with subacute ventricular rupture survived the surgical procedure and 16 (48.5%) are long-term survivors. Thus, subacute ventricular wall rupture is a relatively frequent complication after acute myocardial infarction that can be accurately diagnosed and successfully treated.

PMID 1564213  J Am Coll Cardiol. 1992 May;19(6):1145-53.
著者: S Pohjola-Sintonen, J E Muller, P H Stone, S N Willich, E M Antman, V G Davis, C B Parker, E Braunwald
雑誌名: Am Heart J. 1989 Apr;117(4):809-18.
Abstract/Text Left ventricular rupture was studied in 849 patients enrolled in the Multicenter Investigation of Limitation of Infarct Size. Although documented rupture occurred in only 14 cases (1.7%), it accounted for 14% of in-hospital mortality. Seven of the 14 ruptures occurred within 2 days and 10 within 4 days of the MB-creatine kinase-determined onset of infarction. Three easily determined baseline characteristics defined a set of patients with a markedly increased risk of myocardial rupture. Rupture was 9.2 times more likely to occur in patients with all of the following characteristics than in the remaining patients: (1) no history of previous angina or myocardial infarction, (2) ST segment elevation or signs of Q wave development on the initial ECG, and (3) peak MB-creatine kinase value (greater than or equal to 150 IU/L). The risk of myocardial rupture with these three characteristics was 5.5%. Although these predictors are likely to be of little therapeutic value for free wall rupture, since most patients with that complication die within minutes of its onset, they may aid in alerting physicians to the early diagnosis and timely surgical correction of ventricular septal rupture.

PMID 2648779  Am Heart J. 1989 Apr;117(4):809-18.
著者: R C Becker, J S Hochman, C P Cannon, F A Spencer, S P Ball, M J Rizzo, E M Antman
雑誌名: J Am Coll Cardiol. 1999 Feb;33(2):479-87.
Abstract/Text OBJECTIVES: The purpose of this study was to determine the incidence and demographic characteristics of patients experiencing cardiac rupture after thrombolytic and adjunctive anticoagulant therapy and to identify possible associations between the mechanism of thrombin inhibition (indirect, direct) and the intensity of systemic anticoagulation with its occurrence. BACKGROUND Cardiac rupture is responsible for nearly 15% of all in-hospital deaths among patients with myocardial infarction (MI) given thrombolytic agents. Little is known about specific patient- and treatment-related risk factors. METHODS Patients (n = 3,759) with MI participating in the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9A and B trials received intravenous thrombolytic therapy, aspirin and either heparin (5,000 U bolus, 1,000 to 1,300 U/h infusion) or hirudin (0.1 to 0.6 mg/kg bolus, 0.1 to 0.2 mg/kg/h infusion) for at least 96 h. A diagnosis of cardiac rupture was made clinically in patients with sudden electromechanical dissociation in the absence of preceding congestive heart failure, slowly progressive hemodynamic compromise or malignant ventricular arrhythmias. RESULTS A total of 65 rupture events (1.7%) were reported-all were fatal, and a majority occurred within 48 h of treatment Patients with cardiac rupture were older, of lower body weight and stature and more likely to be female than those without rupture (all p < 0.001). By multivariable analysis, age >70 years (odds ratio [OR] 3.77; 95% confidence interval [CI] 2.06, 6.91), female gender (OR 2.87; 95% CI 1.44, 5.73) and prior angina (OR 1.82; 95% CI 1.05, 3.16) were independently associated with cardiac rupture. Independent predictors of nonrupture death included age >70 years (OR 3.68; 95% CI 2.53, 5.35) and prior MI (OR 2.14; 95%, CI 1.45, 3.17). There was no association between the type of thrombin inhibition, the intensity of anticoagulation and cardiac rapture. CONCLUSIONS Cardiac rupture following thrombolytic therapy tends to occur in older patients and may explain the disproportionately high mortality rate among women in prior dinical trials. Unlike major hemorrhagic complications, there is no evidence that the intensity of anticoagulation associated with heparin or hirudin administration influences the occurrence of rupture.

PMID 9973029  J Am Coll Cardiol. 1999 Feb;33(2):479-87.
著者: Raúl Moreno, José López-Sendón, Eulogio García, Leopoldo Pérez de Isla, Esteban López de Sá, Ana Ortega, Mar Moreno, Rafael Rubio, Javier Soriano, Manuel Abeytua, Miguel-Angel García-Fernández
雑誌名: J Am Coll Cardiol. 2002 Feb 20;39(4):598-603.
Abstract/Text OBJECTIVES: This study aimed to evaluate the effect of primary angioplasty (PA) over the risk of free wall rupture (FWR) in reperfused acute myocardial infarction (AMI).
BACKGROUND: It has been suggested that PA reduces the risk of FWR compared with thrombolysis. However, few studies have evaluated this issue, and there are no data demonstrating this hypothesis.
METHODS: A total of 1,375 patients with AMI treated with PA (n = 762, 55.4%) or thrombolysis (n = 613, 44.6%) within 12 h after symptoms onset were included. The diagnosis of FWR was made either in the presence of sudden death due to electromechanical dissociation with large pericardial effusion on an echocardiogram or when demonstrated post mortem or at surgery. A multivariable analysis was performed including type of reperfusion strategy.
RESULTS: The overall incidence of FWR was 2.5% (n = 34): 1.8% and 3.3% in patients treated with PA and with thrombolysis, respectively (p = 0.686). The following characteristics were associated with a higher rate of FWR in the univariable analysis: age >70 (5.2% vs. 1.2%, p < 0.001), female gender (5.1% vs. 1.8%, p = 0.006), anterior location (3.3% vs. 1.4%, p = 0.020) and treatment >2 h after symptoms onset (3.6% vs. 1.7%, p = 0.043). In the multivariable analysis, age >70 (odds ratio [OR]: 4.12, 95% confidence interval [CI]: 2.04 to 8.62, p < 0.001) and anterior location (OR: 2.91, 95% CI: 1.36 to 6.63, p = 0.008) were independent risk factors of FWR, whereas treatment with PA was an independent protective factor (OR: 0.46, 95% CI: 0.22 to 0.96, p = 0.0371).
CONCLUSIONS: In patients with AMI, PA reduces the risk of FWR in comparison with thrombolysis.

PMID 11849857  J Am Coll Cardiol. 2002 Feb 20;39(4):598-603.
著者: Jaume Figueras, Oscar Alcalde, José A Barrabés, Vicens Serra, Joan Alguersuari, Josefa Cortadellas, Rosa-Maria Lidón
雑誌名: Circulation. 2008 Dec 16;118(25):2783-9. doi: 10.1161/CIRCULATIONAHA.108.776690. Epub 2008 Dec 8.
Abstract/Text BACKGROUND: Possible changes in the incidence and outcome of cardiac rupture in patients with ST-elevation myocardial infarction over a long period of time have not been investigated.
METHODS AND RESULTS: The incidence of cardiac rupture in ST-elevation myocardial infarction patients and its mortality rate were investigated during a 30-year period divided into 5 intervals (1977 to 1982, 1983 to 1988, 1989 to 1994, 1995 to 2000, and 2001 to 2006). Of a total of 6678 consecutive patients, 425 experienced a free wall rupture (280 with cardiac tamponade: 227 with electromechanical dissociation and 53 with hypotension) or a septal rupture (145). After the exclusion of referrals from other centers (n=44), the incidence of definite cardiac rupture (septal rupture, anatomic evidence of free wall rupture, or electromechanical dissociation) declined progressively (6.2% in 1977 to 1982 to 3.2% in 2001 to 2006; P<0.001) in parallel with a progressive use of reperfusion therapy (0% to 75.1%; P<0.001). In addition, among patients with cardiac rupture, there was a progressive fall in the rate of death (94% to 75%; P<0.001) despite a trend toward increasing age (66+/-8 to 75+/-8 years; P<0.054) in conjunction with better control of systolic blood pressure at 24 hours (130+/-24 versus 110+/-18 mm Hg; P<0.001); an increased use of reperfusion therapy (0% to 59%; P<0.001), beta-blockers (0% to 45%; P<0.001), angiotensin-converting enzyme inhibitors (0% to 38%; P<0.001), and aspirin (0% to 96%; P<0.001); and a lower use of heparin (99% to 67%; P<0.001).
CONCLUSIONS: The decline in the incidence in cardiac rupture and its rate of death over the last 30 years appears to be associated with the increasing use of reperfusion strategies and adjunct medical therapy.

PMID 19064683  Circulation. 2008 Dec 16;118(25):2783-9. doi: 10.1161/C・・・
著者: Robert J Goldberg, Frederick A Spencer, Joel M Gore, Darleen Lessard, Jorge Yarzebski
雑誌名: Circulation. 2009 Mar 10;119(9):1211-9. doi: 10.1161/CIRCULATIONAHA.108.814947. Epub 2009 Feb 23.
Abstract/Text BACKGROUND: Limited information is available about potentially changing and contemporary trends in the incidence and hospital death rates of cardiogenic shock complicating acute myocardial infarction. The objectives of our study were to examine 3-decade-long trends (1975 to 2005) in the incidence rates of cardiogenic shock complicating acute myocardial infarction, patient characteristics and treatment practices associated with this clinical complication, and hospital death rates in residents of a large central New England community hospitalized with acute myocardial infarction at all area medical centers.
METHODS AND RESULTS: The study population consisted of 13 663 residents of the Worcester (Mass) metropolitan area hospitalized with acute myocardial infarction at all greater Worcester medical centers during 15 annual periods between 1975 and 2005. Overall, 6.6% of patients developed cardiogenic shock during their index hospitalization. The incidence rates of cardiogenic shock remained stable between 1975 and the late 1990s but declined in an inconsistent manner thereafter. Patients in whom cardiogenic shock developed had a significantly greater risk of dying during hospitalization (65.4%) than those who did not develop cardiogenic shock (10.6%) (P<0.001). Encouraging increases in hospital survival in patients with cardiogenic shock, however, were observed from the mid-1990s to our most recent study years. Several patient demographic and clinical characteristics were associated with an increased risk for developing cardiogenic shock.
CONCLUSIONS: Our findings indicate improving trends in the hospital prognosis associated with cardiogenic shock. Given the high death rates associated with this clinical complication, monitoring future trends in the incidence and death rates and the factors associated with an increased risk for developing cardiogenic shock remains warranted.

PMID 19237658  Circulation. 2009 Mar 10;119(9):1211-9. doi: 10.1161/CI・・・
著者: Patrick T O'Gara, Frederick G Kushner, Deborah D Ascheim, Donald E Casey, Mina K Chung, James A de Lemos, Steven M Ettinger, James C Fang, Francis M Fesmire, Barry A Franklin, Christopher B Granger, Harlan M Krumholz, Jane A Linderbaum, David A Morrow, L Kristin Newby, Joseph P Ornato, Narith Ou, Martha J Radford, Jacqueline E Tamis-Holland, Carl L Tommaso, Cynthia M Tracy, Y Joseph Woo, David X Zhao, Jeffrey L Anderson, Alice K Jacobs, Jonathan L Halperin, Nancy M Albert, Ralph G Brindis, Mark A Creager, David DeMets, Robert A Guyton, Judith S Hochman, Richard J Kovacs, Frederick G Kushner, E Magnus Ohman, William G Stevenson, Clyde W Yancy, American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
雑誌名: Circulation. 2013 Jan 29;127(4):e362-425. doi: 10.1161/CIR.0b013e3182742cf6. Epub 2012 Dec 17.
Abstract/Text
PMID 23247304  Circulation. 2013 Jan 29;127(4):e362-425. doi: 10.1161/・・・
著者: Peter J Gheeraert, Marc L De Buyzere, Yves M Taeymans, Thierry C Gillebert, Jose P S Henriques, Guy De Backer, Dirk De Bacquer
雑誌名: Eur Heart J. 2006 Nov;27(21):2499-510. doi: 10.1093/eurheartj/ehl218. Epub 2006 Sep 4.
Abstract/Text AIMS: To evaluate potential risk factors for primary ventricular fibrillation (PVF) during acute myocardial infarction (AMI) by a systematic review and meta-analyses.
METHODS AND RESULTS: We searched PubMed for English articles on 'humans' published between 1964 and January 2006 using a validated combination of MESH terms. Twenty-one cohort studies describing 57 158 patients with AMI were analysed. Patients with validated PVF (n=2316) were characterized by an earlier admission (weighted mean difference -2.62 h), male gender [odds ratio (OR 1.27)], smoking (OR 1.26), absence of history of angina (OR for history of angina 0.84), lower heart rate at admission (weighted mean difference -4.02 b.p.m.), ST-segment elevation on admission ECG (OR 3.35), AV conduction block before PVF (OR 2.02), and lower serum potassium at admission (weighted mean difference -0.27 meq/L). Patients with validated PVF developed a larger enzymatic infarct size (standardized mean difference 0.74, P<0.00001). PVF was not associated with a history of myocardial infarction or hypertension.
CONCLUSION: Patients who developed a validated PVF presented with characteristics of both abrupt coronary occlusion and early hospital admission. This review provides no evidence for risk factors for PVF other than ST-elevation and time from onset of symptoms. To find new risk factors, studies should compare validated PVF patients with non-PVF patients who have no signs of heart failure and comparable time delay between onset of symptoms and medical attendance.

PMID 16952926  Eur Heart J. 2006 Nov;27(21):2499-510. doi: 10.1093/eur・・・
著者: G H Tofler, P H Stone, J E Muller, J D Rutherford, S N Willich, N F Gustafson, W K Poole, B E Sobel, J T Willerson, T Robertson
雑誌名: Am J Cardiol. 1987 Oct 1;60(10):755-61.
Abstract/Text Previous studies have reached conflicting conclusions about whether cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation (VF) in acute myocardial infarction (AMI) is of long-term prognostic significance. The mortality rate in 849 patients with confirmed AMI was analyzed. The mortality rate during the initial hospitalization was higher for patients in whom VT/VF occurred (27% vs 7%, p less than 0.001). The in-hospital mortality rate for patients with primary VT/VF, that is, VT/VF occurring in the absence of hypotension or heart failure, was similar to that of patients who did not have VT/VF (8% vs 7%, difference not significant), whereas the rate for patients with secondary VT/VF was significantly greater than that for patients with no VT/VF (51% vs 7%, p less than 0.001). The timing of occurrence of VT/VF also influenced mortality: Patients in whom VT/VF occurred more than 72 hours after admission had a higher in-hospital mortality rate than did patients in whom it occurred within 72 hours (57% vs 20%, p less than 0.05). All cases of primary VT/VF occurred within the first 72 hours of admission. The long-term mortality rate for hospital survivors was not significantly different for patients who had had VT/VF during acute infarction compared with those who had not (19% vs 21%) (mean follow-up 32 months). Thus, cardiac arrest due to ventricular tachyarrhythmia was associated with a higher in-hospital mortality rate but was not a prognostic factor among hospital survivors. Patients resuscitated from primary VT/VF, which characteristically occurs early after AMI, do not have an adverse prognosis.

PMID 3661389  Am J Cardiol. 1987 Oct 1;60(10):755-61.
著者: A Volpi, A Maggioni, M G Franzosi, S Pampallona, F Mauri, G Tognoni
雑誌名: N Engl J Med. 1987 Jul 30;317(5):257-61. doi: 10.1056/NEJM198707303170501.
Abstract/Text The in-hospital prognosis of patients with acute myocardial infarction complicated by primary ventricular fibrillation has not been satisfactorily defined. We addressed this question by studying patients with primary ventricular fibrillation derived from a large study (11,712 patients) of intravenous streptokinase in the treatment of acute myocardial infarction. Ventricular fibrillation was considered to be primary when it complicated a first myocardial infarction not associated with heart failure or shock and occurred within 48 hours of hospital admission. The 332 patients with primary ventricular fibrillation represented an overall incidence of 2.8 percent. A significant excess of in-hospital deaths was found in the patients with primary ventricular fibrillation as compared with those in the reference group (10.8 percent vs. 5.9 percent; relative risk, 1.94; 95 percent confidence interval, 1.35 to 2.78). Thrombolytic treatment with intravenous streptokinase did not afford protection against primary ventricular fibrillation. We observed that being over 65 years old had a protective effect against primary ventricular fibrillation (relative risk, 0.6; 95 percent confidence interval, 0.45 to 0.80). Our data do not indicate whether primary ventricular fibrillation is simply a marker for patients at increased risk of death or a direct cause of the increase in mortality. Our results do show, however, that primary ventricular fibrillation occurring in a coronary care unit is a negative predictor of short-term survival in patients with acute myocardial infarction.

PMID 3600719  N Engl J Med. 1987 Jul 30;317(5):257-61. doi: 10.1056/N・・・
著者: S Behar, U Goldbourt, H Reicher-Reiss, E Kaplinsky
雑誌名: Am J Cardiol. 1990 Nov 15;66(17):1208-11.
Abstract/Text In 5,839 consecutive patients with acute myocardial infarction (AMI), hospitalized between July 1981 and July 1983 in 14 coronary care units in Israel, the incidence of primary ventricular fibrillation (VF) was 2.1%. Patients with primary VF resembled counterparts without VF in terms of age, gender, frequency of previous AMI and past cigarette smoking habits. The hospital course of patients with primary VF revealed increased incidence of primary atrial fibrillation and atrioventricular block. Increased serum levels of glutamic oxaloacetic transaminase and lactic dehydrogenase were noted among the patients with primary VF. In-hospital mortality rate was 18.8% in 122 patients with primary VF compared with 8.5% in 3,707 patients forming the reference group (p less than 0.01). Adjustment by age using logistic function yielded an estimate of 2.86 for relative mortality odds associated with primary VF, and further adjustment by gender, history of AMI, systemic hypertension, and by enzymatically estimated infarct size slightly reduced the estimated odds, at 2.52 (95% confidence interval, 1.42 to 4.46). Prognosis after discharge from the hospital was independent of primary VF. In conclusion, primary VF exerts an independent, significant effect on in-hospital mortality.

PMID 2239724  Am J Cardiol. 1990 Nov 15;66(17):1208-11.
著者: A Volpi, A Cavalli, M G Franzosi, A Maggioni, F Mauri, E Santoro, G Tognoni
雑誌名: Am J Cardiol. 1989 May 15;63(17):1174-8.
Abstract/Text The 1-year prognosis of 293 patients discharged alive from the hospital after acute myocardial infarction (AMI), who experienced primary ventricular fibrillation (VF) in the acute phase, was compared with that of a reference group of 6,337 patients identified from the same population included in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto miocardico (GISSI) trial. There was no difference in the 6- and 12-month mortality between the patients with primary VF and the reference group (3.7 vs 2.7% and 4.1 vs 4.2%, respectively). Survival of the 2 groups was also similar when patients were stratified according to infarct site (anterior and posterior), and whether or not they received treatment with streptokinase during AMI. Thus, long-term mortality of patients discharged alive after AMI complicated by primary VF is low and is not influenced by previous fibrinolytic therapy or by infarct site. The excess mortality of patients with primary VF is confined to the hospital phase, after which survivors represent a low-risk subgroup.

PMID 2565684  Am J Cardiol. 1989 May 15;63(17):1174-8.
著者: David C Burgess, Michael J Kilborn, Anthony C Keech
雑誌名: Eur Heart J. 2006 Dec;27(23):2846-57. doi: 10.1093/eurheartj/ehl272. Epub 2006 Oct 2.
Abstract/Text AIMS: Atrial fibrillation (AF) is the most common complication after cardiac surgery. We aimed to evaluate, by meta-analysis, all randomized trials testing interventions for preventing AF.
METHODS AND RESULTS: Ninety-four trials of prevention of post-operative AF were identified, by standard search methods, and analysed by standard meta-analysis techniques. All five commonly tested interventions, beta-blockers (BBs), sotalol, amiodarone, magnesium, and atrial pacing, were effective in preventing AF. The odds ratio (OR) for the effect of BB on the incidence of AF was 0.36 (95% CI 0.28-0.47, P<0.001), but after trials confounded by post-operative non-study BB withdrawal were excluded was 0.69 (95% CI 0.54-0.87, P=0.002). Sotalol reduced AF, compared with placebo (OR 0.34, 95% CI 0.26-0.45, P<0.001) and compared with conventional BB (OR 0.42, 95% CI 0.26-0.65, P<0.001). Amiodarone reduced AF (OR 0.48, 95% CI 0.40-0.57, P<0.001). Magnesium (Mg) also had an effect (OR 0.57 95% CI 0.42-0.77) but there was significant heterogeneity (P<0.001), partly explained by concomitant BB. The effect of Mg with BB was less (OR 0.83, 95% CI 0.60-1.16). Pacing reduced AF (OR 0.60, 95% CI 0.47-0.77, P<0.001), despite wide variations in techniques. Only amiodarone and pacing significantly reduced length of stay, average -0.60 days (95% CI -0.92 to -0.29) and -1.3 days (95% CI -2.55 to -0.08), respectively. Collectively, all treatments analysed together reduced stroke (OR 0.63, 95% CI 0.41-0.98). Amiodarone was the only intervention that alone significantly reduced stroke rate (OR 0.54, 95% CI 0.30-0.95).
CONCLUSION: All five interventions reduced the incidence of AF, though the effect of BBs is less than previously thought. The significant reductions in length of stay and stroke in meta-analysis suggest that there are worthwhile benefits from aggressive prevention. Larger studies to confirm these clinical benefits and evaluate their cost-effectiveness would be worthwhile.

PMID 17015402  Eur Heart J. 2006 Dec;27(23):2846-57. doi: 10.1093/eurh・・・
著者: Eugene Crystal, Stuart J Connolly, Khaled Sleik, Tracy J Ginger, Salim Yusuf
雑誌名: Circulation. 2002 Jul 2;106(1):75-80.
Abstract/Text BACKGROUND: Postoperative atrial fibrillation (AF) is a common complication of cardiac surgery and has been associated with increased incidence of other complications and increased hospital length of stay (LOS). Prevention of AF is a reasonable clinical goal, and, consequently, many randomized trials have evaluated the effectiveness of pharmacological and nonpharmacological interventions for prevention of AF. To better understand the role of various prophylactic therapies against postoperative AF, a systematic review of evidence from randomized trials was performed.
METHODS AND RESULTS: Fifty-two randomized trials (controlled by placebo or routine treatment) of beta-blockers, sotalol, amiodarone, or pacing were identified by systematic literature search. The 3 drug treatments each prevented AF with the following odds ratios (ORs): beta-blockers, 0.39 (95% CI, 0.28 to 0.52); sotalol, 0.35 (95% CI, 0.26 to 0.49); and amiodarone, 0.48 (95% CI, 0.37 to 0.61). Pacing was also effective; for biatrial pacing, the OR was 0.46 (95% CI, 0.30 to 0.71). The influence of pharmacological interventions on LOS was as follows: -0.66 day (95% CI, 2.04 to 0.72) for beta-blockers; -0.40 day (95% CI, 0.87 to 0.08) for sotalol; and -0.91 day (95% CI, 1.59 to -0.23) for amiodarone. The influence for biatrial pacing was -1.54 day (95% CI, -2.85 to -0.24). The incidence of stroke was 1.2% in all the treatment groups combined and 1.4% in controls (OR, 0.90; 95% CI, 0.46 to 1.74).
CONCLUSIONS: Beta-blockers, sotalol, and amiodarone all reduce risk of postoperative AF with no marked difference between them. There is evidence that use of these drugs will reduce LOS. Biatrial pacing is a promising new treatment opportunity. There was no evidence that reducing postoperative AF reduces stroke; however, data on stroke are incomplete.

PMID 12093773  Circulation. 2002 Jul 2;106(1):75-80.
著者: Sean M Bagshaw, P Diane Galbraith, L Brent Mitchell, Reg Sauve, Derek V Exner, William A Ghali
雑誌名: Ann Thorac Surg. 2006 Nov;82(5):1927-37. doi: 10.1016/j.athoracsur.2006.06.032.
Abstract/Text Amiodarone has been proposed to decrease atrial fibrillation after cardiac surgery. The literature was systematically reviewed for randomized trials comparing amiodarone with control for prevention of atrial fibrillation. Data were extracted on study characteristics, quality, and incidence of atrial fibrillation, cardiovascular outcomes, and length of hospitalization. Nineteen trials were included. Amiodarone reduced the odds ratio of atrial fibrillation (0.50; 95% confidence interval [CI]: 0.43 to 0.59, p < 0.0001), ventricular tachyarrhythmias (0.39; 95% CI: 0.26 to 0.58, p < 0.0001), and strokes (0.53; 95% CI: 0.30 to 0.92, p = 0.02). Amiodarone reduced hospital stay (0.6 days; 95% CI: 0.4 to 0.8, p < 0.0001). Amiodarone decreased atrial fibrillation, reduced perioperative ventricular tachyarrhythmias and strokes, and reduced duration of hospitalization. The current evidence supports recommending the routine use of perioperative amiodarone for cardiac surgery.

PMID 17062287  Ann Thorac Surg. 2006 Nov;82(5):1927-37. doi: 10.1016/j・・・
著者: M O'Doherty, D I Tayler, E Quinn, R Vincent, D A Chamberlain
雑誌名: Br Med J (Clin Res Ed). 1983 Apr 30;286(6375):1405-8.
Abstract/Text Of 2886 patients monitored during acute myocardial infarction, 500 were observed within one hour of the onset of symptoms. Half of the early admission group were admitted in response to emergency 999 calls and 435 of them travelled in resuscitation ambulances, where surveillance for arrhythmias was instituted. Pulmonary oedema occurred in 130 patients (26%), cardiogenic shock supervened in 60 (12%), and 115 (23%) died in hospital. Ventricular fibrillation was observed in 98 patients (20%). Forty two of them survived to be discharged, including 20 of the 24 with primary fibrillation which had occurred first in hospital. In only one case did primary ventricular fibrillation occur after the first 10 hours of onset of illness. Sinus bradycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation were all observed more frequently in patients admitted within one hour after the onset of symptoms than in those admitted later. An element of selection is inevitable when early admission is encouraged by the existence of a resuscitation ambulance system; this will depend in part on the early recognition of risk and the geographical location of the attack. These factors may bias the group towards relatively high risk. Nevertheless, prompt admission after myocardial infarction should improve survival by permitting successful management both of ventricular fibrillation and of other arrhythmias which may influence short term and long term prognosis.

PMID 6404481  Br Med J (Clin Res Ed). 1983 Apr 30;286(6375):1405-8.
著者: K H Newby, T Thompson, A Stebbins, E J Topol, R M Califf, A Natale
雑誌名: Circulation. 1998 Dec 8;98(23):2567-73.
Abstract/Text BACKGROUND: Sustained ventricular tachycardia (VT) and fibrillation (VF) occur in up to 20% of patients with acute myocardial infarction (MI) and have been associated with a poor prognosis. The relationships among the type of arrhythmia (VT versus VF or both), time of VT/VF occurrence, use of thrombolytic agents, and eventual outcome are unclear.
METHODS AND RESULTS: In the GUSTO-I study, we examined variables associated with the occurrence of VT/VF and its impact on mortality. Of the 40 895 patients with ventricular arrhythmia data, 4188 (10.2%) had sustained VT, VF, or both. Older age, systemic hypertension, previous MI, Killip class, anterior infarct, and depressed ejection fraction were associated with a higher risk of sustained VT and VF (P<0.001). In-hospital and 30-day mortality rates were higher among patients with sustained VT/VF than among patients without sustained ventricular arrhythmias (P<0.001). Both early (<2 days) and late (>2 days) occurrences of sustained VT and VF were associated with a higher risk of later mortality (P<0. 001). In addition, patients with both VT and VF had worse outcomes than those with either VT or VF alone (P<0.001). Among patients who survived hospitalization, no significant difference was found in 30-day mortality between the VT/VF and no VT/VF groups. However, after 1 year, the mortality rate was significantly higher in the VT alone and VT/VF groups (P<0.0001).
CONCLUSIONS: Despite the use of thrombolytic therapy, both early and late occurrences of sustained VT or VF continue to have a negative impact on patient outcome; patients with both VT and VF had the worst outcome; and among patients who survived hospitalization, the 1-year mortality rate was significantly higher in those who experienced VT alone or VT and VF.

PMID 9843464  Circulation. 1998 Dec 8;98(23):2567-73.
著者: B H Sarter, J K Finkle, R E Gerszten, A E Buxton
雑誌名: J Am Coll Cardiol. 1996 Jul;28(1):122-9.
Abstract/Text OBJECTIVES: This study sought to determine the long-term risk of sudden cardiac death in patients with hemodynamically stable sustained ventricular tachycardia complicating coronary artery disease.
BACKGROUND: The prognosis and risk of sudden cardiac death in patients with a history of myocardial infarction and ventricular tachyarrhythmias have not been clearly defined. Prior studies are limited by a short follow-up period and by inclusion of patients with heterogeneous cardiac diseases and presenting arrhythmias.
METHODS: A retrospective cohort analysis was performed on data from 124 patients, followed up for a mean of 36 +/- 30 months, who received electrophysiologically guided therapy for hemodynamically stable ventricular tachycardia after remote myocardial infarction.
RESULTS: Seventy-eight patients were treated pharmacologically (medical group), and 46 patients underwent map-guided subendocardial resection (surgical group). Nine patients (7.3%) died suddenly, 5 (4.0%) died of noncardiac causes, 9 (7.3%) died of a perioperative complication, and 20 (23.4%) died of other cardiac causes. At 1, 2 and 3 years, sudden death occurred at cumulative rates of 2 +/- 1%, 3 +/- 2% and 7 +/- 3%, whereas total mortality was 20 +/- 4%, 28 +/- 4% and 32 +/- 5% (mean +/- SD). Sudden cardiac death (p = 0.047) and total mortality (p = 0.036) were higher in patients with multivessel disease and were similar for both treatment groups.
CONCLUSIONS: Although the overall mortality in postinfarction patients presenting with hemodynamically stable ventricular tachycardia treated with electrophysiologically guided antiarrhythmic therapy is high, the risk of sudden death in these patients appears to be low (average 2.4%/year).

PMID 8752804  J Am Coll Cardiol. 1996 Jul;28(1):122-9.
著者: A Volpi, A Cavalli, R Turato, S Barlera, E Santoro, E Negri
雑誌名: Am Heart J. 2001 Jul;142(1):87-92.
Abstract/Text BACKGROUND: There is little epidemiologic information from large multicenter databases on sustained monomorphic ventricular tachycardia occurring after the initial 48 hours of myocardial infarction.
METHODS: We reassessed its incidence and short-term prognosis in 16,842 patients with a definite myocardial infarction enrolled in the Gruppo Italiano per lo Studio della Soprovvivenza nell'Infarto Miocardico (GISSI-3) trial.
RESULTS: The incidence rate of late sustained ventricular tachycardia by 6 weeks was around 1%. Older age, a history of hypertension, diabetes, and myocardial infarction, nonadministration of lytic therapy, Killip class > I, > or = 6 leads with ST-segment elevation, higher heart rate, and bundle branch block on admission were significantly more frequent among patients with than without late sustained ventricular tachycardia. Patients with ventricular tachycardia had a more complicated course in-hospital and posthospital to 6 weeks than the reference group did. The arrhythmia was associated with a significant excess of pump failure, atrial flutter-fibrillation, asystole, atrioventricular block, ventricular fibrillation within the first 48 hours of myocardial infarction, and recurrent ischemic events. Larger left ventricular end-systolic volumes and lower ejection fractions were more frequent among ventricular tachycardia patients than in the reference group by 6 weeks. Death rates by 6 weeks were 35% for patients with ventricular tachycardia and 5% for those without the arrhythmia. Irrespective of the stratification of patients by site and type of infarct and presence/absence of bundle branch block, the occurrence of the arrhythmia was associated with reduced 6-week survival.
CONCLUSION: In a proportional hazard regression model late sustained ventricular tachycardia was retained as a strong, independent predictor of 6-week mortality after myocardial infarction (hazard ratio 6.13, 95% confidence interval 4.56-8.25).

PMID 11431662  Am Heart J. 2001 Jul;142(1):87-92.
著者: Elliott M Antman, Daniel T Anbe, Paul Wayne Armstrong, Eric R Bates, Lee A Green, Mary Hand, Judith S Hochman, Harlan M Krumholz, Frederick G Kushner, Gervasio A Lamas, Charles J Mullany, Joseph P Ornato, David L Pearle, Michael A Sloan, Sidney C Smith, Joseph S Alpert, Jeffrey L Anderson, David P Faxon, Valentin Fuster, Raymond J Gibbons, Gabriel Gregoratos, Jonathan L Halperin, Loren F Hiratzka, Sharon Ann Hunt, Alice K Jacobs, American College of Cardiology, American Heart Association Task Force on Practice Guidelines, Canadian Cardiovascular Society
雑誌名: Circulation. 2004 Aug 31;110(9):e82-292.
Abstract/Text
PMID 15339869  Circulation. 2004 Aug 31;110(9):e82-292.
著者: Jane S Saczynski, Frederick A Spencer, Joel M Gore, Jerry H Gurwitz, Jorge Yarzebski, Darleen Lessard, Robert J Goldberg
雑誌名: Arch Intern Med. 2008 Oct 27;168(19):2104-10. doi: 10.1001/archinte.168.19.2104.
Abstract/Text BACKGROUND: Given the improved survival of patients after acute myocardial infarction (AMI), more patients are at risk for cerebrovascular complications of AMI. Trends in the magnitude of stroke in the setting of AMI are not well characterized, however, and neither have contemporary trends in the hospital death rates of patients developing acute stroke been examined.
RESULTS: Of 9220 patients without a history of stroke hospitalized with confirmed AMI between 1986 and 2005 in all greater Worcester medical centers, 132 (1.4%) experienced an acute stroke during hospitalization. The proportion of patients with AMI who developed a stroke increased through the 1980s and 1990s but declined slightly thereafter. Advanced age, female sex, a previous myocardial infarction (MI), and the occurrence of atrial fibrillation during hospitalization were associated with a greater risk of stroke. Receipt of a percutaneous coronary intervention during hospitalization was associated with a lower risk of stroke. Compared with patients who did not experience a stroke, patients developing a stroke in the 1990s were approximately 3 times more likely to die during hospitalization (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.72-5.19), whereas those experiencing a stroke in the 2000s were 5 times more likely to die (OR, 5.36; 95% CI, 2.71-10.64).
CONCLUSIONS: Although the incidence rates of stroke complicating AMI have declined somewhat since 1999, there is not a corresponding decline in the odds of dying during hospitalization in those developing a stroke. Although contemporary therapies may be reducing the risk of stroke in patients with AMI, more attention should be directed to improving the short-term prognosis of these high-risk patients.

PMID 18955639  Arch Intern Med. 2008 Oct 27;168(19):2104-10. doi: 10.1・・・
著者: Patrick W Serruys, Marie-Claude Morice, A Pieter Kappetein, Antonio Colombo, David R Holmes, Michael J Mack, Elisabeth Ståhle, Ted E Feldman, Marcel van den Brand, Eric J Bass, Nic Van Dyck, Katrin Leadley, Keith D Dawkins, Friedrich W Mohr, SYNTAX Investigators
雑誌名: N Engl J Med. 2009 Mar 5;360(10):961-72. doi: 10.1056/NEJMoa0804626. Epub 2009 Feb 18.
Abstract/Text BACKGROUND: Percutaneous coronary intervention (PCI) involving drug-eluting stents is increasingly used to treat complex coronary artery disease, although coronary-artery bypass grafting (CABG) has been the treatment of choice historically. Our trial compared PCI and CABG for treating patients with previously untreated three-vessel or left main coronary artery disease (or both).
METHODS: We randomly assigned 1800 patients with three-vessel or left main coronary artery disease to undergo CABG or PCI (in a 1:1 ratio). For all these patients, the local cardiac surgeon and interventional cardiologist determined that equivalent anatomical revascularization could be achieved with either treatment. A noninferiority comparison of the two groups was performed for the primary end point--a major adverse cardiac or cerebrovascular event (i.e., death from any cause, stroke, myocardial infarction, or repeat revascularization) during the 12-month period after randomization. Patients for whom only one of the two treatment options would be beneficial, because of anatomical features or clinical conditions, were entered into a parallel, nested CABG or PCI registry.
RESULTS: Most of the preoperative characteristics were similar in the two groups. Rates of major adverse cardiac or cerebrovascular events at 12 months were significantly higher in the PCI group (17.8%, vs. 12.4% for CABG; P=0.002), in large part because of an increased rate of repeat revascularization (13.5% vs. 5.9%, P<0.001); as a result, the criterion for noninferiority was not met. At 12 months, the rates of death and myocardial infarction were similar between the two groups; stroke was significantly more likely to occur with CABG (2.2%, vs. 0.6% with PCI; P=0.003).
CONCLUSIONS: CABG remains the standard of care for patients with three-vessel or left main coronary artery disease, since the use of CABG, as compared with PCI, resulted in lower rates of the combined end point of major adverse cardiac or cerebrovascular events at 1 year. (ClinicalTrials.gov number, NCT00114972.)

2009 Massachusetts Medical Society
PMID 19228612  N Engl J Med. 2009 Mar 5;360(10):961-72. doi: 10.1056/N・・・
著者: Arie Pieter Kappetein, Stuart J Head, Marie-Claude Morice, Adrian P Banning, Patrick W Serruys, Friedrich-Wilhelm Mohr, Keith D Dawkins, Michael J Mack, SYNTAX Investigators
雑誌名: Eur J Cardiothorac Surg. 2013 May;43(5):1006-13. doi: 10.1093/ejcts/ezt017. Epub 2013 Feb 14.
Abstract/Text OBJECTIVES: This prespecified subgroup analysis examined the effect of diabetes on left main coronary disease (LM) and/or three-vessel disease (3VD) in patients treated with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in the SYNTAX trial.
METHODS: Patients (n = 1800) with LM and/or 3VD were randomized to receive either PCI with TAXUS Express paclitaxel-eluting stents or CABG. Five-year outcomes in subgroups with (n = 452) or without (n = 1348) diabetes were examined: major adverse cardiac or cerebrovascular events (MACCE), the composite safety end-point of all-cause death/stroke/myocardial infarction (MI) and individual MACCE components death, stroke, MI and repeat revascularization. Event rates were estimated with Kaplan-Meier analyses.
RESULTS: In diabetic patients, 5-year rates were significantly higher for PCI vs CABG for MACCE (PCI: 46.5% vs CABG: 29.0%; P < 0.001) and repeat revascularization (PCI: 35.3% vs CABG: 14.6%; P < 0.001). There was no difference in the composite of all-cause death/stroke/MI (PCI: 23.9% vs CABG: 19.1%; P = 0.26) or individual components all-cause death (PCI: 19.5% vs CABG: 12.9%; P = 0.065), stroke (PCI: 3.0% vs CABG: 4.7%; P = 0.34) or MI (PCI: 9.0% vs CABG: 5.4%; P = 0.20). In non-diabetic patients, rates with PCI were also higher for MACCE (PCI: 34.1% vs CABG: 26.3%; P = 0.002) and repeat revascularization (PCI: 22.8% vs CABG: 13.4%; P < 0.001), but not for the composite end-point of all-cause death/stroke/MI (PCI: 19.8% vs CABG: 15.9%; P = 0.069). There were no differences in all-cause death (PCI: 12.0% vs CABG: 10.9%; P = 0.48) or stroke (PCI: 2.2% vs CABG: 3.5%; P = 0.15), but rates of MI (PCI: 9.9% vs CABG: 3.4%; P < 0.001) were significantly increased in the PCI arm in non-diabetic patients.
CONCLUSIONS: In both diabetic and non-diabetic patients, PCI resulted in higher rates of MACCE and repeat revascularization at 5 years. Although PCI is a potential treatment option in patients with less-complex lesions, CABG should be the revascularization option of choice for patients with more-complex anatomic disease, especially with concurrent diabetes.

PMID 23413014  Eur J Cardiothorac Surg. 2013 May;43(5):1006-13. doi: 1・・・
著者: Abdul Hakeem, Nadish Garg, Sabha Bhatti, Naveen Rajpurohit, Zubair Ahmed, Barry F Uretsky
雑誌名: J Am Heart Assoc. 2013 Aug 7;2(4):e000354. doi: 10.1161/JAHA.113.000354. Epub 2013 Aug 7.
Abstract/Text BACKGROUND: Controversy persists regarding the optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD). Coronary artery bypass grafting (CABG) has been compared with percutaneous coronary intervention (PCI) using drug-eluting stents (DES) in recent randomized controlled trials (RCTs).
METHODS AND RESULTS: RCTs comparing PCI with DES versus CABG in diabetic patients with MVD who met inclusion criteria were analyzed (protocol registration No. CRD42013003693). Primary end point (major adverse cardiac events) was a composite of death, myocardial infarction, and stroke at a mean follow-up of 4 years. Analyses were performed for each outcome by using risk ratio (RR) by fixed- and random-effects models. Four RCTS with 3052 patients met inclusion criteria (1539 PCI versus 1513 CABG). Incidence of major adverse cardiac events was 22.5% for PCI and 16.8% for CABG (RR 1.34, 95% CI 1.16 to 1.54, P<0.0001). Similar results were obtained for death (14% versus 9.7%, RR 1.51, 95% CI 1.09 to 2.10, P=0.01), and MI (10.3% versus 5.9%, RR 1.44, 95% CI 0.79 to 2.6, P=0.23). Stroke risk was significantly lower with DES (2.3% versus 3.8%, RR 0.59, 95% CI 0.39 to 0.90, P=0.01) and subsequent revascularization was several-fold higher (17.4% versus 8.0%, RR 1.85, 95% CI 1.0 to 3.40, P=0.05).
CONCLUSIONS: These data demonstrate that CABG in diabetic patients with MVD at low to intermediate surgical risk (defined as EUROSCORE <5) is superior to MVD PCI with DES. CABG decreased overall death, nonfatal myocardial infarction, and repeat revascularization at the expense of an increase in stroke risk.

PMID 23926119  J Am Heart Assoc. 2013 Aug 7;2(4):e000354. doi: 10.1161・・・
著者: Sanjit S Jolly, Salim Yusuf, John Cairns, Kari Niemelä, Denis Xavier, Petr Widimsky, Andrzej Budaj, Matti Niemelä, Vicent Valentin, Basil S Lewis, Alvaro Avezum, Philippe Gabriel Steg, Sunil V Rao, Peggy Gao, Rizwan Afzal, Campbell D Joyner, Susan Chrolavicius, Shamir R Mehta, RIVAL trial group
雑誌名: Lancet. 2011 Apr 23;377(9775):1409-20. doi: 10.1016/S0140-6736(11)60404-2. Epub 2011 Apr 4.
Abstract/Text BACKGROUND: Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention.
METHODS: The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voice response system to radial or femoral artery access. The primary outcome was a composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273.
FINDINGS: Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries. 3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in 128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72-1·17; p=0·50). Of the six prespecified subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28-0·87; p=0·015) and in patients with ST-segment elevation myocardial infarction (0·60, 0·38-0·94; p=0·026). The rate of death, myocardial infarction, or stroke at 30 days was 112 (3·2%) of 3507 patients in the radial group compared with 114 (3·2%) of 3514 in the femoral group (HR 0·98, 95% CI 0·76-1·28; p=0·90). The rate of non-CABG-related major bleeding at 30 days was 24 (0·7%) of 3507 patients in the radial group compared with 33 (0·9%) of 3514 patients in the femoral group (HR 0·73, 95% CI 0·43-1·23; p=0·23). At 30 days, 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group (HR 0·40, 95% CI 0·28-0·57; p<0·0001). Pseudoaneurysm needing closure occurred in seven of 3507 patients in the radial group compared with 23 of 3514 in the femoral group (HR 0·30, 95% CI 0·13-0·71; p=0·006).
INTERPRETATION: Radial and femoral approaches are both safe and effective for PCI. However, the lower rate of local vascular complications may be a reason to use the radial approach.
FUNDING: Sanofi-Aventis, Population Health Research Institute, and Canadian Network for Trials Internationally (CANNeCTIN), an initiative of the Canadian Institutes of Health Research.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 21470671  Lancet. 2011 Apr 23;377(9775):1409-20. doi: 10.1016/S01・・・
著者: Enrico Romagnoli, Giuseppe Biondi-Zoccai, Alessandro Sciahbasi, Luigi Politi, Stefano Rigattieri, Gianluca Pendenza, Francesco Summaria, Roberto Patrizi, Ambra Borghi, Cristian Di Russo, Claudio Moretti, Pierfrancesco Agostoni, Paolo Loschiavo, Ernesto Lioy, Imad Sheiban, Giuseppe Sangiorgi
雑誌名: J Am Coll Cardiol. 2012 Dec 18;60(24):2481-9. doi: 10.1016/j.jacc.2012.06.017. Epub 2012 Aug 1.
Abstract/Text OBJECTIVES: The purpose of this study was to assess whether transradial access for ST-segment elevation acute coronary syndrome undergoing early invasive treatment is associated with better outcome compared with conventional transfemoral access.
BACKGROUND: In patients with acute coronary syndrome, bleeding is a significant predictor of worse outcome. Access site complications represent a significant source of bleeding for those patients undergoing revascularization, especially when femoral access is used.
METHODS: The RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) was a multicenter, randomized, parallel-group study. Between January 2009 and July 2011, 1,001 acute ST-segment elevation acute coronary syndrome patients undergoing primary/rescue percutaneous coronary intervention were randomized to the radial (500) or femoral (501) approach at 4 high-volume centers. The primary endpoint was the 30-day rate of net adverse clinical events (NACEs), defined as a composite of cardiac death, stroke, myocardial infarction, target lesion revascularization, and bleeding). Individual components of NACEs and length of hospital stay were secondary endpoints.
RESULTS: The primary endpoint of 30-day NACEs occurred in 68 patients (13.6%) in the radial arm and 105 patients (21.0%) in the femoral arm (p = 0.003). In particular, compared with femoral, radial access was associated with significantly lower rates of cardiac mortality (5.2% vs. 9.2%, p = 0.020), bleeding (7.8% vs. 12.2%, p = 0.026), and shorter hospital stay (5 days first to third quartile range, 4 to 7 days] vs. 6 [range, 5 to 8 days]; p = 0.03).
CONCLUSIONS: Radial access in patients with ST-segment elevation acute coronary syndrome is associated with significant clinical benefits, in terms of both lower morbidity and cardiac mortality. Thus, it should become the recommended approach in these patients, provided adequate operator and center expertise is present. (Radial Versus Femoral Investigation in ST Elevation Acute Coronary Syndrome [RIFLE-STEACS]; NCT01420614).

Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 22858390  J Am Coll Cardiol. 2012 Dec 18;60(24):2481-9. doi: 10.1・・・
著者: Wassef Karrowni, Ankur Vyas, Bria Giacomino, Marin Schweizer, Amy Blevins, Saket Girotra, Phillip A Horwitz
雑誌名: JACC Cardiovasc Interv. 2013 Aug;6(8):814-23. doi: 10.1016/j.jcin.2013.04.010.
Abstract/Text OBJECTIVES: This study sought to determine the safety and efficacy of radial access compared with femoral access for primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI).
BACKGROUND: Numerous randomized controlled trials, including several new studies, have compared outcomes of these approaches in the context of primary PCI for STEMI patients with inconclusive results.
METHODS: We performed a meta-analysis of randomized controlled trials to compare outcomes in STEMI patients undergoing radial versus femoral access for primary PCI. Primary outcomes were death and major bleeding evaluated at the longest available follow-up. Secondary outcomes included access site bleeding, stroke, and procedure time. Twelve studies (N = 5,055) were included. All trials were conducted in centers experienced with both approaches.
RESULTS: Compared with femoral approach, radial approach was associated with decreased risk of mortality (2.7% vs. 4.7%; odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.40 to 0.76; p < 0.001) and decreased risk of major bleeding (1.4% vs. 2.9%; OR: 0.51, 95% CI: 0.31 to 0.85; p = 0.01). Radial access was also associated with reduction in relative risk of access site bleeding (2.1% vs. 5.6%; OR: 0.35, 95% CI: 0.25 to 0.50; p < 0.001). Stroke risk was similar between both approaches (0.5% vs. 0.5%; OR: 1.07, 95% CI: 0.45 to 2.54; p = 0.87). The procedure time was slightly longer in the radial group than in the femoral group (mean difference: 1.52 min; 95% CI: 0.33 to 2.70, p = 0.01).
CONCLUSIONS: In STEMI patients undergoing primary PCI, the radial approach is associated with favorable outcomes and should be the preferred approach for experienced radial operators.

Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 23968700  JACC Cardiovasc Interv. 2013 Aug;6(8):814-23. doi: 10.1・・・
著者: Pieter J Vlaar, Tone Svilaas, Iwan C van der Horst, Gilles F H Diercks, Marieke L Fokkema, Bart J G L de Smet, Ad F M van den Heuvel, Rutger L Anthonio, Gillian A Jessurun, Eng-Shiong Tan, Albert J H Suurmeijer, Felix Zijlstra
雑誌名: Lancet. 2008 Jun 7;371(9628):1915-20. doi: 10.1016/S0140-6736(08)60833-8.
Abstract/Text BACKGROUND: Percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction can be complicated by spontaneous or angioplasty-induced embolisation of atherothrombotic material. Distal blockage induces microvascular obstruction and can result in less than optimum reperfusion of viable myocardium. The Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) found that thrombus aspiration resulted in improved myocardial reperfusion compared with conventional PCI, but whether this benefit improves clinical outcome is unknown. We aimed to investigate whether the early efficacy of thrombus aspiration seen in TAPAS translated into clinical benefit after 1 year.
METHODS: Patients with ST-elevation myocardial infarction enrolled at the University Medical Centre Groningen were randomly assigned in a 1:1 ratio to either thrombus aspiration or conventional treatment, before undergoing initial coronary angiography. Exclusion criteria were rescue PCI after thrombolysis and known existence of a concomitant disease with life expectancy less than 6 months. Of the 1071 patients enrolled between January, 2005, and December, 2006, vital status at or beyond 1 year after randomisation was available for 1060 (99%). The primary endpoint was cardiac death or non-fatal reinfarction after 1 year, and analysis was by intention to treat. The TAPAS trial is registered with Current Controlled Trials number ISRCTN16716833.
FINDINGS: Cardiac death at 1 year was 3.6% (19 of 535 patients) in the thrombus aspiration group and 6.7% (36 of 536) in the conventional PCI group (hazard ratio [HR] 1.93; 95% CI 1.11-3.37; p=0.020). 1-year cardiac death or non-fatal reinfarction occurred in 5.6% (30 of 535) of patients in the thrombus aspiration group and 9.9% (53 of 536) of patients in the conventional PCI group (HR 1.81; 95% CI 1.16-2.84; p=0.009).
INTERPRETATION: Compared with conventional PCI, thrombus aspiration before stenting of the infarcted artery seems to improve the 1-year clinical outcome after PCI for ST-elevation myocardial infarction.

PMID 18539223  Lancet. 2008 Jun 7;371(9628):1915-20. doi: 10.1016/S014・・・
著者: Gennaro Sardella, Massimo Mancone, Chiara Bucciarelli-Ducci, Luciano Agati, Raffaele Scardala, Iacopo Carbone, Marco Francone, Angelo Di Roma, Giulia Benedetti, Giulia Conti, Francesco Fedele
雑誌名: J Am Coll Cardiol. 2009 Jan 27;53(4):309-15. doi: 10.1016/j.jacc.2008.10.017.
Abstract/Text OBJECTIVES: The purpose of this study was to evaluate the impact on myocardial perfusion and infarct size as assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of a manual thrombectomy device, Export Medtronic (EM) (Medtronic Inc., Minneapolis, Minnesota), as adjunctive therapy in primary percutaneous coronary intervention (PPCI) in a subset of patients with anterior ST-segment elevation myocardial infarction (STEMI).
BACKGROUND: PPCI may cause thrombus dislodgment, leading to microvascular damage.
METHODS: One hundred seventy-five STEMI patients were randomly assigned to standard percutaneous coronary intervention (PCI) (n = 87) or EM-PCI (n = 88). The primary end points were the occurrence of myocardial blush grade > or =2 and the rate of 90-min ST-segment resolution >70%. The CE-MRI substudy was performed in 75 patients with anterior STEMI to assess microvascular obstruction and infarct size.
RESULTS: Myocardial blush grade > or =2 and ST-segment resolution occurred more frequently in the EM-PCI group (88% vs. 60%, p = 0.001; and 64% vs. 39%, p = 0.001). In the acute phase, microvascular obstruction extent was significantly lower in the EM-PCI group and at 3 months, infarct size was significantly reduced only in the EM-PCI group. A lower incidence of cardiac death in the EM-PCI group (4.6% vs. 0%, log-rank test p = 0.02) was observed at 9 months.
CONCLUSIONS: Thrombectomy prevents thrombus embolization and preserves microvascular integrity reducing infarct size, and it therefore represents an useful adjunctive therapy in PPCI.

PMID 19161878  J Am Coll Cardiol. 2009 Jan 27;53(4):309-15. doi: 10.10・・・
著者: Giuseppe De Luca, Dariusz Dudek, Gennaro Sardella, Paolo Marino, Bernard Chevalier, Felix Zijlstra
雑誌名: Eur Heart J. 2008 Dec;29(24):3002-10. doi: 10.1093/eurheartj/ehn389. Epub 2008 Sep 5.
Abstract/Text AIMS: The benefits of adjunctive mechanical devices to prevent distal embolization in patients with acute myocardial infarction (AMI) are still a matter of debate. Growing interests are on manual thrombectomy devices as compared with other mechanical devices. In fact, they are inexpensive and user-friendly devices, and thus represent an attractive strategy. The aim of the current study was to perform an updated meta-analysis of randomized trials conducted with adjunctive manual thrombectomy devices to prevent distal embolization in AMI.
METHODS AND RESULTS: The literature was scanned by formal searches of electronic databases [MEDLINE, CENTRAL, EMBASE, and The Cochrane Central Register of Controlled trials (http://www.mrw.interscience.wiley.com/cochrane/Cochrane_clcentral_articles_fs.html)] from January 1990 to May 2008, the scientific session abstracts (from January 1990 to May 2008) and oral presentation and/or expert slide presentations (from January 2002 to May 2008) [on transcatheter coronary therapeutics (TCT), AHA (American Heart Association), ESC (European Society of Cardiology), ACC (American College of Cardiology) and EuroPCR websites]. We examined all randomized trials on adjunctive mechanical devices to prevent distal embolization in AMI. The following keywords were used: randomized trial, myocardial infarction, reperfusion, primary angioplasty, rescue angioplasty, thrombectomy, thrombus aspiration, manual thrombectomy, Diver catheter, Pronto catheter, Export catheter, thrombus vacuum aspiration catheter. Information on study design, type of device, inclusion and exclusion criteria, number of patients, and clinical outcome was extracted by two investigators. Disagreements were resolved by consensus. A total of nine trials with 2417 patients were included [1209 patients (50.0%) in the manual thrombectomy device group and 1208 (50%) in the control group]. Adjunctive manual thrombectomy was associated with significantly improved postprocedural TIMI (thrombolysis in myocardial infarction) 3 flow (87.1 vs. 81.2%, P < 0.0001), and postprocedural MBG 3 (myocardial blush grade 3) (52.1 vs. 31.7%, P < 0.0001), less distal embolization (7.9 vs. 19.5%, P < 0.0001), and significant benefits in terms of 30-day mortality (1.7 vs. 3.1%, P = 0.04).
CONCLUSION: This meta-analysis demonstrates that, among patients with AMI treated with percutaneous coronary intervention, the use of adjunctive manual thrombectomy devices is associated with better epicardial and myocardial perfusion, less distal embolization and significant reduction in 30-day mortality. Thus, adjunctive manual thrombectomy devices, if not anatomically contraindicated, should be routinely used among STEMI (ST-segment elevation myocardial infarction) patients undergoing primary angioplasty.

PMID 18775918  Eur Heart J. 2008 Dec;29(24):3002-10. doi: 10.1093/eurh・・・
著者: Charis Costopoulos, Diana A Gorog, Carlo Di Mario, Neville Kukreja
雑誌名: Int J Cardiol. 2013 Mar 10;163(3):229-41. doi: 10.1016/j.ijcard.2011.11.014. Epub 2011 Dec 3.
Abstract/Text AIMS: Primary percutaneous coronary intervention (PPCI) has become the treatment of choice in patients with ST-elevation myocardial infarction (STEMI) over the recent years. A number of studies have demonstrated a morbidity and mortality benefit over thrombolysis, which has been attributed to better coronary perfusion in patients undergoing PPCI. However although PPCI usually achieves normal flow in the affected epicardial vessel, myocardial reperfusion is not fully restored in a significant percentage of patients. This is commonly the result of distal thrombus embolization with subsequent impairment of myocardial microcirculation. Recognition of this has led to the development of a number of devices with different mechanisms of action that aim to reduce such distal embolization and therefore improve end myocardial perfusion. Recent studies indeed demonstrate that the use of such devices offer additional clinical advantage in patients undergoing PPCI compared to the current practice. This report focuses on thrombectomy devices and reviews the evidence that advocates their routine use in PPCI patients.
METHODS AND RESULTS: We have performed a systematic review of currently available thrombectomy devices. We also performed a literature search, using the terms "thrombectomy" and "thrombus aspiration" in PubMed and EMBASE. Thrombectomy devices were divided in "manual" and "non-manual" groups. We performed a meta-analysis of the available randomized control trials that compared adjunctive thrombectomy in PPCI to standard PPCI. The use of manual thrombectomy devices is associated with significant improvements in ST-segment resolution (STR) (p<0.00001), Myocardial Blush Grade (MBG) 3 (p<0.00001), Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow (p=0.01) as well as clinical parameters (43% reduction in mortality, p=0.04) in patients undergoing PPCI.
CONCLUSION: Current evidence advocates the routine use of manual thrombectomy devices in PPCI. Non-manual (mechanical) thrombectomy may have a role in selected PPCI patients with large caliber vessels and heavy thrombus burden although their routine use is not presently supported.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
PMID 22142529  Int J Cardiol. 2013 Mar 10;163(3):229-41. doi: 10.1016/・・・
著者: Giuseppe De Luca, Eliano Pio Navarese, Harry Suryapranata
雑誌名: Int J Cardiol. 2013 Jul 1;166(3):606-12. doi: 10.1016/j.ijcard.2011.11.102. Epub 2012 Jan 28.
Abstract/Text INTRODUCTION: Even though primary angioplasty restores TIMI 3 flow in more than 90% of STEMI patients, the results in terms of myocardial perfusion are still unsatisfactory in a relatively large proportion of patients. Great interest has been focused in the last years on distal embolization as major determinant of poor reperfusion and clinical outcome after primary angioplasty. The aim of this article is to perform an updated meta-analysis of thrombectomy devices in STEMI patients undergoing primary angioplasty.
METHODS: The literature was scanned by formal searches of electronic databases (MEDLINE, Pubmed) from January 1990 to December 2010, the scientific session abstracts (from January 1990 to December 2010) and oral presentation and/or expert slide presentations (from January 2002 to December 2010) (on TCT, AHA, ESC, ACC and EuroPCR websites). No language restrictions were enforced.
RESULTS: A total of 21 randomized trials were finally included in the meta-analysis, involving 4514 patients (2270 or 50.3% randomized to thrombectomy and 2244 or 49.7% to standard angioplasty). Overall thrombectomy did not reduce 30-day mortality, with more benefits observed only with manual thrombectomy. No difference was observed in the 30-day reinfarction rate, whereas a trend in higher risk of stroke was observed with thrombectomy (p=0.06). Manual but not mechanical thrombectomy significantly improved postprocedural TIMI 3 flow, however, both devices significantly improved myocardial reperfusion as evaluated by ST-segment resolution. By meta-regression analysis a linear relationship was observed between benefits from thrombectomy in ST-segment resolution and in the presence of thrombus at baseline angiography (p=0.0016).
CONCLUSIONS: The present meta-analysis has demonstrated that, among patients with STEMI, manual thrombectomy significantly improved myocardial perfusion, with a trend in short-term mortality benefits, whereas mechanical thrombectomy, despite the benefits in myocardial perfusion, did not impact on short-term survival. However, the benefits in myocardial perfusion were significantly related to prevalence of coronary thrombus. In light of the observed higher risk of stroke, thrombectomy cannot be routinely recommended, but should be used in case of evident intracoronary thrombus. Mechanical thrombectomy devices may be considered as well to further improve reperfusion and facilitate optimal stent implantation, especially in the presence of large thrombus burden.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
PMID 22284272  Int J Cardiol. 2013 Jul 1;166(3):606-12. doi: 10.1016/j・・・
著者: Anthony A Bavry, Dharam J Kumbhani, Deepak L Bhatt
雑誌名: Eur Heart J. 2008 Dec;29(24):2989-3001. doi: 10.1093/eurheartj/ehn421. Epub 2008 Sep 23.
Abstract/Text AIMS: Adjunctive thrombectomy and embolic protection devices in acute myocardial infarction have been extensively studied, although outcomes have mainly focused on surrogate markers of reperfusion. Therefore, the effect of adjunctive devices on clinical outcomes is unknown. This study sought to determine whether the use of a thrombectomy or embolic protection device during revascularization for acute myocardial infarction reduces mortality compared with percutaneous coronary intervention (PCI) alone.
METHODS AND RESULTS: The Cochrane and Medline databases were searched for clinical trials that randomized patients with ST-elevation acute myocardial infarction to an adjuvant device prior to PCI compared with PCI alone. Devices were grouped into catheter thrombus aspiration, mechanical thrombectomy, and embolic protection. There were a total of 30 studies with 6415 patients who met our selection criteria. Over a weighted mean follow-up of 5.0 months, the incidence of mortality among all studies was 3.2% for the adjunctive device group vs. 3.7% for PCI alone (relative risk, 0.87; 95% confidence interval, 0.67-1.13). Among thrombus aspiration studies, mortality was 2.7% for the adjunctive device group vs. 4.4% for PCI alone (P = 0.018), for mechanical thrombectomy, mortality was 5.3% for the adjunctive device group vs. 2.8% for PCI alone (P = 0.050), and for embolic protection, mortality was 3.1% for the adjunctive device group vs. 3.4% for PCI alone (P = 0.69).
CONCLUSION: Catheter thrombus aspiration during acute myocardial infarction is beneficial in reducing mortality compared with PCI alone. Mechanical thrombectomy appears to increase mortality, whereas embolic protection appears to have a neutral effect.

PMID 18812323  Eur Heart J. 2008 Dec;29(24):2989-3001. doi: 10.1093/eu・・・
著者: Ole Fröbert, Bo Lagerqvist, Göran K Olivecrona, Elmir Omerovic, Thorarinn Gudnason, Michael Maeng, Mikael Aasa, Oskar Angerås, Fredrik Calais, Mikael Danielewicz, David Erlinge, Lars Hellsten, Ulf Jensen, Agneta C Johansson, Amra Kåregren, Johan Nilsson, Lotta Robertson, Lennart Sandhall, Iwar Sjögren, Ollie Ostlund, Jan Harnek, Stefan K James, TASTE Trial
雑誌名: N Engl J Med. 2013 Oct 24;369(17):1587-97. doi: 10.1056/NEJMoa1308789. Epub 2013 Aug 31.
Abstract/Text BACKGROUND: The clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality.
METHODS: We conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days.
RESULTS: No patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI.
CONCLUSIONS: Routine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.).

PMID 23991656  N Engl J Med. 2013 Oct 24;369(17):1587-97. doi: 10.1056・・・
著者: Gregg W Stone, John Webb, David A Cox, Bruce R Brodie, Mansoor Qureshi, Anna Kalynych, Mark Turco, Heinz P Schultheiss, Daniel Dulas, Barry D Rutherford, David Antoniucci, Mitchell W Krucoff, Raymond J Gibbons, Denise Jones, Alexandra J Lansky, Roxana Mehran, Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris (EMERALD) Investigators
雑誌名: JAMA. 2005 Mar 2;293(9):1063-72. doi: 10.1001/jama.293.9.1063.
Abstract/Text CONTEXT: Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI) in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of which may improve reperfusion success, reduce infarct size, and enhance event-free survival.
OBJECTIVE: To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size.
DESIGN, SETTING, AND PATIENTS: Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis.
INTERVENTIONS: Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplasty without distal protection.
MAIN OUTCOME MEASURES: Coprimary end points were ST-segment resolution (STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events.
RESULTS: Among 252 patients assigned to distal protection, aspiration was performed in 97% (242/251), all angioplasty balloon inflations were fully protected in 79% (193/245), and visible debris was retrieved from 73% (182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection (63.3% [152/240] vs 61.9% [148/239], respectively; absolute difference, 1.4% [95% confidence interval, -7.7% to 10.5%; P = .78]), and left ventricular infarct size was similar in both groups (median, 12.0% [n = 229] vs 9.5% [n = 208], respectively; P = .15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups (10.0% vs 11.0%, respectively; P = .66).
CONCLUSIONS: A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.

PMID 15741528  JAMA. 2005 Mar 2;293(9):1063-72. doi: 10.1001/jama.293.・・・
著者: Shamir R Mehta, Christopher B Granger, William E Boden, Philippe Gabriel Steg, Jean-Pierre Bassand, David P Faxon, Rizwan Afzal, Susan Chrolavicius, Sanjit S Jolly, Petr Widimsky, Alvaro Avezum, Hans-Jurgen Rupprecht, Jun Zhu, Jacques Col, Madhu K Natarajan, Craig Horsman, Keith A A Fox, Salim Yusuf, TIMACS Investigators
雑誌名: N Engl J Med. 2009 May 21;360(21):2165-75. doi: 10.1056/NEJMoa0807986.
Abstract/Text BACKGROUND: Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain.
METHODS: We randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography < or = 24 hours after randomization) or delayed intervention (coronary angiography > or = 36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. A prespecified secondary outcome was death, myocardial infarction, or refractory ischemia at 6 months.
RESULTS: Coronary angiography was performed in 97.6% of patients in the early-intervention group (median time, 14 hours) and in 95.7% of patients in the delayed-intervention group (median time, 50 hours). At 6 months, the primary outcome occurred in 9.6% of patients in the early-intervention group, as compared with 11.3% in the delayed-intervention group (hazard ratio in the early-intervention group, 0.85; 95% confidence interval [CI], 0.68 to 1.06; P=0.15). There was a relative reduction of 28% in the secondary outcome of death, myocardial infarction, or refractory ischemia in the early-intervention group (9.5%), as compared with the delayed-intervention group (12.9%) (hazard ratio, 0.72; 95% CI, 0.58 to 0.89; P=0.003). Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (hazard ratio, 0.65; 95% CI, 0.48 to 0.89) but not in the two thirds at low-to-intermediate risk (hazard ratio, 1.12; 95% CI, 0.81 to 1.56; P=0.01 for heterogeneity).
CONCLUSIONS: Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients. (ClinicalTrials.gov number, NCT00552513.)

2009 Massachusetts Medical Society
PMID 19458363  N Engl J Med. 2009 May 21;360(21):2165-75. doi: 10.1056・・・
著者: Franz-Josef Neumann, Adnan Kastrati, Gisela Pogatsa-Murray, Julinda Mehilli, Hildegard Bollwein, Hans-Peter Bestehorn, Claus Schmitt, Melchior Seyfarth, Josef Dirschinger, Albert Schömig
雑誌名: JAMA. 2003 Sep 24;290(12):1593-9. doi: 10.1001/jama.290.12.1593.
Abstract/Text CONTEXT: In unstable coronary syndromes, catheter intervention is frequently preceded by antithrombotic treatment to reduce periprocedural risk; however, evidence from clinical trials to support antithrombotic pretreatment is sparse.
OBJECTIVE: To test the hypothesis that prolonged antithrombotic pretreatment improves the outcome of catheter intervention in patients with acute unstable coronary syndromes compared with early intervention.
DESIGN, SETTING, AND PATIENTS: Randomized controlled trial conducted from February 27, 2000, to April 8, 2002, and including patients admitted to 2 German tertiary care centers with symptoms of unstable angina plus either ST-segment depression or elevation of cardiac troponin T levels.
INTERVENTIONS: Patients were randomly allocated to antithrombotic pretreatment for 3 to 5 days or to early intervention after pretreatment for less than 6 hours. In both groups, antithrombotic pretreatment consisted of intravenous unfractionated heparin (60-U/kg bolus followed by infusion adjusted to maintain partial thromboplastin time of 60 to 85 seconds), aspirin (500-mg intravenous bolus followed by 100-mg twice-daily oral dose), oral clopidogrel (600-mg loading dose followed by 75-mg twice-daily dose), and intravenous tirofiban (10- microg/kg bolus followed by continuous infusion of 0.10 microg/kg per min).
MAIN OUTCOME MEASURE: Composite 30-day incidence of large nonfatal myocardial infarction or death from any cause.
RESULTS: Of the 410 patients enrolled, 207 were allocated to receive prolonged antithrombotic pretreatment and 203 to receive early intervention. Elevated levels of cardiac troponin T were present in 274 patients (67%), while 268 (65%) had ST-segment depression. The antithrombotic pretreatment and the early intervention groups were well matched with respect to major baseline characteristics and definitive treatment (catheter revascularization: 133 [64.3%] vs 143 [70.4%], respectively; coronary artery bypass graft surgery: 16 [7.7%] vs 16 [7.9%]). The primary end point was reached in 11.6% (3 deaths, 21 infarctions) of the group receiving prolonged antithrombotic pretreatment and in 5.9% (no deaths, 12 infarctions) of the group receiving early intervention (relative risk, 1.96 [95% confidence interval, 1.01-3.82]; P =.04). This outcome was attributable to events occurring before catheterization; after catheterization, both groups incurred 11 events each (P =.92).
CONCLUSION: In patients with unstable coronary syndromes, deferral of intervention for prolonged antithrombotic pretreatment does not improve the outcome compared with immediate intervention accompanied by intense antiplatelet treatment.

PMID 14506118  JAMA. 2003 Sep 24;290(12):1593-9. doi: 10.1001/jama.290・・・
著者: Karen P Alexander, L Kristin Newby, Christopher P Cannon, Paul W Armstrong, W Brian Gibler, Michael W Rich, Frans Van de Werf, Harvey D White, W Douglas Weaver, Mary D Naylor, Joel M Gore, Harlan M Krumholz, E Magnus Ohman, American Heart Association Council on Clinical Cardiology, Society of Geriatric Cardiology
雑誌名: Circulation. 2007 May 15;115(19):2549-69. doi: 10.1161/CIRCULATIONAHA.107.182615.
Abstract/Text BACKGROUND: Age is an important determinant of outcomes for patients with acute coronary syndromes (ACS); however, community practice reveals a disproportionately lower use of cardiovascular medications and invasive treatment even among elderly patients with ACS who would stand to benefit. Reasons include limited trial data to guide the care of older adults and uncertainty about benefits and risks, particularly with newer medications or invasive treatments and in the setting of advanced age or complex health status.
METHODS AND RESULTS: This 2-part American Heart Association scientific statement summarizes evidence on patient heterogeneity, clinical presentation, and treatment of non-ST-elevation ACS in relation to age (< 65, 65 to 74, 75 to 84, and > or = 85 years). In addition, we review methodological issues that influence the acquisition and application of evidence to the elderly patients treated in community practice. A writing group combining international cardiovascular and geriatric perspectives convened to summarize available data from trials (5 combined Virtual Coordinating Center for Global Collaborative Cardiovascular Research [VIGOUR] trials) and 3 registries (Global Registry of Acute Coronary Events, National Registry of Myocardial Infarction, and the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines national quality improvement initiative [CRUSADE]) to provide a conceptual framework for future work in the care of the elderly with acute cardiac disease. Treatment for non-ST-segment-elevation ACS (Part I) and ST-segment-elevation myocardial infarction (Part II) are reviewed. In addition, ethical considerations pertaining to acute care and secondary prevention are considered (Part II). The primary goal is to identify the areas in which sufficient evidence is available to guide practice, as well as to determine areas that warrant further study. Although treatment-related benefits should rise in an elderly population with high disease risk, data to assess these benefits are limited, outcomes of importance vary, and heterogeneity among the elderly increases treatment-related risks. Although a uniform approach to care in the oldest of the old is unlikely, understanding the major contributors to benefits and risks from treatment will advance the ability to apply guideline-based care in this subset of patients.
CONCLUSIONS: Although a few recent trials have described treatment effects in older patients, others continue to exclude patients on the basis of age. Going forward, prospective trials should enroll elderly subjects proportionate to their prevalence among the treated population to define risk and benefit. Findings from age subgroup analyses should be reported in a consistent manner across trials, including absolute and relative risks for efficacy and safety. Outcomes of particular relevance to the elderly, such as quality of life, physical function, and independence, should also be considered. Creatinine clearance should be calculated for every elderly patient to enable appropriate dosing. In addition, physicians need an understanding of conditions unique to older patients (eg, frailty, cognitive impairment) that influence treatment goals and outcomes. With these efforts, treatment risks can be minimized, and benefits can be placed in the health context of the elderly patient with ACS.

PMID 17502590  Circulation. 2007 May 15;115(19):2549-69. doi: 10.1161/・・・
著者: Gilles Montalescot, Guillaume Cayla, Jean-Philippe Collet, Simon Elhadad, Farzin Beygui, Hervé Le Breton, Rémi Choussat, Florence Leclercq, Johanne Silvain, François Duclos, Mounir Aout, Jean-Luc Dubois-Randé, Olivier Barthélémy, Grégory Ducrocq, Anne Bellemain-Appaix, Laurent Payot, Philippe-Gabriel Steg, Patrick Henry, Christian Spaulding, Eric Vicaut, ABOARD Investigators
雑誌名: JAMA. 2009 Sep 2;302(9):947-54. doi: 10.1001/jama.2009.1267.
Abstract/Text CONTEXT: International guidelines recommend an early invasive strategy for patients with high-risk acute coronary syndromes without ST-segment elevation, but the optimal timing of intervention is uncertain.
OBJECTIVE: To determine whether immediate intervention on admission can result in a reduction of myocardial infarction compared with a delayed intervention.
DESIGN, SETTING, AND PATIENTS: The Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention (ABOARD) study, a randomized clinical trial that assigned, from August 2006 through September 2008 at 13 centers in France, 352 patients with acute coronary syndromes without ST-segment elevation and a Thrombolysis in Myocardial Infarction (TIMI) score of 3 or more to receive intervention either immediately or on the next working day (between 8 and 60 hours after enrollment).
MAIN OUTCOME MEASURES: The primary end point was the peak troponin value during hospitalization; the key secondary end point was the composite of death, myocardial infarction, or urgent revascularization at 1-month follow-up.
RESULTS: Time from randomization to sheath insertion was 70 minutes with immediate intervention vs 21 hours with delayed intervention. The primary end point did not differ between the 2 strategies (median [interquartile range] troponin I value, 2.1 [0.3-7.1] ng/mL vs 1.7 [0.3-7.2] ng/mL in the immediate and delayed intervention groups, respectively; P = .70). The key secondary end point was observed in 13.7% (95% confidence interval, 8.6%-18.8%) of the group assigned to receive immediate intervention and 10.2% (95% confidence interval, 5.7%-14.6%) of the group assigned to receive delayed intervention (P = .31). The other end points, as well as major bleeding, did not differ between the 2 strategies.
CONCLUSION: In patients with acute coronary syndromes without ST-segment elevation, a strategy of immediate intervention compared with a strategy of intervention deferred to the next working day (mean, 21 hours) did not result in a difference in myocardial infarction as defined by peak troponin level.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00442949.

PMID 19724041  JAMA. 2009 Sep 2;302(9):947-54. doi: 10.1001/jama.2009.・・・
著者: Alexander Hirsch, Fons Windhausen, Jan G P Tijssen, Freek W A Verheugt, Jan Hein Cornel, Robbert J de Winter, Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) investigators
雑誌名: Lancet. 2007 Mar 10;369(9564):827-35. doi: 10.1016/S0140-6736(07)60410-3.
Abstract/Text BACKGROUND: The ICTUS trial was a study that compared an early invasive with a selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS). The study reported no difference between the strategies for frequency of death, myocardial infarction, or rehospitalisation after 1 year. We did a follow-up study to assess the effects of these treatment strategies after 4 years.
METHODS: 1200 patients with nSTE-ACS and an elevated cardiac troponin were enrolled from 42 hospitals in the Netherlands. Patients were randomly assigned either to an early invasive strategy, including early routine catheterisation and revascularisation where appropriate, or to a more selective invasive strategy, where catheterisation was done if the patient had refractory angina or recurrent ischaemia. The main endpoints for the current follow-up study were death, recurrent myocardial infarction, or rehospitalisation for anginal symptoms within 3 years after randomisation, and cardiovascular mortality and all-cause mortality within 4 years. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN82153174.
FINDINGS: The in-hospital revascularisation rate was 76% in the early invasive group and 40% in the selective invasive group. After 3 years, the cumulative rate for the combined endpoint was 30.0% in the early invasive group compared with 26.0% in the selective invasive group (hazard ratio 1.21; 95% CI 0.97-1.50; p=0.09). Myocardial infarction was more frequent in the early invasive strategy group (106 [18.3%] vs 69 [12.3%]; HR 1.61; 1.19-2.18; p=0.002). Rates of death or spontaneous myocardial infarction were not different (76 [14.3%] patients in the early invasive and 63 [11.2%] patients in the selective invasive strategy [HR 1.19; 0.86-1.67; p=0.30]). No difference in all-cause mortality (7.9%vs 7.7%; p=0.62) or cardiovascular mortality (4.5%vs 5.0%; p=0.97) was seen within 4 years.
INTERPRETATION: Long-term follow-up of the ICTUS trial suggests that an early invasive strategy might not be better than a more selective invasive strategy in patients with nSTE-ACS and an elevated cardiac troponin, and implementation of either strategy might be acceptable in these patients.

PMID 17350451  Lancet. 2007 Mar 10;369(9564):827-35. doi: 10.1016/S014・・・
著者: Christoph Stettler, Simon Wandel, Sabin Allemann, Adnan Kastrati, Marie Claude Morice, Albert Schömig, Matthias E Pfisterer, Gregg W Stone, Martin B Leon, José Suarez de Lezo, Jean-Jacques Goy, Seung-Jung Park, Manel Sabaté, Maarten J Suttorp, Henning Kelbaek, Christian Spaulding, Maurizio Menichelli, Paul Vermeersch, Maurits T Dirksen, Pavel Cervinka, Anna Sonia Petronio, Alain J Nordmann, Peter Diem, Bernhard Meier, Marcel Zwahlen, Stephan Reichenbach, Sven Trelle, Stephan Windecker, Peter Jüni
雑誌名: Lancet. 2007 Sep 15;370(9591):937-48. doi: 10.1016/S0140-6736(07)61444-5.
Abstract/Text BACKGROUND: Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents.
METHODS: We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation.
FINDINGS: Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel-eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66-0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021).
INTERPRETATION: The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents.

PMID 17869634  Lancet. 2007 Sep 15;370(9591):937-48. doi: 10.1016/S014・・・
著者: R A Hill, A Boland, R Dickson, Y Dündar, A Haycox, C McLeod, R Mujica Mota, T Walley, A Bagust
雑誌名: Health Technol Assess. 2007 Nov;11(46):iii, xi-221.
Abstract/Text OBJECTIVES: To assess the effectiveness and cost-effectiveness of the use of drug-eluting coronary artery stents in percutaneous coronary intervention (PCI) in patients with coronary artery disease.
DATA SOURCES: Bibliographic databases, including MEDLINE, EMBASE and the Cochrane Library, were searched from December 2002 to August 2005. Hand-searching was also done.
REVIEW METHODS: A systematic literature review of effectiveness was conducted focusing primarily on randomised controlled trials (RCTs). Full economic evaluations that compared two or more options and considered both costs and consequences were eligible for inclusion in the economics review. A critique of manufacturer submissions to the National Institute for Health and Clinical Excellence and an economic evaluation in the form of cost-utility analysis were also carried out.
RESULTS: In the 17 RCTs of drug-eluting stents (DES) versus bare metal stents (BMS), no statistically significant differences in mortality or myocardial infarction (MI) were identified up to 3 years. Significant reductions in repeat revascularisations were determined for DES compared with BMS [for example, at 1 year: target lesion revascularisation (TLR) relative risk 0.24; 95% confidence interval (CI) 0.19 to 0.31; and target vessel revascularisation (TVR) relative risk 0.43; 95% CI 0.33 to 0.55]. This estimated benefit appears to be stable from 1 to 3 years. Binary restenosis and late luminal loss also favoured DES. In the eight RCTs of DES versus DES, no statistically significant differences in mortality or MI were detected between DES designs. In meta-analyses of TLR, TVR and composite event rate, marginal improvement in efficacy of Cypher trade mark over Taxus trade mark was observed. These results await confirmation beyond 1 year and differences in study design may have influenced reporting of outcomes. Ten full economic evaluations were included in the review and the balance of evidence indicated that DES are more cost-effective in higher risk patients. The review of submitted models confirmed the view that DES may be cost-effective only under very limited circumstances when realistic assumptions and data values were used. In the cost-utility analysis of DES versus BMS, the use of DES appears to reduce the rate of repeat revascularisations; benefit estimates used in the economic assessment are defined as 'broad' (i.e. cases involving any TLR/TVR irrespective of any other lesions/vessels undergoing revascularisation) and 'narrow' (i.e. cases involving TLR/TVR only). The incremental benefit to the patient is therefore described as the loss of quality-adjusted life-years (QALYs) avoided by not having to undergo a repeat revascularisation. Univariate sensitivity analysis and extreme values analysis indicate that the price premium, numbers of stents used in the index procedure and absolute risk reduction in repeat interventions most significantly influence the cost-effectiveness ratios. Sensitivity analyses also permit a range of values for efficacy and effectiveness to be considered for individual designs of DES. The cost-effectiveness results reveal that, all patients considered together, the calculated cost per QALY ratios are high (183,000-562,000 pounds) and outside the normal range of acceptability. Cost-effectiveness is only achieved for those non-elective patients who have undergone a previous coronary artery bypass graft and have small vessels. 'Real-world' data show that patient numbers in this latter group are very small (one in 3100 of all patients treated with PCI).
CONCLUSIONS: The conclusions of the assessment are that the use of DES would be best targeted at the subgroups of patients with the highest risks of requiring reintervention, and could be considered cost-effective in only a small percentage of such patents. This is similar to the conclusion of our previous assessment. Trials of DES compared with new generation BMS and with DES would be useful, as would further evaluation of newer BMS in combination with drug administration.

PMID 17999841  Health Technol Assess. 2007 Nov;11(46):iii, xi-221.
著者: Jack V Tu, James Bowen, Maria Chiu, Dennis T Ko, Peter C Austin, Yaohua He, Robert Hopkins, Jean-Eric Tarride, Gord Blackhouse, Charles Lazzam, Eric A Cohen, Ron Goeree
雑誌名: N Engl J Med. 2007 Oct 4;357(14):1393-402. doi: 10.1056/NEJMoa071076.
Abstract/Text BACKGROUND: The placement of drug-eluting stents decreases the frequency of repeat revascularization procedures in patients undergoing percutaneous coronary intervention (PCI) in randomized clinical trials. However, there is uncertainty about the effectiveness of drug-eluting stents, and increasing concern about their safety, in routine clinical practice.
METHODS: From the Cardiac Care Network of Ontario's population-based clinical registry of all patients undergoing PCI in Ontario, Canada, we identified a well-balanced cohort of 3751 pairs of patients, matched on the basis of propensity score, who received either bare-metal stents alone or drug-eluting stents alone during an index PCI procedure between December 1, 2003, and March 31, 2005. The primary outcomes of the study were the rates of target-vessel revascularization, myocardial infarction, and death.
RESULTS: The 2-year rate of target-vessel revascularization was significantly lower among patients who received drug-eluting stents than among those who received bare-metal stents (7.4% vs. 10.7%, P<0.001). Drug-eluting stents were associated with significant reductions in the rate of target-vessel revascularization among patients with two or three risk factors for restenosis (i.e., presence of diabetes, small vessels [<3 mm in diameter], and long lesions [> or =20 mm]) but not among lower-risk patients. The 3-year mortality rate was significantly higher in the bare-metal-stent group than in the drug-eluting-stent group (7.8% vs. 5.5%, P<0.001), whereas the 2-year rate of myocardial infarction was similar in the two groups (5.2% and 5.7%, respectively; P=0.95).
CONCLUSIONS: Drug-eluting stents are effective in reducing the need for target-vessel revascularization in patients at highest risk for restenosis, without a significantly increased rate of death or myocardial infarction.

Copyright 2007 Massachusetts Medical Society.
PMID 17914040  N Engl J Med. 2007 Oct 4;357(14):1393-402. doi: 10.1056・・・
著者: J Dawn Abbott, Matthew R Voss, Mamoo Nakamura, Howard A Cohen, Faith Selzer, Kevin E Kip, Helen A Vlachos, Robert L Wilensky, David O Williams
雑誌名: J Am Coll Cardiol. 2007 Nov 20;50(21):2029-36. doi: 10.1016/j.jacc.2007.07.071.
Abstract/Text OBJECTIVES: We investigated the effectiveness and safety of drug-eluting stents (DES) as used in routine clinical practice.
BACKGROUND: Randomized trials have shown that DES prevent target vessel revascularization in selected patients, but whether this translates into superior outcomes, compared with bare-metal stents (BMS), for the full spectrum of patients treated with DES in North America is unknown.
METHODS: Patients in the National Heart, Lung, and Blood Institute Dynamic Registry enrolled in 2004 who received at least 1 DES (n = 1,460) were compared with 1,763 patients enrolled in the recruitment period immediately preceding the approval of DES (2001 to 2002) who received at least 1 BMS.
RESULTS: Patients receiving DES more often had diabetes mellitus and less often presented with an acute myocardial infarction (MI). At 1 year, cumulative death and MI was 7.6% in DES- and 8.7% in BMS-treated patients (adjusted hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.68 to 1.15; p = 0.34). The 1-year rate of target vessel revascularization was 5.0% in DES and 9.2% in BMS patients (p < 0.001), and the risk of any repeat revascularization by percutaneous coronary intervention or coronary bypass was lower in DES patients (adjusted HR 0.38, 95% CI 0.25 to 0.60; p < 0.001). Patients with both simple and complex lesion characteristics benefited from DES with lower risk of repeat target vessel revascularization by percutaneous coronary intervention compared with BMS (any complex lesion: adjusted HR 0.57, 95% CI 0.39 to 0.83; absence of any complex lesion: adjusted HR 0.44, 95% CI 0.28 to 0.71). The 1-year incidence of stent thrombosis was 1.0% in DES patients.
CONCLUSIONS: The generalized use of DES resulted in better outcomes than BMS, with fewer clinically driven revascularization procedures and similar rates of death and MI at 1 year.

PMID 18021868  J Am Coll Cardiol. 2007 Nov 20;50(21):2029-36. doi: 10.・・・
著者: Stefan K James, Ulf Stenestrand, Johan Lindbäck, Jörg Carlsson, Fredrik Scherstén, Tage Nilsson, Lars Wallentin, Bo Lagerqvist, SCAAR Study Group
雑誌名: N Engl J Med. 2009 May 7;360(19):1933-45. doi: 10.1056/NEJMoa0809902.
Abstract/Text BACKGROUND: The long-term safety and efficacy of drug-eluting coronary stents have been questioned.
METHODS: We evaluated 47,967 patients in Sweden who received a coronary stent and were entered into the Swedish Coronary Angiography and Angioplasty Registry between 2003 and 2006 and for whom complete follow-up data were available for 1 to 5 years (mean, 2.7). In the primary analysis, we compared patients who received one drug-eluting coronary stent (10,294 patients) with those who received one bare-metal stent (18,659), after adjustment for differences in clinical characteristics of the patients and characteristics of the vessels and lesions.
RESULTS: Analyses of outcome were based on 2380 deaths and 3198 myocardial infarctions. There was no overall difference between the group that received drug-eluting stents and the group that received bare-metal stents in the combined end point of death or myocardial infarction (relative risk with drug-eluting stents, 0.96; 95% confidence interval [CI], 0.89 to 1.03) or the individual end points of death (relative risk, 0.94; 95% CI, 0.85 to 1.05) and myocardial infarction (relative risk, 0.97; 95% CI, 0.88 to 1.06), and there was no significant difference in outcome among subgroups stratified according to the indication for stent implantation. Patients who received drug-eluting stents in 2003 had a significantly higher rate of late events than patients who received bare-metal stents in the same year, but we did not observe any difference in outcome among patients treated in later years. The average rate of restenosis during the first year was 3.0 events per 100 patient-years with drug-eluting stents versus 4.7 with bare-metal stents (adjusted relative risk, 0.43; 95% CI, 0.36 to 0.52); 39 patients would need to be treated with drug-eluting stents to prevent one case of restenosis. Among high-risk patients, the adjusted risk of restenosis was 74% lower with drug-eluting stents than with bare-metal stents, and only 10 lesions would need to be treated to prevent one case of restenosis.
CONCLUSIONS: As compared with bare-metal stents, drug-eluting stents are associated with a similar long-term incidence of death or myocardial infarction and provide a clinically important decrease in the rate of restenosis among high-risk patients.

2009 Massachusetts Medical Society
PMID 19420363  N Engl J Med. 2009 May 7;360(19):1933-45. doi: 10.1056/・・・
著者: Marie-Claude Morice, Patrick W Serruys, J Eduardo Sousa, Jean Fajadet, Ernesto Ban Hayashi, Marco Perin, Antonio Colombo, G Schuler, Paul Barragan, Giulio Guagliumi, Ferenc Molnàr, Robert Falotico, RAVEL Study Group. Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary Artery Lesions
雑誌名: N Engl J Med. 2002 Jun 6;346(23):1773-80. doi: 10.1056/NEJMoa012843.
Abstract/Text BACKGROUND: The need for repeated treatment of restenosis of a treated vessel remains the main limitation of percutaneous coronary revascularization. Because sirolimus (rapamycin) inhibits the proliferation of lymphocytes and smooth-muscle cells, we compared a sirolimus-eluting stent with a standard uncoated stent in patients with angina pectoris.
METHODS: We performed a randomized, double-blind trial to compare the two types of stents for revascularization of single, primary lesions in native coronary arteries. The trial included 238 patients at 19 medical centers. The primary end point was in-stent late luminal loss (the difference between the minimal luminal diameter immediately after the procedure and the diameter at six months). Secondary end points included the percentage of in-stent stenosis of the luminal diameter and the rate of restenosis (luminal narrowing of 50 percent or more). We also analyzed a composite clinical end point consisting of death, myocardial infarction, and percutaneous or surgical revascularization at 1, 6, and 12 months.
RESULTS: At six months, the degree of neointimal proliferation, manifested as the mean (+/-SD) late luminal loss, was significantly lower in the sirolimus-stent group (-0.01+/-0.33 mm) than in the standard-stent group (0.80+/-0.53 mm, P<0.001). None of the patients in the sirolimus-stent group, as compared with 26.6 percent of those in the standard-stent group, had restenosis of 50 percent or more of the luminal diameter (P<0.001). There were no episodes of stent thrombosis. During a follow-up period of up to one year, the overall rate of major cardiac events was 5.8 percent in the sirolimus-stent group and 28.8 percent in the standard-stent group (P<0.001). The difference was due entirely to a higher rate of revascularization of the target vessel in the standard-stent group.
CONCLUSIONS: As compared with a standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis, and associated clinical events.

PMID 12050336  N Engl J Med. 2002 Jun 6;346(23):1773-80. doi: 10.1056/・・・
著者: Adnan Kastrati, Julinda Mehilli, Jürgen Pache, Christoph Kaiser, Marco Valgimigli, Henning Kelbaek, Maurizio Menichelli, Manel Sabaté, Maarten J Suttorp, Dietrich Baumgart, Melchior Seyfarth, Matthias E Pfisterer, Albert Schömig
雑誌名: N Engl J Med. 2007 Mar 8;356(10):1030-9. doi: 10.1056/NEJMoa067484. Epub 2007 Feb 12.
Abstract/Text BACKGROUND: The long-term effects of treatment with sirolimus-eluting stents, as compared with bare-metal stents, have not been established.
METHODS: We performed an analysis of individual data on 4958 patients enrolled in 14 randomized trials comparing sirolimus-eluting stents with bare-metal stents (mean follow-up interval, 12.1 to 58.9 months). The primary end point was death from any cause. Other outcomes were stent thrombosis, the composite end point of death or myocardial infarction, and the composite of death, myocardial infarction, or reintervention.
RESULTS: The overall risk of death (hazard ratio, 1.03; 95% confidence interval [CI], 0.80 to 1.30) and the combined risk of death or myocardial infarction (hazard ratio, 0.97; 95% CI, 0.81 to 1.16) were not significantly different for patients receiving sirolimus-eluting stents versus bare-metal stents. There was a significant reduction in the combined risk of death, myocardial infarction, or reintervention (hazard ratio, 0.43; 95% CI, 0.34 to 0.54) associated with the use of sirolimus-eluting stents. There was no significant difference in the overall risk of stent thrombosis with sirolimus-eluting stents versus bare-metal stents (hazard ratio, 1.09; 95% CI, 0.64 to 1.86). However, there was evidence of a slight increase in the risk of stent thrombosis associated with sirolimus-eluting stents after the first year.
CONCLUSIONS: The use of sirolimus-eluting stents does not have a significant effect on overall long-term survival and survival free of myocardial infarction, as compared with bare-metal stents. There is a sustained reduction in the need for reintervention after the use of sirolimus-eluting stents. The risk of stent thrombosis is at least as great as that seen with bare-metal stents.

Copyright 2007 Massachusetts Medical Society.
PMID 17296823  N Engl J Med. 2007 Mar 8;356(10):1030-9. doi: 10.1056/N・・・
著者: Gregg W Stone, Jeffrey W Moses, Stephen G Ellis, Joachim Schofer, Keith D Dawkins, Marie-Claude Morice, Antonio Colombo, Erick Schampaert, Eberhard Grube, Ajay J Kirtane, Donald E Cutlip, Martin Fahy, Stuart J Pocock, Roxana Mehran, Martin B Leon
雑誌名: N Engl J Med. 2007 Mar 8;356(10):998-1008. doi: 10.1056/NEJMoa067193. Epub 2007 Feb 12.
Abstract/Text BACKGROUND: The safety of drug-eluting stents has been called into question by recent reports of increased stent thrombosis, myocardial infarction, and death. Such studies have been inconclusive because of their insufficient size, the use of historical controls, a limited duration of follow-up, and a lack of access to original source data.
METHODS: We performed a pooled analysis of data from four double-blind trials in which 1748 patients were randomly assigned to receive either sirolimus-eluting stents or bare-metal stents and five double-blind trials in which 3513 patients were randomly assigned to receive either paclitaxel-eluting stents or bare-metal stents; we then analyzed the major clinical end points of the trials.
RESULTS: The 4-year rates of stent thrombosis were 1.2% in the sirolimus-stent group versus 0.6% in the bare-metal-stent group (P=0.20) and 1.3% in the paclitaxel-stent group versus 0.9% in the bare-metal-stent group (P=0.30). However, after 1 year, there were five episodes of stent thrombosis in patients with sirolimus-eluting stents versus none in patients with bare-metal stents (P=0.025) and nine episodes in patients with paclitaxel-eluting stents versus two in patients with bare-metal stents (P=0.028). The 4-year rates of target-lesion revascularization were markedly reduced in both the sirolimus-stent group and the paclitaxel-stent group, as compared with the bare-metal-stent groups. The rates of death or myocardial infarction did not differ significantly between the groups with drug-eluting stents and those with bare-metal stents.
CONCLUSIONS: Stent thrombosis after 1 year was more common with both sirolimus-eluting stents and paclitaxel-eluting stents than with bare-metal stents. Both drug-eluting stents were associated with a marked reduction in target-lesion revascularization. There were no significant differences in the cumulative rates of death or myocardial infarction at 4 years.

Copyright 2007 Massachusetts Medical Society.
PMID 17296824  N Engl J Med. 2007 Mar 8;356(10):998-1008. doi: 10.1056・・・
著者: Hyeon-Cheol Gwon, Joo-Yong Hahn, Kyung Woo Park, Young Bin Song, In-Ho Chae, Do-Sun Lim, Kyoo-Rok Han, Jin-Ho Choi, Seung-Hyuk Choi, Hyun-Jae Kang, Bon-Kwon Koo, Taehoon Ahn, Jung-Han Yoon, Myung-Ho Jeong, Taek-Jong Hong, Woo-Young Chung, Young-Jin Choi, Seung-Ho Hur, Hyuck-Moon Kwon, Dong-Woon Jeon, Byung-Ok Kim, Si-Hoon Park, Nam-Ho Lee, Hui-Kyung Jeon, Yangsoo Jang, Hyo-Soo Kim
雑誌名: Circulation. 2012 Jan 24;125(3):505-13. doi: 10.1161/CIRCULATIONAHA.111.059022. Epub 2011 Dec 16.
Abstract/Text BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents.
METHODS AND RESULTS: We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72-49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60-2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42-7.03; P=0.005) among diabetic patients.
CONCLUSIONS: Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607.

PMID 22179532  Circulation. 2012 Jan 24;125(3):505-13. doi: 10.1161/CI・・・
著者: Gregg W Stone, Paul S Teirstein, Ian T Meredith, Bruno Farah, Christophe L Dubois, Robert L Feldman, Joseph Dens, Nobuhisa Hagiwara, Dominic J Allocco, Keith D Dawkins, PLATINUM Trial Investigators
雑誌名: J Am Coll Cardiol. 2011 Apr 19;57(16):1700-8. doi: 10.1016/j.jacc.2011.02.016. Epub 2011 Apr 4.
Abstract/Text OBJECTIVES: We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI).
BACKGROUND: Randomized trials have demonstrated an excellent safety and efficacy profile for the CoCr-EES. The PtCr-EES uses the identical antiproliferative agent and polymer but with a novel platinum chromium scaffold designed for enhanced deliverability, vessel conformability, side-branch access, radiopacity, radial strength, and fracture resistance.
METHODS: A total of 1,530 patients undergoing PCI of 1 or 2 de novo native lesions were randomized at 132 worldwide sites to CoCr-EES (n = 762) or PtCr-EES (n = 768). The primary endpoint was the 12-month rate of target lesion failure (TLF), the composite of target vessel-related cardiac death, target vessel-related myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR) in the per-protocol population (patients who received ≥1 assigned study stent), powered for noninferiority.
RESULTS: The 12-month rate of TLF in the per-protocol population occurred in 2.9% versus 3.4% of patients assigned to CoCr-EES versus PtCr-EES, respectively (difference: 0.5%, 95% confidence interval: -1.3% to 2.3%, p(noninferiority) = 0.001, p(superiority) = 0.60). By intention-to-treat, there were no significant differences between CoCr-EES and PtCr-EES in the 12-month rates of TLF (3.2% vs. 3.5%, p = 0.72), cardiac death or MI (2.5% vs. 2.0%, p = 0.56), TLR (1.9% vs. 1.9%, p = 0.96), or Academic Research Consortium definite or probable stent thrombosis (0.4% vs. 0.4%, p = 1.00).
CONCLUSIONS: In this large-scale, prospective, single-blind randomized trial, a novel PtCr-EES was noninferior to the predicate CoCr-EES for TLF, with nonsignificant differences in measures of safety and efficacy through 12-month follow-up after PCI.

Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 21470815  J Am Coll Cardiol. 2011 Apr 19;57(16):1700-8. doi: 10.1・・・
著者: Clemens von Birgelen, Hanim Sen, Ming Kai Lam, Peter W Danse, Gillian A J Jessurun, Raymond W M Hautvast, Gert K van Houwelingen, Alexander R Schramm, R Melvyn Tjon Joe Gin, Johannes W Louwerenburg, Frits H A F de Man, Martin G Stoel, Marije M Löwik, Gerard C M Linssen, Salah A M Saïd, Mark B Nienhuis, Patrick M J Verhorst, Mounir W Z Basalus, Carine J M Doggen, Kenneth Tandjung
雑誌名: Lancet. 2014 Feb 1;383(9915):413-23. doi: 10.1016/S0140-6736(13)62037-1. Epub 2013 Oct 31.
Abstract/Text BACKGROUND: Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial.
METHODS: In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov, number NCT01331707.
FINDINGS: Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned study treatment (six [1%] in the zotarolimus-eluting stent group vs five [1%] in the everolimus-eluting stent group; p=0·22). 12-month follow-up results were available for 1810 patients (one patient in the zotarolimus-eluting stent group withdrew consent). The primary endpoint was met by 55 (6%) of 905 patients in the zotarolimus-eluting stent group and 47 (5%) of 905 in the everolimus-eluting stent group. The zotarolimus-eluting stent was non-inferior to the everolimus-eluting stent (absolute risk difference 0·88%, 95% CI -1·24% to 3·01%; upper limit of one-sided 95% CI 2·69%; non-inferiority p=0·006). We noted no significant between-group differences in individual components of the primary endpoint. Definite stent thrombosis occurred in three (0·3%) patients in the zotarolimus-eluting stent group and six (0·7%) patients in the everolimus-eluting stent group (p=0·34). Longitudinal stent deformation was seen only in the everolimus-eluting stent group (nine [1·0%] of 905 vs 0 of 906, p=0·002; nine of 1591 [0·6%] everolimus-eluting stents implanted became deformed), but was not associated with any adverse events.
INTERPRETATION: Both stents were similarly efficacious and safe, and provided excellent clinical outcomes, especially in view of the large number of patients who presented with acute myocardial infarctions.
FUNDING: Boston Scientific, Medtronic.

Copyright © 2014 Elsevier Ltd. All rights reserved.
PMID 24183564  Lancet. 2014 Feb 1;383(9915):413-23. doi: 10.1016/S0140・・・
著者: Duk-Woo Park, Myeong-Ki Hong, Il-Woo Suh, Eui-Seock Hwang, Se-Whan Lee, Young-Hoon Jeong, Young-Hak Kim, Cheol Whan Lee, Jae-Joong Kim, Seong-Wook Park, Seung-Jung Park
雑誌名: Am J Cardiol. 2007 Mar 15;99(6):760-5. doi: 10.1016/j.amjcard.2006.10.028. Epub 2007 Jan 22.
Abstract/Text The correlates of angiographic and clinical outcomes after drug-eluting stent (DES) implantation for aorto-ostial lesions remain unknown. This study evaluated long-term results of DES implantation for aorto-ostial lesions and determined risk factors for restenosis and adverse cardiac events. In total, 184 consecutive patients who underwent DES implantation for aorto-ostial lesions were investigated (DES group) compared with 172 consecutive patients treated with bare metal stents before the introduction of DESs (pre-DES group). Major adverse cardiac events (MACEs) were defined as death, Q-wave myocardial infarction, and need for target lesion revascularization. The DES group had significantly higher risk clinical and procedural profiles than the pre-DES group. Procedural success rates were 99.5% in the DES group and 100% in the pre-DES group (p = 1.0). The DES group had a significantly lower incidence of in-segment restenosis (10.5% vs 26.0%, p = 0.001) and target lesion revascularization (4.3% vs 11.6%, p = 0.011). Cumulative MACE rates at 1 year were 6.5% in the DES group and 13.4% in the pre-DES group (p = 0.03). By multivariate analysis, treatment of bypass graft, treatment of in-stent restenosis, and reference vessel diameter were predictors of restenosis, and only reference vessel diameter (hazard ratio 0.20, 95% confidence interval 0.05 to 0.75, p = 0.017) inversely correlated with 1-year MACEs after DES implantation. In conclusion, DES implantation for aorto-ostial lesions is associated with a significant decrease in restenosis and MACEs compared with the pre-DES phase. Treatment of bypass graft and in-stent restenosis and reference vessel size were identified as predictors of restenosis and/or long-term MACEs after DES implantation.

PMID 17350360  Am J Cardiol. 2007 Mar 15;99(6):760-5. doi: 10.1016/j.a・・・
著者: Rasha Al-Lamee, Alfonso Ielasi, Azeem Latib, Cosmo Godino, Marco Mussardo, Francesco Arioli, Filippo Figin, Daniela Piraino, Mauro Carlino, Matteo Montorfano, Alaide Chieffo, Antonio Colombo
雑誌名: Am J Cardiol. 2011 Oct 15;108(8):1055-60. doi: 10.1016/j.amjcard.2011.06.004. Epub 2011 Jul 24.
Abstract/Text Percutaneous coronary intervention (PCI) to aorto-ostial (AO) lesions is technically demanding and associated with high revascularization rates. The aim of this study was to assess outcomes after bare metal stent (BMS) compared to drug-eluting stent (DES) implantation after PCI to AO lesions. A retrospective cohort analysis was conducted of all consecutive patients who underwent PCI to AO lesions at 2 centers. Angiographic and clinical outcomes in 230 patients with DES from September 2000 to December 2009 were compared to a historical control group of 116 patients with BMS. Comparison of the baseline demographics showed more diabetics (32% vs 16%, p = 0.001), lower ejection fractions (52.3 ± 9.7% vs 55.0 ± 11.5%, p = 0.022), longer stents (17.55 ± 7.76 vs 14.37 ± 5.60 mm, p <0.001), and smaller final stent minimum luminal diameters (3.43 ± 0.53 vs 3.66 ± 0.63 mm, p = 0.001) in the DES versus BMS group. Angiographic follow-up (DES 68%, BMS 66%) showed lower restenosis rates with DES (20% vs 47%, p <0.001). At clinical follow-up, target lesion revascularization rates were lowest with DES (12% vs 27%, p = 0.001). Cox regression analysis with propensity score adjustment for baseline differences suggested that DES were associated with a reduction in target lesion revascularization (hazard ratios 0.28, 95% confidence interval 0.15 to 0.52, p <0.001) and major adverse cardiac events (hazard ratio 0.50, 95% confidence interval 0.32 to 0.79, p = 0.003). There was a nonsignificantly higher incidence of Academic Research Consortium definite and probable stent thrombosis with DES (n = 9 [4%] vs n = 1 [1%], p = 0.131). In conclusion, despite differences in baseline characteristics favoring the BMS group, PCI with DES in AO lesions was associated with improved outcomes, with lower restenosis, revascularization, and major adverse cardiac event rates.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21791332  Am J Cardiol. 2011 Oct 15;108(8):1055-60. doi: 10.1016/・・・
著者: Ioannis Iakovou, Lei Ge, Iassen Michev, Giuseppe M Sangiorgi, Matteo Montorfano, Flavio Airoldi, Alaide Chieffo, Goran Stankovic, Giancarlo Vitrella, Mauro Carlino, Nicola Corvaja, Carlo Briguori, Antonio Colombo
雑誌名: J Am Coll Cardiol. 2004 Sep 1;44(5):967-71. doi: 10.1016/j.jacc.2004.05.058.
Abstract/Text OBJECTIVES: This observational study evaluated the clinical and angiographic outcomes of patients with aorto-ostial coronary artery disease treated with sirolimus-eluting stents (SESs) or with bare metal stents (BMSs).
BACKGROUND: The safety and effectiveness of SESs for the treatment of aorto-ostial lesions have not been demonstrated.
METHODS: We identified 82 consecutive patients who underwent percutaneous coronary interventions in 82 aorto-ostial lesions using the SES (32 patients) or BMS (50 patients) and compared the two groups of patients. The incidence of major adverse cardiac events (MACE), including death or Q-wave myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR), were recorded in-hospital and at a 10-month follow-up.
RESULTS: All stents were implanted successfully. There were no statistically significant differences regarding major in-hospital complications between the two groups. At 10-month follow-up, two (6.3%) patients in the SES group and 14 (28%) patients in the BMS group underwent TLR (p = 0.01); MACE were less frequent in the SES group compared to the BMS group (19% vs. 44%, p = 0.02). Angiographic follow-up showed lower binary restenosis rates (11% vs. 51%, p = 0.001) and smaller late loss (0.21 +/- 0.31 mm vs. 2.06 +/- 1.37 mm, p < 0.0001) in the SES group.
CONCLUSIONS: The main finding of our study is that, compared to the BMS, implantation of the SES in aorto-ostial lesions appears safe and effective, with no increase in major in-hospital complications and a significant improvement in restenosis and late event rates at 10-month follow-up.

PMID 15337205  J Am Coll Cardiol. 2004 Sep 1;44(5):967-71. doi: 10.101・・・
著者: Seung-Whan Lee, Sung-Hwan Kim, Seon-Ok Kim, Seungbong Han, Young-Hak Kim, Duk-Woo Park, Soo-Jin Kang, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
雑誌名: Catheter Cardiovasc Interv. 2012 Aug 1;80(2):206-12. doi: 10.1002/ccd.23369. Epub 2012 Jan 10.
Abstract/Text BACKGROUND: To date, drug-eluting stent (DES) implantation has not been compared with coronary artery bypass grafting (CABG) for ostial left main coronary artery (LMCA) lesions.
METHODS: Of the 263 patients in the MAIN-COMPARE registry with ostial LMCA stenosis, 123 were treated with percutaneous coronary intervention (PCI) with DES and 140 with CABG. We compared their 5-year overall survival, composite outcomes of death, Q-wave myocardial infarction (MI) or stroke, and target vessel revascularization (TVR) rates.
RESULTS: Unadjusted analysis showed no significant differences between CABG and DES in overall survival rates (95% confidence interval (CI) for hazard ratio (HR): 0.44 to 1.77, P = 0.71), composite outcomes (death, Q-wave MI, or stroke)-free survival rates (95% CI for HR: 0.41-1.63, P = 0.56), and TVR-free survival rates (95% CI for HR: 0.79-5.03, P = 0.14). Multivariate adjusted Cox regression analysis also showed no significant between-group differences in TVR (95% CI for HR: 0.52-3.79, P = 0.49), death (95% CI for HR: 0.79-2.82, P = 0.22) and the composite of death, Q-wave MI, or stroke (95% CI for HR: 0.65-2.57, P = 0.46). These results were sustained after propensity score adjustment and propensity score matching analysis.
CONCLUSIONS: DES implantation for ostial LMCA lesions showed similar 5-year outcomes of death, major adverse events, and TVR compared with CABG. Although meticulous adjustments decreased baseline difference between the two treatments, the absence of statistical significance could be attributable to the size of the study sample and hidden bias.

Copyright © 2012 Wiley Periodicals, Inc.
PMID 22234884  Catheter Cardiovasc Interv. 2012 Aug 1;80(2):206-12. do・・・
著者: Ioannis Iakovou, Lei Ge, Antonio Colombo
雑誌名: J Am Coll Cardiol. 2005 Oct 18;46(8):1446-55. doi: 10.1016/j.jacc.2005.05.080. Epub 2005 Sep 28.
Abstract/Text Treatment of coronary bifurcation lesions represents a challenging area in interventional cardiology. The introduction of drug-eluting stents (DES) reduced restenosis in the main branch (MB). However, restenosis at the ostium of the side branch (SB) remains a problem. Although stenting the MB with provisional SB stenting seems to be the prevailing approach, in the era of DES various two-stent techniques emerged (crush) or were re-introduced (V or simultaneous kissing stents, crush, T, culottes, Y, skirt) to allow stenting in the SB when needed. This review describes in detail various techniques used for implantation of two stents by intention to treat.

PMID 16226167  J Am Coll Cardiol. 2005 Oct 18;46(8):1446-55. doi: 10.1・・・
著者: Michael Maeng, Niels R Holm, Andrejs Erglis, Indulis Kumsars, Matti Niemelä, Kari Kervinen, Jan S Jensen, Anders Galløe, Terje K Steigen, Rune Wiseth, Inga Narbute, Pål Gunnes, Jan Mannsverk, Oliver Meyerdierks, Svein Rotevatn, Kjell Nikus, Saila Vikman, Jan Ravkilde, Stefan James, Jens Aarøe, Antti Ylitalo, Steffen Helqvist, Iwar Sjögren, Per Thayssen, Kari Virtanen, Mikko Puhakka, Juhani Airaksinen, Evald H Christiansen, Jens F Lassen, Leif Thuesen, Nordic-Baltic Percutaneous Coronary Intervention Study Group
雑誌名: J Am Coll Cardiol. 2013 Jul 2;62(1):30-4. doi: 10.1016/j.jacc.2013.04.015. Epub 2013 May 1.
Abstract/Text OBJECTIVES: This study sought to report the 5-year follow-up results of the Nordic Bifurcation Study.
BACKGROUND: Randomized clinical trials with short-term follow-up have indicated that coronary bifurcation lesions may be optimally treated using the optional side branch stenting strategy.
METHODS: A total of 413 patients with a coronary bifurcation lesion were randomly assigned to a simple stenting strategy of main vessel (MV) and optional stenting of side branch (SB) or to a complex stenting strategy, namely, stenting of both MV and SB.
RESULTS: Five-year clinical follow-up data were available for 404 (98%) patients. The combined safety and efficacy endpoint of cardiac death, non-procedure-related myocardial infarction, and target vessel revascularization were seen in 15.8% in the optional SB stenting group as compared to 21.8% in the MV and SB stenting group (p = 0.15). All-cause death was seen in 5.9% versus 10.4% (p = 0.16) and non-procedure-related myocardial infarction in 4% versus 7.9% (p = 0.09) in the optional SB stenting group versus the MV and SB stenting group, respectively. The rates of target vessel revascularization were 13.4% versus 18.3% (p = 0.14) and the rates of definite stent thrombosis were 3% versus 1.5% (p = 0.31) in the optional SB stenting group versus the MV and SB stenting group, respectively.
CONCLUSIONS: At 5-year follow-up in the Nordic Bifurcation Study, the clinical outcomes after simple optional side branch stenting remained at least equal to the more complex strategy of planned stenting of both the main vessel and the side branch.

Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 23644088  J Am Coll Cardiol. 2013 Jul 2;62(1):30-4. doi: 10.1016/・・・
著者: Miroslaw Ferenc, Michael Gick, Rolf-Peter Kienzle, Hans-Peter Bestehorn, Klaus-Dieter Werner, Thomas Comberg, Min Zhao, Heinz Joachim Buettner, Franz-Josef Neumann
雑誌名: Am Heart J. 2010 Mar;159(3):454-61. doi: 10.1016/j.ahj.2009.11.032.
Abstract/Text BACKGROUND: The purpose of this study was to assess the long-term risks and benefits of drug-eluting stents (DESs) compared with bare-metal stents (BMSs) for treatment of coronary bifurcation lesions.
METHODS: Our registry comprised 1,038 patients treated for coronary bifurcation lesion according to the provisional T-stenting strategy who were followed up for 3 years.
RESULTS: Target lesion revascularization rates were 24.3% for BMSs (n = 337), 15.6% for sirolimus-eluting stents (SESs, n = 422), and 17.3% for paclitaxel-eluting stents (PESs, n = 279) (P = .003 BMSs vs DESs, P = .54 SESs vs PESs). The respective incidences were 11.4%, 9.5%, and 14.8% (P = .65, P = .13) for death and myocardial infarction and 9.9%, 6.5%, and 10.6% (P = .72, P = .19) for death. Propensity score adjusted hazard ratios (95% CI) for DESs versus BMSs were 0.49 (0.35-0.68, P < .001) for target lesion revascularization, 0.94 (0.64-1.40, P = .078) for death and myocardial infarction, and 0.85 (0.55-1.32, P = .47) for death. We did not find any significant differences between SESs and PESs, except for an increased risk of death after PESs compared with SESs (but not BMSs) in the subgroup receiving a side-branch stent (adjusted hazard ratio 2.45, 95% CI 1.05-5.73, P = .035).
CONCLUSIONS: Compared with BMSs, both PESs and SESs substantially reduced the long-term need for repeated revascularization but did not increase the risk of death and myocardial infarction.

PMID 20211309  Am Heart J. 2010 Mar;159(3):454-61. doi: 10.1016/j.ahj.・・・
著者: David Hildick-Smith, Adam J de Belder, Nina Cooter, Nicholas P Curzen, Tim C Clayton, Keith G Oldroyd, Lorraine Bennett, Steve Holmberg, James M Cotton, Peter E Glennon, Martyn R Thomas, Philip A Maccarthy, Andreas Baumbach, Niall T Mulvihill, Robert A Henderson, Simon R Redwood, Ian R Starkey, Rodney H Stables
雑誌名: Circulation. 2010 Mar 16;121(10):1235-43. doi: 10.1161/CIRCULATIONAHA.109.888297. Epub 2010 Mar 1.
Abstract/Text BACKGROUND: The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques.
METHODS AND RESULTS: Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64+/-10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations (>50% narrowing in both vessels). In the simple group (n=250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n=250), 89% of culotte (n=75) and 72% of crush (n=169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P=0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P=0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P=0.002), respectively. Procedure duration and x-ray dose favored the simple approach.
CONCLUSIONS: When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00351260.

PMID 20194880  Circulation. 2010 Mar 16;121(10):1235-43. doi: 10.1161/・・・
著者: Miles W Behan, Niels R Holm, Nicholas P Curzen, Andrejs Erglis, Rodney H Stables, Adam J de Belder, Matti Niemelä, Nina Cooter, Derek P Chew, Terje K Steigen, Keith G Oldroyd, Jan S Jensen, Jens Flensted Lassen, Leif Thuesen, David Hildick-Smith
雑誌名: Circ Cardiovasc Interv. 2011 Feb 1;4(1):57-64. doi: 10.1161/CIRCINTERVENTIONS.110.958512. Epub 2011 Jan 4.
Abstract/Text BACKGROUND: Controversy persists regarding the correct strategy for bifurcation lesions. Therefore, we combined the patient-level data from 2 large trials with similar methodology: the NORDIC Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study (BBC ONE).
METHODS AND RESULTS: Both randomized trials compared simple (provisional T-stenting) versus complex techniques, using drug-eluting stents. In the simple group (n=457), 129 patients had final kissing balloon dilatation in addition to main vessel stenting, and 16 had T-stenting. In the complex group (n=456), 272 underwent crush, 118 culotte, and 59 T-stenting techniques. A composite end point at 9 months of all-cause death, myocardial infarction, and target vessel revascularization occurred in 10.1% of the simple versus 17.3% of the complex group (hazard ratio 1.84 [95% confidence interval 1.28 to 2.66], P=0.001). Procedure duration, contrast, and x-ray dose favored the simple approach. Subgroup analysis revealed similar composite end point results for true bifurcations (n=657, simple 9.2% versus complex 17.3%; hazard ratio 1.90 [95% confidence interval 1.22 to 2.94], P=0.004), wide-angled bifurcations >60 to 70° (n=217, simple 9.6% versus complex 15.7%; hazard ratio 1.67 [ 95% confidence interval 0.78 to 3.62], P=0.186), large (≥2.75 mm) diameter side branches (n=281, simple 10.4% versus complex 20.7%; hazard ratio 2.42 [ 95% confidence interval 1.22 to 4.80], P=0.011), longer length (>5 mm) ostial side branch lesions (n=464, simple 12.1% versus complex 19.1%; hazard ratio 1.71 [95% confidence interval 1.05 to 2.77], P=0.029), or equivalent sized vessels (side branch <0.25 mm smaller than main vessel) (n=108, simple 12.0% versus complex 15.5%; hazard ratio 1.35 [95% confidence interval 0.48 to 3.70], P=0.57).
CONCLUSIONS: For bifurcation lesions, a provisional single-stent approach is superior to systematic dual stenting techniques in terms of safety and efficacy. A complex approach does not appear to be beneficial in more anatomically complicated lesions.

PMID 21205942  Circ Cardiovasc Interv. 2011 Feb 1;4(1):57-64. doi: 10.・・・
著者: Shao-Liang Chen, Teguh Santoso, Jun-Jie Zhang, Fei Ye, Ya-Wei Xu, Qiang Fu, Jing Kan, Chitprapai Paiboon, Yong Zhou, Shi-Qing Ding, Tak W Kwan
雑誌名: J Am Coll Cardiol. 2011 Feb 22;57(8):914-20. doi: 10.1016/j.jacc.2010.10.023.
Abstract/Text OBJECTIVES: The present study aimed to investigate the difference in major adverse cardiac events (MACE) at 12 months in patients with coronary bifurcation lesions after double kissing double crush (DK crush) or provisional stenting (PS) techniques.
BACKGROUND: Provisional side branch (SB) stenting is preferable to DK crush because it has been associated with fewer complications. It is unknown which strategy would provide the best results.
METHODS: From April 2007 to June 2009, 370 unselected patients with coronary bifurcation lesions from 7 Asian centers were randomly assigned to either the DK or the PS group. Additional SB stenting in PS was required if final results were suboptimal. The primary end point was the occurrence of MACE at 12 months, including cardiac death, myocardial infarction, or target vessel revascularization (TVR). Secondary end point was the angiographic restenosis at 8 months.
RESULTS: There were 3 procedural occlusions of SB in the PS group. At 8 months, angiographic restenosis rates in the main vessel and SB were significantly different between the DK (3.8% and 4.9%) and the PS groups (9.7% and 22.2%, p = 0.036 and p < 0.001, respectively). Additional SB stenting in the PS group was required in 28.6% of lesions. TVR was 6.5% in the DK group, occurring significantly less often than in the PS group (14.6%, p = 0.017). There were nonsignificant differences in MACE and definite stent thrombosis between the DK (10.3% and 2.2%) and PS groups (17.3%, and 0.5%, p = 0.070 and p = 0.372, respectively).
CONCLUSIONS: DK crush was associated with a significant reduction of TLR and TVR in this unselected patient population. However, there was no significant difference in MACE between DK and the PS groups. (Randomized Study on DK Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions; ChicTR-TRC-00000015).

Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 21329837  J Am Coll Cardiol. 2011 Feb 22;57(8):914-20. doi: 10.10・・・
著者: Abid R Assali, Hana Vaknin-Assa, Eli Lev, Igal Teplitsky, Danny Dvir, David Brosh, Tamir Bental, Alexander Battler, Ran Kornowski
雑誌名: Catheter Cardiovasc Interv. 2012 Mar 1;79(4):615-22. doi: 10.1002/ccd.23180. Epub 2011 Dec 7.
Abstract/Text OBJECTIVES: To explore the long-term results following implantation of drug-eluting stents (DES) in bifurcation lesions according to contemporary "real world" practice.
BACKGROUND: Limited information is available on the long-term outcomes of patients with bifurcation lesions who are treated using DES. A systematic approach for bifurcation lesion management was applied, using either a "provisional" single stent technique or a dedicated two stents strategy according to the side-branch diameter and severity of its ostial stenosis.
METHODS: Four hundred one consecutive patients underwent bifurcation percutaneous coronary intervention (PCI) using DES and were included in our prospective registry. All adverse events were recorded up to 2 years and distinguished according to the planned PCI strategy (e.g., one versus two stents technique).
RESULTS: A planned two stents strategy was used in 141 patients (35% of patients). In 260 patients (65%), the planned treatment involved stenting of the main branch only with "provisional" stenting of the side-branch according to procedural course. Thus, 24 patients (9.2%) needed additional stenting at the side-branch to complete the PCI. Cumulative major adverse cardiac event rate at 1 and 2 years was similar for both groups (11.4% vs. 14.8% at 1 year and 19.4% vs. 25.7% at 2 years for the single vs. two stents groups, accordingly, P = NS for both). Likewise, there was no difference in mortality, cardiac mortality, myocardial infarction, need for target lesions or target vessel revascularization, or definite stent thrombosis rate between the two groups at 6, 12, and 2 years follow-up. The rate of angiographically confirmed (i.e., definite) stent thrombosis did not differ between the two groups during follow-up.
CONCLUSIONS: Our study revealed favorable long-term clinical results following DES implantation using a systematic, rather simplified approach towards bifurcation stenting and using either a single or double stenting technique.

Copyright © 2011 Wiley Periodicals, Inc.
PMID 22162218  Catheter Cardiovasc Interv. 2012 Mar 1;79(4):615-22. do・・・
著者: Bimmer E Claessen, George D Dangas, Cosmo Godino, Seung-Whan Lee, Kotaro Obunai, Mauro Carlino, Jung-Won Suh, Martin B Leon, Carlo Di Mario, Seung-Jung Park, Gregg W Stone, Jeffrey W Moses, Antonio Colombo, Roxana Mehran, Multinational Cto Registry
雑誌名: Am J Cardiol. 2011 Oct 1;108(7):924-31. doi: 10.1016/j.amjcard.2011.05.021. Epub 2011 Aug 3.
Abstract/Text There is a paucity of data on long-term outcomes after percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) in the high-risk group of patients with diabetes mellitus (DM). The aim of this study was to evaluate long-term clinical outcomes after PCI of CTOs in patients with and without DM. A total of 1,742 patients with known DM status underwent PCI of CTOs at 3 tertiary care centers in the United States, South Korea, and Italy from 1998 to 2007. Five-year clinical outcomes were evaluated in patients with successful versus failed CTO PCI and the use of drug-eluting stents (DES) versus bare-metal stents (BMS) stratified according to DM status. A total of 395 patients (23%) had DM (42% of whom had insulin-dependent DM). Procedural success was similar in patients with versus without DM (69.6% vs 67.9%, p = 0.53). After successful CTO PCI, stents were implanted in 96.4% of patients with DM (BMS in 23.8%, DES in 76.2%) and in 94.0% of patients without DM (BMS in 38.6%, DES in 61.4%). Median follow-up was 3.0 years. In patients with DM, successful CTO PCI was associated with reduced long-term mortality (10.4% vs 13.0%, p <0.05) and a reduced need for coronary artery bypass grafting (2.4% vs 15.7%, p <0.01). The use of DES was associated with a reduction in target vessel revascularization in patients with DM (14.8% vs 54.1%, p <0.01) and in those without DM (17.6% vs 26.5%, p <0.01). Multivariate analysis identified insulin-dependent DM as an independent predictor of mortality in the DM cohort. In conclusion, successful CTO PCI in patients with DM was associated with a reduction in mortality and the need for coronary artery bypass grafting. Compared to non-insulin-dependent DM, patients with insulin-dependent DM had an increased risk for long-term mortality. The use of DES rather than BMS was associated with a reduction in target vessel revascularization in patients with and without DM.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21820095  Am J Cardiol. 2011 Oct 1;108(7):924-31. doi: 10.1016/j.・・・
著者: Roxana Mehran, Bimmer E Claessen, Cosmo Godino, George D Dangas, Kotaro Obunai, Sunil Kanwal, Mauro Carlino, José P S Henriques, Carlo Di Mario, Young-Hak Kim, Seung-Jung Park, Gregg W Stone, Martin B Leon, Jeffrey W Moses, Antonio Colombo, Multinational Chronic Total Occlusion Registry
雑誌名: JACC Cardiovasc Interv. 2011 Sep;4(9):952-61. doi: 10.1016/j.jcin.2011.03.021.
Abstract/Text OBJECTIVES: The aim of this study was to evaluate long-term clinical outcomes after percutaneous coronary intervention (PCI) for chronic total occlusions (CTO).
BACKGROUND: Despite technical advancements, there is a paucity of data on long-term outcomes after PCI of CTO.
METHODS: We evaluated long-term clinical outcomes in 1,791 patients who underwent PCI of 1,852 CTO at 3 tertiary care centers in the United States, South Korea, and Italy between 1998 and 2007. Median follow-up was 2.9 years (interquartile range: 1.5 to 4.6 years).
RESULTS: Procedural success was obtained in 1,226 (68%) patients. Stents were implanted in 1,160 patients (95%); 396 patients (34%) received bare-metal stents (BMS), and 764 patients (66%) received drug-eluting stents (DES). After multivariable analysis, successful CTO PCI was an independent predictor of a lower cardiac mortality (hazard ratio [HR]: 0.40, 95% confidence interval [CI]: 0.21 to 0.75, p < 0.01) and reduced need for coronary artery bypass graft surgery (HR: 0.21, 95% CI: 0.13 to 0.40, p < 0.01); it also correlated with a strong trend toward lower all-cause mortality (HR: 0.63, 95% CI: 0.40 to 1.00, p = 0.05) at 5-year follow-up. Among patients who underwent stent implantation, treatment with DES rather than BMS resulted in less target vessel revascularization at long-term follow-up (17.2% vs. 31.1%, p < 0.01); definite/probable stent thrombosis rates were similar (DES 1.7%, BMS 2.3%, p = 0.58). Within the DES subgroup, patients treated with paclitaxel-eluting stents and sirolimus-eluting stents had similar clinical outcomes.
CONCLUSIONS: Successful CTO PCI is associated with reduced long-term cardiac mortality and need for coronary artery bypass graft surgery. Treatment of CTO with DES rather than BMS is associated with a significant reduction in target vessel revascularization with similar rates of stent thrombosis. Paclitaxel-eluting stents and sirolimus-eluting stents had similar long-term safety and efficacy outcomes.

Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 21939934  JACC Cardiovasc Interv. 2011 Sep;4(9):952-61. doi: 10.1・・・
著者: Daniel A Jones, Roshan Weerackody, Krishnaraj Rathod, Jonathan Behar, Sean Gallagher, Charles J Knight, Akhil Kapur, Ajay K Jain, Martin T Rothman, Craig A Thompson, Anthony Mathur, Andrew Wragg, Elliot J Smith
雑誌名: JACC Cardiovasc Interv. 2012 Apr;5(4):380-8. doi: 10.1016/j.jcin.2012.01.012.
Abstract/Text OBJECTIVES: This study investigated the impact of procedural success on mortality following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in a large cohort of patients in the drug-eluting stent era.
BACKGROUND: Despite advances in expertise and technologies, many patients with CTO are not offered PCI.
METHODS: A total of 6,996 patients underwent elective PCI for stable angina at a single center (2003 to 2010), 836 (11.9%) for CTO. All-cause mortality was obtained to 5 years (median: 3.8 years; interquartile range: 2.0 to 5.4 years) and stratified according to successful chronic total occlusion (sCTO) or unsuccessful chronic total occlusion (uCTO) recanalization. Major adverse cardiac events (MACE) included myocardial infarction (MI), urgent revascularization, stroke, or death.
RESULTS: A total of 582 (69.6%) procedures were successful. Stents were implanted in 97.0% of successful procedures (mean: 2.3 ± 0.1 stents per patient, 73% drug-eluting). Prior revascularization was more frequent among uCTO patients: coronary artery bypass grafting (CABG) (16.5% vs. 7.4%; p < 0.0001), PCI (36.0% vs. 21.2%; p < 0.0001). Baseline characteristics were otherwise similar. Intraprocedural complications, including coronary dissection, were more frequent in unsuccessful cases (20.5% vs. 4.9%; p < 0.0001), but did not affect in-hospital MACE (3% vs. 2.1%; p = NS). All-cause mortality was 17.2% for uCTO and 4.5% for sCTO at 5 years (p < 0.0001). The need for CABG was reduced following sCTO (3.1% vs. 22.1%; p < 0.0001). Multivariate analysis demonstrated that procedural success was independently predictive of mortality (hazard ratio [HR]: 0.32 [95% confidence interval (CI): 0.18 to 0.58]), which persisted when incorporating a propensity score (HR: 0.28 [95% CI: 0.15 to 0.52]).
CONCLUSIONS: Successful CTO PCI is associated with improved survival out to 5 years. Adoption of techniques and technologies to improve procedural success may have an impact on prognosis.

Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 22516393  JACC Cardiovasc Interv. 2012 Apr;5(4):380-8. doi: 10.10・・・
著者: Dominique Joyal, Jonathan Afilalo, Stéphane Rinfret
雑誌名: Am Heart J. 2010 Jul;160(1):179-87. doi: 10.1016/j.ahj.2010.04.015.
Abstract/Text BACKGROUND: Chronic total occlusion (CTO) recanalizations remain extremely challenging procedures. With improvements in technology and techniques, success rates for recanalization of CTO continue to improve. However, the clinical benefits of this practice remain unclear. The aim of the study was to determine the effectiveness of CTO recanalization on clinical outcomes.
METHODS: We performed a systematic review and meta-analysis of published studies comparing CTO recanalization to medical management. Data were extracted in duplicate and analyzed by a random effects model.
RESULTS: We did not identify any randomized controlled trials or observational studies comparing CTO recanalization to a planned medical management. We did identify 13 observational studies comparing outcomes after successful vs failed CTO recanalization attempt. These studies encompassed 7,288 patients observed over a weighted average follow-up of 6 years. There were 721 (14.3%) deaths of 5,056 patients after successful CTO recanalization compared to 390 deaths (17.5%) of 2,232 patients after failed CTO recanalization (odds ratio [OR] 0.56, 95% CI 0.43-0.72). Successful recanalization was associated with a significant reduction in subsequent coronary artery bypass graft surgery (CABG) (OR 0.22, 95% CI 0.17-0.27) but not in myocardial infarction (OR 0.74, 95% CI 0.44-1.25) or major adverse cardiac events (OR 0.81, 95% CI 0.55-1.21). In the 6 studies that reported angina status, successful recanalization was associated with a significant reduction in residual/recurrent angina (OR 0.45, 95% CI 0.30-0.67).
CONCLUSIONS: In highly selected patients considered for CTO recanalization, successful attempts appear to be associated with an improvement in mortality and with a reduction for the need for CABG as compared to failed recanalization. However, given the observational nature of the reviewed evidence, randomized clinical trials are needed to confirm these findings.

Copyright (c) 2010 Mosby, Inc. All rights reserved.
PMID 20598990  Am Heart J. 2010 Jul;160(1):179-87. doi: 10.1016/j.ahj.・・・
著者: J Aaron Grantham, Philip G Jones, Louis Cannon, John A Spertus
雑誌名: Circ Cardiovasc Qual Outcomes. 2010 May;3(3):284-90. doi: 10.1161/CIRCOUTCOMES.108.825760. Epub 2010 Apr 13.
Abstract/Text BACKGROUND: Data on the health status benefits of percutaneous coronary intervention for coronary chronic total occlusions (CTOs), a principal indication for the procedure, are lacking.
METHODS AND RESULTS: In the FlowCardia Approach to CTO Recanalization (FACTOR) trial, patients (n=125) completed the Seattle Angina Questionnaire (SAQ) at baseline and 1 month after percutaneous coronary intervenion. One-month health status outcomes were compared by multivariable analysis, adjusting for group differences between those whose CTO was successfully and unsuccessfully recanalized. These changes were also analyzed according to baseline symptoms. Procedural success was 55% (n=64) and independently associated with angina relief (difference between those with successful and unsuccessful percutaneous coronary intervention [Delta] in SAQ angina frequency=9.5 points; 95% confidence interval, 1.6 to 17.5; P=0.019), improved physical function (Delta in SAQ physical limitation=13.1 points; 95% confidence interval, 5.1 to 21.1; P=0.001), and enhanced quality of life (Delta in SAQ quality of life [QoL]=20.3 points; 95% confidence interval, 11.9 to 28.6; P<0.001). The benefit of successful percutaneous coronary intervention was greatest in symptomatic patients as compared with asymptomatic patients although statistically significantly so only for QoL (DeltaSAQ angina frequency domain=10.3 versus 4.3 points, P=0.51, Deltaphysical limitation =15.9 versus 6.3 points, P=0.25; DeltaQoL=27.3 versus 8.5 points, P=0.047).
CONCLUSIONS: Successful CTO recanalization is associated with significant early improvements in patient symptoms, function, and QoL but only among symptomatic patients. Percutaneous treatment of a CTO offers the potential to provide significant health status benefits in symptomatic patients.

PMID 20388873  Circ Cardiovasc Qual Outcomes. 2010 May;3(3):284-90. do・・・
著者: Somjot S Brar, Albert Yuh-Jer Shen, Michael B Jorgensen, Adam Kotlewski, Vicken J Aharonian, Natasha Desai, Michael Ree, Ahmed Ijaz Shah, Raoul J Burchette
雑誌名: JAMA. 2008 Sep 3;300(9):1038-46. doi: 10.1001/jama.300.9.1038.
Abstract/Text CONTEXT: Sodium bicarbonate has been suggested as a possible strategy for prevention of contrast medium-induced nephropathy, a common cause of renal failure associated with prolonged hospitalization, increased health care costs, and substantial morbidity and mortality.
OBJECTIVE: To determine if sodium bicarbonate is superior to sodium chloride for preventing contrast medium-induced nephropathy in patients with moderate to severe chronic kidney dysfunction who are undergoing coronary angiography.
DESIGN, SETTING, AND PATIENTS: Randomized, controlled, single-blind study conducted between January 2, 2006, and January 31, 2007, and enrolling 353 patients with stable renal disease who were undergoing coronary angiography at a single US center. Included patients were 18 years or older and had an estimated glomerular filtration rate of 60 mL/min per 1.73 m(2) or less and 1 or more of diabetes mellitus, history of congestive heart failure, hypertension, or age older than 75 years.
INTERVENTIONS: Patients were randomized to receive either sodium chloride (n = 178) or sodium bicarbonate (n = 175) administered at the same rate (3 mL/kg for 1 hour before coronary angiography, decreased to 1.5 mL/kg per hour during the procedure and for 4 hours after the completion of the procedure).
MAIN OUTCOME MEASURE: The primary end point was a 25% or greater decrease in the estimated glomerular filtration rate on days 1 through 4 after contrast exposure.
RESULTS: Median patient age was 71 (interquartile range, 65-76) years, and 45% had diabetes mellitus. The groups were well matched for baseline characteristics. The primary end point was met in 13.3% of the sodium bicarbonate group and 14.6% of the sodium chloride group (relative risk, 0.94; 95% confidence interval, 0.55-1.60; P = .82). In patients randomized to receive sodium bicarbonate vs sodium chloride, the rates of death, dialysis, myocardial infarction, and cerebrovascular events did not differ significantly at 30 days (1.7% vs 1.7%, 0.6% vs 1.1%, 0.6% vs 0%, and 0% vs 2.2%, respectively) or at 30 days to 6 months (0.6% vs 2.3%, 0.6% vs 1.1%, 0.6% vs 2.3%, and 0.6% vs 1.7%, respectively) (P > .10 for all).
CONCLUSION: The results of this study do not suggest that hydration with sodium bicarbonate is superior to hydration with sodium chloride for the prevention of contrast medium-induced nephropathy in patients with moderate to severe chronic kidney disease who are undergoing coronary angiography.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00312117.

PMID 18768415  JAMA. 2008 Sep 3;300(9):1038-46. doi: 10.1001/jama.300.・・・
著者: Gregory J Merten, W Patrick Burgess, Lee V Gray, Jeremiah H Holleman, Timothy S Roush, Glen J Kowalchuk, Robert M Bersin, Arl Van Moore, Charles A Simonton, Robert A Rittase, H James Norton, Thomas P Kennedy
雑誌名: JAMA. 2004 May 19;291(19):2328-34. doi: 10.1001/jama.291.19.2328.
Abstract/Text CONTEXT: Contrast-induced nephropathy remains a common complication of radiographic procedures. Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure. Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury. However, no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy.
OBJECTIVE: To examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast.
DESIGN, SETTING, AND PATIENTS: A prospective, single-center, randomized trial conducted from September 16, 2002, to June 17, 2003, of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL (> or =97.2 micromol/L) who were randomized to receive a 154-mEq/L infusion of either sodium chloride (n = 59) or sodium bicarbonate (n = 60) before and after iopamidol administration (370 mg iodine/mL). Serum creatinine levels were measured at baseline and 1 and 2 days after contrast.
INTERVENTIONS: Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate, as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure.
MAIN OUTCOME MEASURE: Contrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine within 2 days of contrast.
RESULTS: There were no significant group differences in age, sex, incidence of diabetes mellitus, ethnicity, or contrast volume. Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment (mean [SD], 1.71 [0.42] mg/dL [151.2 [37.1] micromol/L] for sodium chloride and 1.89 [0.69] mg/dL [167.1 [61.0] micromol/L] for sodium bicarbonate; P =.09). The primary end point of contrast-induced nephropathy occurred in 8 patients (13.6%) infused with sodium chloride but in only 1 (1.7%) of those receiving sodium bicarbonate (mean difference, 11.9%; 95% confidence interval [CI], 2.6%-21.2%; P =.02). A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study resulted in 3 cases of contrast-induced nephropathy (1.6%; 95% CI, 0%-3.4%).
CONCLUSION: Hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure.

PMID 15150204  JAMA. 2004 May 19;291(19):2328-34. doi: 10.1001/jama.29・・・
著者: Mauro Maioli, Anna Toso, Mario Leoncini, Carlo Micheletti, Francesco Bellandi
雑誌名: Circ Cardiovasc Interv. 2011 Oct 1;4(5):456-62. doi: 10.1161/CIRCINTERVENTIONS.111.961391. Epub 2011 Oct 4.
Abstract/Text BACKGROUND: Intravascular volume expansion represents a beneficial measure against contrast-induced acute kidney injury (CI-AKI) in patients undergoing elective angiographic procedures. However, the efficacy of this preventive strategy has not yet been established for patients with ST-elevation-myocardial infarction (STEMI), who are at higher risk of this complication after primary percutaneous coronary intervention (PCI). In this randomized study we investigated the possible beneficial role of periprocedural intravenous volume expansion and we compared the efficacy of 2 different hydration strategies in patients with STEMI undergoing primary PCI.
METHODS AND RESULTS: We randomly assigned 450 STEMI patients to receive (1) preprocedure and postprocedure hydration of sodium bicarbonate (early hydration group), (2) postprocedure hydration of isotonic saline (late hydration group), or (3) no hydration (control group). The primary end point was the development of CI-AKI, defined as an increase in serum creatinine of ≥25% or 0.5 mg/dL over the baseline value within 3 days after administration of the contrast medium. Moreover, we evaluated a possible relationship between the occurrence of CI-AKI and total hydration volume administered. There were no significant differences in baseline clinical, biochemical, and procedural characteristics in the 3 groups. Overall, CI-AKI occurred in 93 patients (20.6%): the incidence was significantly lower in the early hydration group (12%) with respect to both the late hydration group (22.7%) and the control group (27.3%) (P for trend=0.001). In hydrated patients (early and late hydration groups), lower infused volumes were associated with a significant increase in CI-AKI incidence, and the optimal cutoff point of hydration volume that best discriminates patients at higher risk was ≤960 mL.
CONCLUSIONS: Adequate intravenous volume expansion may prevent CI-AKI in patients undergoing primary PCI. A regimen of preprocedure and postprocedure hydration therapy with sodium bicarbonate appears to be more efficacious than postprocedure hydration only with isotonic saline.

PMID 21972403  Circ Cardiovasc Interv. 2011 Oct 1;4(5):456-62. doi: 10・・・
著者: Carlo Briguori, Gabriella Visconti, Amelia Focaccio, Flavio Airoldi, Marco Valgimigli, Giuseppe Massimo Sangiorgi, Bruno Golia, Bruno Ricciardelli, Gerolama Condorelli, REMEDIAL II Investigators
雑誌名: Circulation. 2011 Sep 13;124(11):1260-9. doi: 10.1161/CIRCULATIONAHA.111.030759. Epub 2011 Aug 15.
Abstract/Text BACKGROUND: The RenalGuard System, which creates high urine output and fluid balancing, may be beneficial in preventing contrast-induced acute kidney injury.
METHODS AND RESULTS: The Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II) trial is a randomized, multicenter, investigator-driven trial addressing the prevention of contrast-induced acute kidney injury in high-risk patients. Patients with an estimated glomerular filtration rate ≤30 mL · min(-1) · 1.73 m(-2) and/or a risk score ≥11 were randomly assigned to sodium bicarbonate solution and N-acetylcysteine (control group) or hydration with saline and N-acetylcysteine controlled by the RenalGuard System and furosemide (RenalGuard group). The primary end point was an increase of ≥0.3 mg/dL in the serum creatinine concentration at 48 hours after the procedure. The secondary end points included serum cystatin C kinetics and rate of in-hospital dialysis. Contrast-induced acute kidney injury occurred in 16 of 146 patients in the RenalGuard group (11%) and in 30 of 146 patients in the control group (20.5%; odds ratio, 0.47; 95% confidence interval, 0.24 to 0.92). There were 142 patients (48.5%) with an estimated glomerular filtration rate ≤30 mL · min(-1) · 1.73 and 149 patients (51.5%) with only a risk score ≥11. Subgroup analysis according to inclusion criteria showed a similarly lower risk of adverse events (estimated glomerular filtration rate ≤30 mL · min(-1) · 1.73 m(-2): odds ratio, 0.44; risk score ≥11: odds ratio, 0.45; P for interaction=0.97). Changes in cystatin C at 24 hours (0.02±0.32 versus -0.08±0.26; P=0.002) and 48 hours (0.12±0.42 versus 0.03±0.31; P=0.001) and the rate of in-hospital dialysis (4.1% versus 0.7%; P=0.056) were higher in the control group.
CONCLUSION: RenalGuard therapy is superior to sodium bicarbonate and N-acetylcysteine in preventing contrast-induced acute kidney injury in high-risk patients.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrial.gov. Unique identifier: NCT01098032.

PMID 21844075  Circulation. 2011 Sep 13;124(11):1260-9. doi: 10.1161/C・・・
著者: Giancarlo Marenzi, Cristina Ferrari, Ivana Marana, Emilio Assanelli, Monica De Metrio, Giovanni Teruzzi, Fabrizio Veglia, Franco Fabbiocchi, Piero Montorsi, Antonio L Bartorelli
雑誌名: JACC Cardiovasc Interv. 2012 Jan;5(1):90-7. doi: 10.1016/j.jcin.2011.08.017.
Abstract/Text OBJECTIVES: This study investigated the effect of furosemide-forced diuresis and intravenous saline infusion matched with urine output, using a novel dedicated device designed for contrast-induced nephropathy (CIN) prevention.
BACKGROUND: CIN is a frequent cause of acute kidney injury associated with increased morbidity and mortality.
METHODS: A total of 170 consecutive patients with chronic kidney disease (CKD) undergoing coronary procedures were randomized to either furosemide with matched hydration (FMH group, n = 87) or to standard intravenous isotonic saline hydration (control group; n = 83). The FMH group received an initial 250-ml intravenous bolus of normal saline over 30 min followed by an intravenous bolus (0.5 mg/kg) of furosemide. Hydration infusion rate was automatically adjusted to precisely replace the patient's urine output. When a urine output rate >300 ml/h was obtained, patients underwent the coronary procedure. Matched fluid replacement was maintained during the procedure and for 4 h post-treatment. The definition of CIN was a ≥25% or ≥0.5 mg/dl rise in serum creatinine over baseline.
RESULTS: In the FMH group, no device- or therapy-related complications were observed. Four (4.6%) patients in the FMH group developed CIN versus 15 (18%) controls (p = 0.005). A lower incidence of cumulative in-hospital clinical complications was also observed in FMH-treated patients than in controls (8% vs. 18%; p = 0.052).
CONCLUSIONS: In patients with CKD undergoing coronary procedures, furosemide-induced high urine output with matched hydration significantly reduces the risk of CIN and may be associated with improved in-hospital outcome. (Induced Diuresis With Matched Hydration Compared to Standard Hydration for Contrast Induced Nephropathy Prevention [MYTHOS]; NCT00702728).

Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 22230154  JACC Cardiovasc Interv. 2012 Jan;5(1):90-7. doi: 10.101・・・
著者: Giancarlo Marenzi, Emilio Assanelli, Jeness Campodonico, Gianfranco Lauri, Ivana Marana, Monica De Metrio, Marco Moltrasio, Marco Grazi, Mara Rubino, Fabrizio Veglia, Franco Fabbiocchi, Antonio L Bartorelli
雑誌名: Ann Intern Med. 2009 Feb 3;150(3):170-7.
Abstract/Text BACKGROUND: Contrast-induced nephropathy (CIN) frequently occurs in patients with acute ST-segment elevation myocardial infarction (STEMI) who are undergoing primary percutaneous coronary intervention, and CIN is associated with a more complicated clinical course and increased mortality.
OBJECTIVE: To investigate the association between absolute and weight- and creatinine-adjusted contrast volume, CIN incidence, and clinical outcome in the era of mechanical reperfusion of STEMI.
DESIGN: Prospective, observational study.
SETTING: A university cardiology center in Milan, Italy.
PATIENTS: 561 consecutive patients with STEMI who were undergoing primary percutaneous coronary intervention.
MEASUREMENTS: For each patient, the maximum contrast dose was calculated, according to the formula (5 x body weight [kg])/serum creatinine, and the contrast ratio, defined as the ratio between the contrast volume administered and the maximum dose calculated, was assessed. An increase in serum creatinine of more than 25% from baseline was defined as CIN.
RESULTS: 115 (20.5%) patients developed CIN. In-hospital mortality was higher among patients with CIN than those without CIN (21.4% vs. 0.9%; P < 0.001). The maximum contrast dose was exceeded in 130 (23%) patients. Patients who received more than the maximum contrast dose (contrast ratio >1) had a more complicated in-hospital clinical course and higher mortality rate (13% vs. 2.8%; P < 0.001) than did patients with a contrast ratio less than 1. Development of CIN was associated with both contrast volume and contrast ratio.
LIMITATION: The association between contrast volume and outcomes was observed in a single center and could be due to comorbid conditions, disease severity, or an unknown factor.
CONCLUSION: During primary percutaneous coronary intervention for STEMI, higher contrast volume is associated with higher rates of CIN and mortality; however, further study is needed to determine whether limiting contrast volume would improve patient outcome.
FUNDING: Centro Cardiologico Monzino, Institute of Cardiology, University of Milan.

PMID 19189906  Ann Intern Med. 2009 Feb 3;150(3):170-7.
著者: Warren K Laskey, Charles Jenkins, Faith Selzer, Oscar C Marroquin, Robert L Wilensky, Ruchira Glaser, Howard A Cohen, David R Holmes, NHLBI Dynamic Registry Investigators
雑誌名: J Am Coll Cardiol. 2007 Aug 14;50(7):584-90. doi: 10.1016/j.jacc.2007.03.058. Epub 2007 Jul 30.
Abstract/Text OBJECTIVES: This study sought to validate a pharmacokinetically derived measure of the risk of an early increase in serum creatinine after percutaneous coronary intervention (PCI).
BACKGROUND: The ratio of the volume of contrast media to the creatinine clearance (V/CrCl) has been shown to correlate with the area under the curve of contrast media concentration over time.
METHODS: We calculated V/CrCl in 3,179 consecutive patients undergoing PCI. An increase in serum creatinine of >0.5 mg/dl by 24 to 48 h was considered abnormal. Receiver-operator characteristic methods were used to identify the optimal sensitivity and specificity for the observed range of V/CrCl. The predictive value of V/CrCl for the risk of an early increase in creatinine was assessed using multivariable logistic regression.
RESULTS: The overall incidence of an abnormal, early increase in creatinine was 1.5%. The mean and median values of V/CrCl for patients with (mean 5.2 +/- 4.4, median 4.3, interquartile range 2.7 to 6.0) and without (mean 3.0 +/- 2.0, median 2.5, interquartile range 1.7 to 3.8) an early creatinine increase were each significantly (p < 0.001) different between groups. Furthermore, there was a significant association between V/CrCl and an early increase in creatinine (overall and trend, p < 0.001). The receiver-operator characteristic curve analysis indicated that a V/CrCl ratio of 3.7 was a fair discriminator for the early creatinine increase (C-statistic 0.69). After adjusting for other known predictors of post-PCI creatinine increase, V/CrCl > or =3.7 remained significantly associated with an early abnormal increase in serum creatinine (odds ratio 3.84; 95% confidence interval 2.0 to 7.3, p < 0.001).
CONCLUSIONS: A V/CrCl ratio >3.7 was a significant and independent predictor of an early abnormal increase in serum creatinine after PCI in this unselected patient population.

PMID 17692741  J Am Coll Cardiol. 2007 Aug 14;50(7):584-90. doi: 10.10・・・
著者: Peter Aspelin, Pierre Aubry, Sven-Göran Fransson, Ruth Strasser, Roland Willenbrock, Knut Joachim Berg, Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media Study Investigators
雑誌名: N Engl J Med. 2003 Feb 6;348(6):491-9. doi: 10.1056/NEJMoa021833.
Abstract/Text BACKGROUND: The use of iodinated contrast medium can result in nephropathy. Whether iso-osmolar contrast medium is less nephrotoxic than low-osmolar contrast medium in high-risk patients is uncertain.
METHODS: We conducted a randomized, double-blind, prospective, multicenter study comparing the nephrotoxic effects of an iso-osmolar, dimeric, nonionic contrast medium, iodixanol, with those of a low-osmolar, nonionic, monomeric contrast medium, iohexol. The study involved 129 patients with diabetes with serum creatinine concentrations of 1.5 to 3.5 mg per deciliter who underwent coronary or aortofemoral angiography. The primary end point was the peak increase from base line in the creatinine concentration during the three days after angiography. Other end points were an increase in the creatinine concentration of 0.5 mg per deciliter or more, an increase of 1.0 mg per deciliter or more, and a change in the creatinine concentration from day 0 to day 7.
RESULTS: The creatinine concentration increased significantly less in patients who received iodixanol. From day 0 to day 3, the mean peak increase in creatinine was 0.13 mg per deciliter in the iodixanol group and 0.55 mg per deciliter in the iohexol group (P=0.001; the increase with iodixanol minus the increase with iohexol, -0.42 mg per deciliter [95 percent confidence interval, -0.73 to -0.22]). Two of the 64 patients in the iodixanol group (3 percent) had an increase in the creatinine concentration of 0.5 mg per deciliter or more, as compared with 17 of the 65 patients in the iohexol group (26 percent) (P=0.002; odds ratio for such an increase in the iodixanol group, 0.09 [95 percent confidence interval, 0.02 to 0.41]). No patient receiving iodixanol had an increase of 1.0 mg per deciliter or more, but 10 patients in the iohexol group (15 percent) did. The mean change in the creatinine concentration from day 0 to day 7 was 0.07 mg per deciliter in the iodixanol group and 0.24 mg per deciliter in the iohexol group (P=0.003; value in the iodixanol group minus the value in the iohexol group, -0.17 mg per deciliter [95 percent confidence interval, -0.34 to -0.07]).
CONCLUSIONS: Nephropathy induced by contrast medium may be less likely to develop in high-risk patients when iodixanol is used rather than a low-osmolar, nonionic contrast medium.

Copyright 2003 Massachusetts Medical Society
PMID 12571256  N Engl J Med. 2003 Feb 6;348(6):491-9. doi: 10.1056/NEJ・・・
著者: Sang-Ho Jo, Tae-Jin Youn, Bon-Kwon Koo, Jin-Shik Park, Hyun-Jae Kang, Young-Seok Cho, Woo-Young Chung, Gwon-Wook Joo, In-Ho Chae, Dong-Ju Choi, Byung-Hee Oh, Myoung-Mook Lee, Young-Bae Park, Hyo-Soo Kim
雑誌名: J Am Coll Cardiol. 2006 Sep 5;48(5):924-30. doi: 10.1016/j.jacc.2006.06.047. Epub 2006 Aug 17.
Abstract/Text OBJECTIVES: This study sought to compare the nephrotoxicity of iodixanol and ioxaglate in patients with renal impairment undergoing coronary angiography.
BACKGROUND: Iodixanol, a nonionic, dimeric, iso-osmolar contrast medium (IOCM), may be less nephrotoxic than low-osmolar contrast media (LOCM) in high-risk patients.
METHODS: In a prospective, randomized trial in 300 adults with creatinine clearance (CrCl) < or =60 ml/min, patients received either iodixanol or ioxaglate and underwent coronary angiography with or without percutaneous coronary intervention. The primary end point was the incidence of contrast-induced nephropathy (CIN) (an increase in serum creatinine [SCr] > or =25% or > or =0.5 mg/dl [> or =44.2 mumol/l]). The incidence of CIN in patients with severe renal impairment at baseline (CrCl <30 ml/min) or diabetes and in those receiving large doses (> or =140 ml) of contrast medium was also determined.
RESULTS: The incidence of CIN was significantly lower with iodixanol (7.9%) than with ioxaglate (17.0%; p = 0.021), corresponding to an odds ratio (OR) of CIN of 0.415 (95% confidence interval [CI] 0.194 to 0.889) for iodixanol. The incidence of CIN was also significantly lower with iodixanol in patients with severe renal impairment (p = 0.023) or concomitant diabetes (p = 0.041), or in patients given > or =140 ml of contrast media (p = 0.038). Multivariate analysis identified use of ioxaglate (OR 2.65, 95% CI 1.11 to 6.33, p = 0.028), baseline SCr, mg/dl (OR 2.0, 95% CI 1.04 to 3.85, p = 0.038), and left ventricular ejection fraction, % (OR 0.97, 95% CI 0.94 to 0.99, p = 0.019) as independent risk factors for CIN.
CONCLUSIONS: The IOCM iodixanol was significantly less nephrotoxic than ioxaglate, an ionic, dimeric LOCM. (The RECOVER Trial; http://clinicaltrials.gov; NCT00247325).

PMID 16949481  J Am Coll Cardiol. 2006 Sep 5;48(5):924-30. doi: 10.101・・・
著者: Richard J Solomon, Madhu K Natarajan, Serge Doucet, Samin K Sharma, Cezar S Staniloae, Richard E Katholi, Joseph L Gelormini, Marino Labinaz, Abel E Moreyra, Investigators of the CARE Study
雑誌名: Circulation. 2007 Jun 26;115(25):3189-96. doi: 10.1161/CIRCULATIONAHA.106.671644. Epub 2007 Jun 11.
Abstract/Text BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients.
METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01).
CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.

PMID 17562951  Circulation. 2007 Jun 26;115(25):3189-96. doi: 10.1161/・・・
著者: David Meyre, Philippe Froguel, Fritz F Horber, John G Kral
雑誌名: PLoS One. 2014;9(3):e93324. doi: 10.1371/journal.pone.0093324. Epub 2014 Mar 31.
Abstract/Text
PMID 24686325  PLoS One. 2014;9(3):e93324. doi: 10.1371/journal.pone.0・・・
著者: Mario Leoncini, Anna Toso, Mauro Maioli, Francesco Tropeano, Simona Villani, Francesco Bellandi
雑誌名: J Am Coll Cardiol. 2014 Jan 7-14;63(1):71-9. doi: 10.1016/j.jacc.2013.04.105. Epub 2013 Sep 26.
Abstract/Text OBJECTIVES: This study sought to determine if in addition to standard preventive measures on-admission, high-dose rosuvastatin exerts a protective effect against contrast-induced acute kidney injury (CI-AKI).
BACKGROUND: Patients with acute coronary syndrome (ACS) are at high risk for CI-AKI, and the role of statin pre-treatment in preventing renal damage remains uncertain.
METHODS: Consecutive statin-naïve non-ST elevation ACS patients scheduled to undergo early invasive strategy were randomly assigned to receive rosuvastatin (40 mg on admission, followed by 20 mg/day; statin group n = 252) or no statin treatment (control group n = 252). CI-AKI was defined as an increase in creatinine concentration of ≥0.5 mg/dl or ≥25% above baseline within 72 h after contrast administration.
RESULTS: The incidence of CI-AKI was significantly lower in the statin group than in controls (6.7% vs. 15.1%; adjusted odds ratio: 0.38; 95% confidence interval [CI]: 0.20 to 0.71; p = 0.003). The benefits against CI-AKI were consistent, even applying different CI-AKI definition criteria and in all the pre-specified risk categories. The 30-day incidence of adverse cardiovascular and renal events (death, dialysis, myocardial infarction, stroke, or persistent renal damage) was significantly lower in the statin group (3.6% vs. 7.9%, respectively; p = 0.036). Moreover, statin treatment given on admission was associated with a lower rate of death or nonfatal myocardial infarction at 6 month follow-up (3.6% vs. 7.2%, respectively; p = 0.07).
CONCLUSIONS: High-dose rosuvastatin given on admission to statin-naïve patients with ACS who are scheduled for an early invasive procedure can prevent CI-AKI and improve short-term clinical outcome. (Statin Contrast Induced Nephropathy Prevention [PRATO-ACS]; NCT01185938).

Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 24076283  J Am Coll Cardiol. 2014 Jan 7-14;63(1):71-9. doi: 10.10・・・
著者: Giancarlo Marenzi, Ivana Marana, Gianfranco Lauri, Emilio Assanelli, Marco Grazi, Jeness Campodonico, Daniela Trabattoni, Franco Fabbiocchi, Piero Montorsi, Antonio L Bartorelli
雑誌名: N Engl J Med. 2003 Oct 2;349(14):1333-40. doi: 10.1056/NEJMoa023204.
Abstract/Text BACKGROUND: Nephropathy induced by exposure to radiocontrast agents, a possible complication of percutaneous coronary interventions, is associated with significant in-hospital and long-term morbidity and mortality. Patients with preexisting renal failure are at particularly high risk. We investigated the role of hemofiltration, as compared with isotonic-saline hydration, in preventing contrast-agent-induced nephropathy in patients with renal failure.
METHODS: We studied 114 consecutive patients with chronic renal failure (serum creatinine concentration, >2 mg per deciliter [176.8 micromol per liter]) who were undergoing coronary interventions. We randomly assigned them to either hemofiltration in an intensive care unit (ICU) (58 patients, with a mean [+/-SD] serum creatinine concentration of 3.0+/-1.0 mg per deciliter [265.2+/-88.4 micromol per liter]) or isotonic-saline hydration at a rate of 1 ml per kilogram of body weight per hour given in a step-down unit (56 patients, with a mean serum creatinine concentration of 3.1+/-1.0 mg per deciliter [274.0+/-88.4 micromol per liter]). Hemofiltration (fluid replacement rate, 1000 ml per hour without weight loss) and saline hydration were initiated 4 to 8 hours before the coronary intervention and were continued for 18 to 24 hours after the procedure was completed.
RESULTS: An increase in the serum creatinine concentration of more than 25 percent from the base-line value after the coronary intervention occurred less frequently among the patients in the hemofiltration group than among the control patients (5 percent vs. 50 percent, P<0.001). Temporary renal-replacement therapy (hemodialysis or hemofiltration) was required in 25 percent of the control patients and in 3 percent of the patients in the hemofiltration group. The rate of in-hospital events was 9 percent in the hemofiltration group and 52 percent in the control group (P<0.001). In-hospital mortality was 2 percent in the hemofiltration group and 14 percent in the control group (P=0.02), and the cumulative one-year mortality was 10 percent and 30 percent, respectively (P=0.01).
CONCLUSIONS: In patients with chronic renal failure who are undergoing percutaneous coronary interventions, periprocedural hemofiltration given in an ICU setting appears to be effective in preventing the deterioration of renal function due to contrast-agent-induced nephropathy and is associated with improved in-hospital and long-term outcomes.

Copyright 2003 Massachusetts Medical Society
PMID 14523141  N Engl J Med. 2003 Oct 2;349(14):1333-40. doi: 10.1056/・・・
著者: Giancarlo Marenzi, Gianfranco Lauri, Jeness Campodonico, Ivana Marana, Emilio Assanelli, Monica De Metrio, Marco Grazi, Fabrizio Veglia, Franco Fabbiocchi, Piero Montorsi, Antonio L Bartorelli
雑誌名: Am J Med. 2006 Feb;119(2):155-62. doi: 10.1016/j.amjmed.2005.08.002.
Abstract/Text PURPOSE: Contrast-induced nephropathy is a complication of contrast medium administration during diagnostic and interventional procedures, with important prognostic relevance. Patients with chronic kidney disease have a higher risk for contrast-induced nephropathy and poorer outcome. In patients with chronic kidney disease, hemofiltration reduces contrast-induced nephropathy incidence and improves long-term survival. We assessed the mechanisms involved in the prophylactic effect of hemofiltration and of the most effective hemofiltration protocol to prevent contrast-induced nephropathy in patients with chronic kidney disease.
SUBJECTS AND METHODS: We randomized 92 patients with chronic kidney disease (creatinine clearance < or =30 mL/min) to three different prophylactic treatments: intravenous hydration with isotonic saline (1 mL x kg x h for 12 hours before and after contrast exposure, control group; n = 30); intravenous hydration for 12 hours before contrast exposure, followed by hemofiltration for 18 to 24 hours after contrast exposure (post-hemofiltration group; n = 31), and hemofiltration performed for 6 hours before and for 18 to 24 hours after contrast exposure (pre/post-hemofiltration group; n = 31). The incidence of contrast-induced nephropathy (>25% increase in creatinine) and the in-hospital clinical course were compared in the three groups.
RESULTS: Twelve patients (40%) in the control group, 8 patients (26%) in the post-hemofiltration group, and 1 patient (3%) in the pre/post-hemofiltration group experienced contrast-induced nephropathy (P = .0013); hemodialysis was required in 9 (30%), three (10%), and zero (0%) patients, respectively (P = .002). In-hospital mortality was 20%, 10%, and 0%, respectively (P = .03).
CONCLUSIONS: Hemofiltration is an effective strategy for contrast-induced nephropathy prevention in patients with chronic kidney disease who are undergoing cardiovascular procedures. Pre-hemofiltration is required to obtain the full clinical benefit, suggesting that, among different mechanisms possibly involved, high-volume controlled hydration before contrast media exposure plays a major role.

PMID 16443418  Am J Med. 2006 Feb;119(2):155-62. doi: 10.1016/j.amjmed・・・
著者: Dinna N Cruz, Ching Yan Goh, Giancarlo Marenzi, Valentina Corradi, Claudio Ronco, Mark A Perazella
雑誌名: Am J Med. 2012 Jan;125(1):66-78.e3. doi: 10.1016/j.amjmed.2011.06.029.
Abstract/Text BACKGROUND: Radiocontrast-induced nephropathy (RCIN) is an important cause of acute kidney injury, increasing in-hospital and long-term mortality. It is controversial whether prophylactic renal replacement therapy (RRT) may reduce a patient's risk of RCIN when compared with standard medical therapy (SMT).
METHODS: We searched through PubMed and bibliographies of retrieved articles. Published studies of RRT for RCIN prevention in patients receiving radiocontrast were included. The primary endpoint was RCIN incidence, defined as an increase in serum creatinine ≥0.5 mg/dL. Results were combined on the risk ratio (RR) scale. Random-effects models were used. Sensitivity analyses were defined a priori to evaluate the effects of RRT modality, study design, and sample size.
RESULTS: Nine randomized controlled and 2 nonrandomized trials were included (n = 1010 patients); 8 studies used hemodialysis (HD) and 3 used hemofiltration or hemodiafiltration. Nine studies had data for primary endpoint; RCIN incidence was 23.3% in the RRT group and 21.2% in SMT. RRT did not decrease RCIN incidence compared with SMT (risk ratio [RR] 1.02; 95% confidence interval [CI], 0.54-1.93); however, intertrial heterogeneity was high. In sensitivity analyses, limiting to only HD studies significantly reduced heterogeneity. HD appeared to increase RCIN risk (RR 1.61; 95% CI, 1.13-2.28) and had no effect on need for permanent RRT or progression to end-stage renal disease (RR 1.47; 95% CI, 0.56-3.89).
CONCLUSION: In this updated meta-analysis, periprocedural RRT did not decrease the incidence of RCIN compared with SMT. HD appears to actually increase RCIN risk.

Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 22195531  Am J Med. 2012 Jan;125(1):66-78.e3. doi: 10.1016/j.amjm・・・
著者: Hendrick B Barner, Marci Bailey, Tracey J Guthrie, Michael K Pasque, Marc R Moon, Ralph J Damiano, Jennifer S Lawton
雑誌名: Circulation. 2012 Sep 11;126(11 Suppl 1):S140-4. doi: 10.1161/CIRCULATIONAHA.111.081497.
Abstract/Text BACKGROUND: The radial artery is often used as the second arterial graft for coronary artery bypass grafting. Little is known about the differences in long-term patency between radial free and T grafts. This study was performed to determine long-term radial artery patency over a 15-year period.
METHODS AND RESULTS: Radial arteries were used as free grafts or T grafts for coronary artery bypass grafting over a 15-year period. Patients were contacted to determine if postoperative cardiac catheterization was performed and examination of any reports and films was performed. Grafts were graded as patent, luminal irregularity, or occluded. Each sequential graft was counted separately. Between September 1993 and December 2008, 13,926 patients underwent isolated coronary artery bypass grafting and 3248 patients had at least one radial artery graft used as a conduit. Catheterizations were performed at a mean of 7.4 ± 3.8 years (range, 3 days to 14.4 years) on 372 radial artery grafts (103 free and 269 T) in 215 patients. Kaplan-Meier freedom from occlusion for radial free and T grafts at 1 and 10 years was 97.1% and 75.4% and 99.6% and 62.9%, respectively (P=0.146 free versus T). Kaplan-Meier survival to 15 years was not statistically different between free and T graft patients (P=0.5).
CONCLUSIONS: In 215 patients with postoperative catheterization after coronary artery bypass grafting with a radial artery graft, radial free and T grafts had similar and acceptable long-term patency to support their use as a coronary artery bypass graft conduit.

PMID 22965974  Circulation. 2012 Sep 11;126(11 Suppl 1):S140-4. doi: 1・・・
著者: Ralf E Harskamp, Marcel A Beijk, Peter Damman, Wichert J Kuijt, Pier Woudstra, Maik J Grundeken, Jaap J Kloek, Jan G Tijssen, Bas A de Mol, Robbert J de Winter
雑誌名: J Cardiovasc Med (Hagerstown). 2013 Jun;14(6):438-45. doi: 10.2459/JCM.0b013e328356a4fc.
Abstract/Text AIMS: To describe long-term outcome following surgical and percutaneous revascularization in graft failure.
METHODS: We analyzed consecutive patients with graft failure after heart-team assignment to percutaneous coronary intervention (PCI) or redo coronary artery bypass grafting (CABG) between 2003 and 2008. The primary endpoint was the composite of death, myocardial infarction (MI) or target vessel revascularization (TVR). Kaplan-Meier event rate estimates were calculated up to a 5-year follow-up. Independent predictors for outcomes were identified by backward selection in a multivariable Cox proportional hazard model.
RESULTS: We identified 287 patients treated for graft failure: 243 with PCI and 44 with redo CABG. Patients undergoing PCI more frequently presented with ST-elevated myocardial infarction (STEMI) (P < 0.001), multivessel disease (P < 0.001), vein graft failure (P = 0.04), a history of MI (P < 0.001) and shorter time-to-graft failure (P = 0.001). Bare-metal stents (BMS) were used in 81.3% of the PCI-treated lesions and drug-eluting stents (DES) in 18.7%. The median follow-up was 3.9 years. Five-year rate of composite all-cause death, MI or TVR was 57.6% after PCI and 51% after CABG (P = 0.51). Repeat revascularization [TVR and target lesion revascularization (TLR)] was 30.7 and 21.3% after PCI, and 8.0 and 3.2% following CABG (P = 0.009; P = 0.008). In the PCI group, BMS was associated with higher rates of TVR (35.1 vs. 12.6%; P = 0.04) and TLR (24.8 vs. 7.6%; P = 0.04), but similar rate of death or MI compared with DES. Independent predictors for the primary outcome were creatinine [hazard ratio 1.008 per μmol/l, 95% confidence interval (CI) 1.005-1.011, P < 0.001] and peak creatine kinase MB (hazard ratio 1.001 per U/l, 95% CI 1.000-1.002, P = 0.027).
CONCLUSION: Clinical outcomes are similarly poor after heart-team triage for surgical or percutaneous intervention in patients with graft failure. Repeat revascularization occurred more frequent after PCI, particularly following BMS implantation.

PMID 22828774  J Cardiovasc Med (Hagerstown). 2013 Jun;14(6):438-45. d・・・
著者: T Horii, H Suma, Y Wanibuchi, S Fukuda, I Kigawa
雑誌名: Nihon Kyobu Geka Gakkai Zasshi. 1993 Sep;41(9):1447-51.
Abstract/Text While annual attrition and high break-down rate of saphenous vein graft (SVG) used for CABG has widely noted in Western countries, no sizable studies have yet available in Japan. We studied 142 SVGs of 77 pts, which we divided into two groups; 80 SVGs of 44 pts in mid-term period (5 to 8 years after surgery) and 62 SVGs of 33 pts in long-term period (9 to 17 years after surgery). The patency rate of SVGs was 69% in mid-term and 77% in long-term. Whereas these patency rates at each periods were superior to those reported from USA and European countries, a quarter of SVGs in mid-term period and a half in long-term period had significant stenotic changes (over 50%). Of patent SVGs, diseased SVGs reached 36% in mid-term period and 73% in long-term period. In conclusion, although the patency rate of SVGs in Japanese patients was higher than that of the Western countries, vein graft disease apparently occurred in a large proportion of patent SVGs.

PMID 8409597  Nihon Kyobu Geka Gakkai Zasshi. 1993 Sep;41(9):1447-51.・・・
著者: John H Alexander, Gail Hafley, Robert A Harrington, Eric D Peterson, T Bruce Ferguson, Todd J Lorenz, Abhinav Goyal, Michael Gibson, Michael J Mack, Daniel Gennevois, Robert M Califf, Nicholas T Kouchoukos, PREVENT IV Investigators
雑誌名: JAMA. 2005 Nov 16;294(19):2446-54. doi: 10.1001/jama.294.19.2446.
Abstract/Text CONTEXT: Coronary artery bypass graft (CABG) surgery with autologous vein grafting is commonly performed. Progressive neointimal hyperplasia, however, contributes to considerable vein graft failure. Edifoligide is an oligonucleotide decoy that binds to and inhibits E2F transcription factors and thus may prevent neointimal hyperplasia and vein graft failure.
OBJECTIVE: To assess the efficacy and safety of pretreating vein grafts with edifoligide for patients undergoing CABG surgery.
DESIGN, SETTING, AND PARTICIPANTS: A phase 3 randomized, double-blind, placebo-controlled trial of 3014 patients undergoing primary CABG surgery with at least 2 planned saphenous vein grafts and without concomitant valve surgery, who were enrolled between August 2002 and October 2003 at 107 US sites.
INTERVENTION: Vein grafts were treated ex vivo with either edifoligide or placebo in a pressure-mediated delivery system. The first 2400 patients enrolled were scheduled for 12- to 18-month follow-up angiography.
MAIN OUTCOME MEASURES: The primary efficacy end point was angiographic vein graft failure (> or =75% vein graft stenosis) occurring 12 to 18 months after CABG surgery. Other end points included other angiographic variables, adverse events through 30 days, and major adverse cardiac events.
RESULTS: A total of 1920 patients (80%) either died (n = 91) or underwent follow-up angiography (n = 1829). Edifoligide had no effect on the primary end point of per patient vein graft failure (436 [45.2%] of 965 patients in the edifoligide group vs 442 [46.3%] of 955 patients in the placebo group; odds ratio, 0.96 [95% confidence interval {CI}, 0.80-1.14]; P = .66), on any secondary angiographic end point, or on the incidence of major adverse cardiac events at 1 year (101 [6.7%] of 1508 patients in the edifoligide group vs 121 [8.1%] of 1506 patients in the placebo group; hazard ratio, 0.83 [95% CI, 0.64-1.08]; P = .16).
CONCLUSIONS: Failure of at least 1 vein graft is quite common within 12 to 18 months after CABG surgery. Edifoligide is no more effective than placebo in preventing these events. Longer-term follow-up and additional research are needed to determine whether edifoligide has delayed beneficial effects, to understand the mechanisms and clinical consequences of vein graft failure, and to improve the durability of CABG surgery. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT00042081.

PMID 16287955  JAMA. 2005 Nov 16;294(19):2446-54. doi: 10.1001/jama.29・・・
著者: James Tatoulis, Brian F Buxton, John A Fuller
雑誌名: Ann Thorac Surg. 2011 Jul;92(1):9-15; discussion 15-7. doi: 10.1016/j.athoracsur.2011.03.099.
Abstract/Text BACKGROUND: The right internal thoracic artery (RITA) is biologically identical to the left ITA, yet is rarely used in coronary artery bypass graft surgery (CABG). We examined the results and long-term patency of RITA grafts.
METHODS: Between 1986 and 2008, 991 consecutive RITA graft angiograms for postoperative cardiac symptoms were evaluated by two independent observers. Grafts were considered nonpatent if they had a greater than 80% stenosis, string sign, or total occlusion. Patency was examined over time by coronary territory, whether in situ or free RITA, and compared with other conduits. Clinical results were collected prospectively and by the National Death Index.
RESULTS: A total of 5,766 patients had a RITA graft as part of a bilateral ITA CABG procedure. Operative mortality was 1.1%; deep sternal infection 1.5%. Of 7,780 coronary conduits studied, 991 RITA conduits were examined; a mean of 100±60 months postoperatively (1 to 288 months). Overall ten-year RITA patency was 90%. The RITA graft patency to the left anterior descending artery (LAD; n=149) was 95% at 10 years and 90% at 15 years. Ten-year RITA patency to the circumflex marginal (Cx; n=436) was 91%, right coronary artery (n=199) was 84% (p<0.001), and posterior descending artery (n=207) was 86%. Ten-year RITA and LITA patencies to the LAD were identical (95% vs 96%) and to the Cx (91% vs 89%), respectively. In situ RITA (n=450) and free RITA (n=541) had similar ten-year patencies (89% vs 91%; p=0.44). The RITA patency was always better than the radial artery (p<0.01) and saphenous vein grafts (p<0.001). Atheromatous changes were not seen in the RITA angiograms. Ten-year survival of patients with RITA and LITA for triple-vessel coronary disease was 89%.
CONCLUSIONS: Late patencies of RITA are excellent, equivalent to the LITA for identical territories, always better than radial arteries and saphenous vein grafts, and remain free of atheroma. Use of RITA in addition to LITA is associated with excellent survival in triple-vessel coronary disease. More extensive use of the RITA in CABG is recommended.

Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
PMID 21718825  Ann Thorac Surg. 2011 Jul;92(1):9-15; discussion 15-7. ・・・
著者: Paul Achouh, Redha Boutekadjirt, Daniel Toledano, Nadjib Hammoudi, Jean-Yves Pagny, Pascal Goube, Khaled Ould Isselmou, Bernard Lancelin, Régis Fouquet, Christophe Acar
雑誌名: J Thorac Cardiovasc Surg. 2010 Jul;140(1):73-9, 79.e1-2. doi: 10.1016/j.jtcvs.2009.09.032. Epub 2009 Nov 26.
Abstract/Text OBJECTIVE: The aim of this study was to assess the angiographic results of the radial artery as a coronary bypass conduit at long term (>5 years).
METHODS: Radial artery grafts were controlled in 202 patients at 10.1 years by conventional angiography (n = 79) and computed tomography (n = 123). Clinical or paraclinical evidence of ischemia was noted in 81 patients, whereas 121 patients were asymptomatic. Some 520 conduits were controlled: radial artery (n = 230), left internal thoracic artery (n = 190), right internal thoracic artery (n = 30), and veins (n = 70). Radial arteries were anastomosed to the right coronary (24%), marginal (58%), diagonal (16%), and left anterior descending (<1%) arteries, whereas left internal thoracic arteries were primarily anastomosed to the left anterior descending artery (95%). The mean number of antithrombotic and anti-anginal medications was 1.2 and 1.9 per patient, respectively.
RESULTS: The ejection fraction was slightly decreased compared with its preoperative value (54% +/- 11% vs 57% +/- 9%; P = .009). Nine reoperations were required at 10.5 years for valve replacement (n = 8) and isolated bypass (n = 1). Percutaneous intervention was performed in 48 patients (24%) at 7.6 years on a graft (28%) or a native coronary artery (72%). The 10-year patency of radial artery grafts was 83%, which was lower than the patency of left internal thoracic arteries (95%, P < .001) and similar to the patency of right internal thoracic arteries (87%, P = .66) and veins (81%, P = .50). No medication seemed to influence radial artery graft patency (aspirin: P = .26; calcium blockers: P = .36). All graft patency was lower when clinical or paraclinical evidence of ischemia was present than in asymptomatic cases (83% vs 90% P = .02). The patency of left anterior descending grafts was higher than that of non-left anterior descending grafts (96% vs 82% P < .001).
CONCLUSION: The radial artery-to-coronary bypass conduit provided a low coronary reoperation rate with an excellent patency (83%) up to 20 years postoperatively.

2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
PMID 19944433  J Thorac Cardiovasc Surg. 2010 Jul;140(1):73-9, 79.e1-2・・・
著者: Joseph F Sabik, Eugene H Blackstone, Penny L Houghtaling, Peter A Walts, Bruce W Lytle
雑誌名: Ann Thorac Surg. 2005 Nov;80(5):1719-27. doi: 10.1016/j.athoracsur.2005.04.033.
Abstract/Text BACKGROUND: Hospital mortality for reoperative coronary artery bypass grafting (CABG) is approaching that of primary CABG. This raises two questions: (1) has experience neutralized the risk of reoperation attributable to its greater difficulty, or (2) has experience neutralized the risk attributable to the higher-risk profile of reoperative patients?.
METHODS: From 1990 to 2003, 21,568 CABG procedures were performed, of which 4,518 (21%) were reoperations: 3,919 first, 552 second, 43 third, 3 fourth, and 1 fifth. Reoperative patients had a higher-risk profile than primary patients, with more vascular disease, left ventricular dysfunction, and coronary artery disease (all p < 0.0001). Logistic regression was used to identify factors associated with hospital death and to develop a propensity score for reoperation, which was used to (1) adjust multivariable analyses of death and (2) compare outcomes in matched patients.
RESULTS: Hospital mortality was 4.3% (168 of 3,919) for first reoperation, 5.1% (28 of 552) for second, and 6.4% (3 of 47) for third or more, compared with 1.5% (263 of 17,050) for primary operations. Risk of both primary and reoperative CABG decreased with experience (p > 0.0002); however, reoperative risk fell markedly in the mid-1990s. In both the overall and matched-pairs analyses, reoperation was a risk factor before 1997 (p < or = 0.008), but not after (p = 0.2). Reoperation within 1 year of previous CABG increased risk (p < 0.0001). Risk attributable to left ventricular dysfunction decreased with experience (p = 0.05).
CONCLUSIONS: Hospital mortality for reoperative CABG has been consistently higher than for primary operation, but this difference has narrowed considerably. Patient characteristics, not reoperation itself, now have greater influence.

PMID 16242445  Ann Thorac Surg. 2005 Nov;80(5):1719-27. doi: 10.1016/j・・・
著者: M A Borger, G Cohen, K J Buth, V Rao, J Bozinovski, N Liaghati-Nasseri, H Mallidi, R Feder-Elituv, J Sever, G T Christakis, G Bhatnagar, B S Goldman, E A Cohen, S E Fremes
雑誌名: Circulation. 1998 Nov 10;98(19 Suppl):II7-13; discussion II13-4.
Abstract/Text BACKGROUND: Left internal thoracic artery (LITA) grafts to the left anterior descending coronary artery (LAD) during coronary bypass surgery (CABG) have greater patency rates than saphenous vein grafts and reduce long-term cardiac morbidity and mortality rates. The benefits of multiple versus single arterial grafts and the role of different arterial conduits with respect to short- and medium-term outcome remains controversial. The purpose of this study was to compare the perioperative and intermediate-term results of: (1) patients receiving 2 arterial grafts versus 1 arterial graft and (2) patients receiving a right internal thoracic artery (RITA) versus a radial artery (RA) as the second arterial graft.
METHODS AND RESULTS: Retrospective analysis of prospectively gathered data on consecutive patients undergoing isolated CABG at our institution between 1989 and 1996 was conducted. The first section of the study compared outcomes for 1 arterial graft (LITA to LAD, n = 2333) versus 2 arterial grafts (LITA + RA or LITA + RITA, n = 378). The second section of the study compared outcomes for the RITA (n = 132) versus the RA (n = 171) as second arterial grafts since 1992, when the radial series was initiated. Part I: By multivariable stepwise logistic regression, the use of 1 arterial graft was associated with an increased incidence of perioperative cardiac morbidity and mortality (odds ratio 2.2, 95% confidence interval 1.4 to 3.3), with the use of our current patient selection criteria. Double-arterial graft patients had a nonsignificant trend toward increased intermediate-term actuarial survival (P = 0.12) and cardiac event-free survival (P = 0.09). Part II: Comparison of preoperative demographics revealed a higher incidence of diabetes (27% vs 11%, P < 0.001), peripheral vascular disease (16% vs 8%, P = 0.03), and elderly age (13% vs 2%, P = 0.001) in patients receiving an RA versus those receiving a RITA as the second arterial graft. Perioperative outcome analysis revealed a decreased intensive care unit stay in the RA versus RITA group (median 30.4 vs 36.2 hours, respectively, P = 0.005) but no significant difference in hospital length of stay. There was no significant difference in perioperative mortality or cardiac morbidity rates. RITA patients had a higher incidence of sternal wound infection (5.3% vs 0.6%, P = 0.01), however, and tended to have increased blood product transfusion rates (51% vs 40%, P = 0.06).
CONCLUSIONS: The use of 2 arterial grafts is safe, with a reduction in perioperative cardiac morbidity or mortality rates compared with 1 arterial graft after adjustment for other risk variables. When comparing RITA to RA as second arterial grafts, patients receiving an RA have a lower incidence of sternal wound infection and decreased transfusion requirements, with no difference in perioperative or intermediate-term cardiac morbidity or mortality rates.

PMID 9852873  Circulation. 1998 Nov 10;98(19 Suppl):II7-13; discussio・・・
著者: Nimesh D Desai, Eric A Cohen, C David Naylor, Stephen E Fremes, Radial Artery Patency Study Investigators
雑誌名: N Engl J Med. 2004 Nov 25;351(22):2302-9. doi: 10.1056/NEJMoa040982.
Abstract/Text BACKGROUND: In the past decade, the radial artery has frequently been used for coronary bypass surgery despite concern regarding the possibility of graft spasm. Graft patency is a key predictor of long-term survival. We therefore sought to determine the relative patency rate of radial-artery and saphenous-vein grafts in a randomized trial in which we controlled for bias in the selection of patients and vessels.
METHODS: We enrolled 561 patients at 13 centers. The left internal thoracic artery was used to bypass the anterior circulation. The radial-artery graft was randomly assigned to bypass the major vessel in either the inferior (right coronary) territory or the lateral (circumflex) territory, with the saphenous-vein graft used for the opposing territory (control). The primary end point was graft occlusion, determined by angiography 8 to 12 months postoperatively.
RESULTS: Angiography was performed at one year in 440 patients: 8.2 percent of radial-artery grafts and 13.6 percent of saphenous-vein grafts were completely occluded (P=0.009). Diffuse narrowing of the graft (the angiographic "string sign") was present in 7.0 percent of radial-artery grafts and only 0.9 percent of saphenous-vein grafts (P=0.001). The absence of severe native-vessel stenosis was associated with an increased risk of occlusion of the radial-artery graft and diffuse narrowing of the graft. Harvesting of the radial artery was well tolerated.
CONCLUSIONS: Radial-artery grafts are associated with a lower rate of graft occlusion at one year than are saphenous-vein grafts. Because the patency of radial-artery grafts depends on the severity of native-vessel stenosis, such grafts should preferentially be used for target vessels with high-grade lesions.

Copyright 2004 Massachusetts Medical Society.
PMID 15564545  N Engl J Med. 2004 Nov 25;351(22):2302-9. doi: 10.1056/・・・
著者: Cheng-Hon Yap, Luigi Sposato, Enoch Akowuah, Sanjay Theodore, Diem T Dinh, Gilbert C Shardey, Peter D Skillington, James Tatoulis, Michael Yii, Julian A Smith, Morteza Mohajeri, Adrian Pick, Siven Seevanayagam, Christopher M Reid
雑誌名: Ann Thorac Surg. 2009 May;87(5):1386-91. doi: 10.1016/j.athoracsur.2009.02.006.
Abstract/Text BACKGROUND: Reoperative coronary artery bypass grafting (redo CABG) shows improving outcomes, but with varying degrees of improvement. We assessed contemporary outcomes after redo CABG to determine if redo status is still a risk factor for early postoperative complications and midterm survival.
METHODS: Isolated CABG procedures (June 1, 2001 to May 31, 2008) within the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database were included. Redo status as a predictor for early outcomes was assessed with logistic regression analysis. Midterm survival was determined from the National Death Index. Effect of redo status on midterm survival was assessed using a Cox proportional hazards model.
RESULTS: Inclusion criteria were met by 13,436 patients, and 458 (3.4%) underwent redo CABG. Operative mortality was 4.8% for redo CABG and 1.8% for first-time CABG (p < 0.001). After adjustment, redo status remained a predictor for operative mortality (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3 to 3.6), myocardial infarction (OR, 2.8; 95% CI, 1.6 to 6.0), and prolonged ventilation (OR, 1.5; 95% CI, 1.1 to 2.0). Unadjusted survival was lower for the redo CABG group vs the first-time CABG group at up to 6 years (p = 0.01, log-rank test. After adjusting for differences in patient variables, redo status was not a predictor of midterm survival (OR, 1.03; 95% CI, 0.78 to 1.35; p = 0.85).
CONCLUSIONS: Early postoperative outcomes of redo CABG are encouraging. Midterm survival is excellent; however, redo remains a significant risk factor for operative mortality in contemporary practice.

PMID 19379870  Ann Thorac Surg. 2009 May;87(5):1386-91. doi: 10.1016/j・・・
著者: Douglass A Morrison, Gulshan Sethi, Jerome Sacks, William G Henderson, Frederick Grover, Steven Sedlis, Rick Esposito, Investigators of the Department of Veterans Affairs Cooperative Study #385, Angina With Extremely Serious Operative Mortality Evaluation
雑誌名: J Am Coll Cardiol. 2002 Dec 4;40(11):1951-4.
Abstract/Text OBJECTIVES: This report compares long-term percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) survival among post-CABG patients included in the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial and prospective registry.
BACKGROUND: Repeat CABG surgery is associated with a higher risk of mortality than first-time CABG. The AWESOME is the first randomized trial comparing CABG with PCI to include post-CABG patients.
METHODS: Over a five-year period (1995 to 2000), patients at 16 hospitals were screened to identify a cohort of 2,431 individuals who had medically refractory myocardial ischemia and at least one of five high-risk factors. There were 454 patients in the randomized trial, of whom 142 had prior CABG. In the physician-directed registry of 1,650 patients, 719 had prior CABG. Of the 327 patient-choice registry patients, 119 had at least one prior CABG. The CABG and PCI survivals for the three groups were compared using Kaplan-Meier curves and log-rank tests.
RESULTS: The CABG and PCI three-year survival rates were 73% and 76% respectively for the 142 randomized patients (75 and 67 patients) (log-rank = NS). In the physician-directed registry, 155 patients were assigned to reoperation and 357 to PCI (207 received medical therapy); 36-month survivals were 71% and 77% respectively (log-rank = NS). In the patient-choice registry, 32 patients chose reoperation and 74 chose PCI (13 received medical therapy); 36-month survivals were 65% and 86% respectively (log-rank test p = 0.01).
CONCLUSIONS: Percutaneous coronary intervention is preferable to CABG for many post-CABG patients.

PMID 12475454  J Am Coll Cardiol. 2002 Dec 4;40(11):1951-4.
著者: Hisayoshi Suma, Hiroaki Tanabe, Akihito Takahashi, Taiko Horii, Tadashi Isomura, Hitoshi Hirose, Atsushi Amano
雑誌名: Circulation. 2007 Sep 11;116(11 Suppl):I188-91. doi: 10.1161/CIRCULATIONAHA.106.678813.
Abstract/Text BACKGROUND: To improve the longterm outcome after CABG, several strategies have been used using arterial conduits. Our 20 years experience with the right gastroepiploic artery (GEA) graft was evaluated.
METHODS AND RESULTS: In 1352 patients having CABG with the GEA graft, (1092 men, mean 63 years, 99% multivessel disease, and mean EF 0.51), internal thoracic artery, saphenous vein, and radial artery grafts were concomitantly used in 1312 (97%), 783 (58%), and 128 (8%) patients, respectively. The mean number of distal anastomoses was 3.1, and 2.4 coronary arteries were bypassed with arterial grafts. The sites for GEA grafting were 70 anterior descending, 268 circumflex, and 1089 right coronary arteries. The operative mortality was 1.26%. In 1118 follow-up patients (82.6%), 5, 10, and 15 years survival rates were 91.7%, 81.4%, and 71.3%, and the cardiac death-free survival rates were 95.8%, 91.7%, and 88.6%, respectively. The cumulative patency rate of the GEA graft was 97.1% at 1 month, 92.3% at 1 year, 85.5% at 5 years, and 66.5% at 10 years, respectively. In 172 skeletonized GEA grafts with 233 distal anastomoses, the patency rate at immediate, 1, and 4 years after surgery was 97.6%, 92.9%, and 86.4%, respectively. In 124 patients with late (5 to 17 years) restudy, patency rate was 96% (114/119) in the left internal thoracic artery, 87% (108/124) in GEA, and 68% (67/98) in saphenous vein grafts. New stenosis was uncommon in GEA.
CONCLUSION: The GEA graft is a safe and effective arterial conduit for CABG.

PMID 17846302  Circulation. 2007 Sep 11;116(11 Suppl):I188-91. doi: 10・・・
著者: F W Bär, F W Verheugt, J Col, P Materne, J P Monassier, P G Geslin, J Metzger, P Raynaud, J Foucault, C de Zwaan
雑誌名: Circulation. 1992 Jul;86(1):131-7.
Abstract/Text BACKGROUND: The value of thrombolytic therapy in unstable angina is unclear.
METHODS AND RESULTS: To study this problem, 159 patients were studied in a double-blind, placebo-controlled multicenter trial. Patients without a previous myocardial infarction, with a typical history of unstable angina, and ECG abnormalities indicative of ischemia were included. After baseline angiography, study medication (anistreplase or placebo) was given. Angiography was repeated after 12-28 hours. A significant decrease occurred in diameter stenosis between the first and second angiogram in the anistreplase group compared with the placebo group (11% versus 3%, p = 0.008). This difference was caused by reopening of occluded vessels in the thrombolytic group. However, no beneficial clinical effects of thrombolytic treatment were found. Bleeding complications were significantly higher in patients who received thrombolytic therapy (21 versus seven patients, p = 0.001).
CONCLUSIONS: Thus, angiographic but no clinical improvement after thrombolytic treatment with anistreplase was found in patients with unstable angina with an excess of bleeding complications. Therefore, thrombolytic treatment cannot be recommended in patients diagnosed as having unstable angina until proven otherwise.

PMID 1617766  Circulation. 1992 Jul;86(1):131-7.
著者:
雑誌名: Circulation. 1994 Apr;89(4):1545-56.
Abstract/Text BACKGROUND: Although coronary thrombosis plays a critical role in the pathogenesis of unstable angina and non-Q-wave myocardial infarction (NQMI), the effects of thrombolytic therapy in these disorders is not clear. Also, the role of routine early coronary arteriography followed by revascularization has not been established.
METHODS AND RESULTS: Patients (n = 1473) seen within 24 hours of ischemic chest discomfort at rest, considered to represent unstable angina or NQMI, were randomized using a 2 x 2 factorial design to compare (1) TPA versus placebo as initial therapy and (2) an early invasive strategy (early coronary arteriography followed by revascularization when the anatomy was suitable) versus an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients were treated with bed rest, anti-ischemic medications, aspirin, and heparin. The primary end point for the TPA-placebo comparison (death, myocardial infarction, or failure of initial therapy at 6 weeks) occurred in 54.2% of the TPA-treated patients and 55.5% of the placebo-treated patients (P = NS). Fatal and nonfatal myocardial infarction after randomization (reinfarction in NQMI patients) occurred more frequently in TPA-treated patients (7.4%) than in placebo-treated patients (4.9%, P = .04, Kaplan-Meier estimate). Four intracranial hemorrhages occurred in the TPA-treated group versus none in the placebo-treated group (P = .06). The end point for the comparison of the two strategies (death, myocardial infarction, or an unsatisfactory symptom-limited exercise stress test at 6 weeks) occurred in 18.1% of patients assigned to the early conservative strategy and 16.2% of patients assigned to the early invasive strategy (P = NS). In the latter, the average length of initial hospitalization, incidence of rehospitalization within 6 weeks, and days of rehospitalization all were significantly lower.
CONCLUSIONS: In the overall trial, patients with unstable angina and NQMI were managed with low rates of mortality (2.4%) and myocardial infarction or reinfarction (6.3%) at the time of the 6-week visit. These results can be achieved using either an early conservative or early invasive strategy, the latter resulting in a reduced incidence of days of hospitalization and of rehospitalization and in the use of antianginal drugs. The addition of a thrombolytic agent is not beneficial and may be harmful.

PMID 8149520  Circulation. 1994 Apr;89(4):1545-56.
著者: Julia A Critchley, Simon Capewell
雑誌名: JAMA. 2003 Jul 2;290(1):86-97. doi: 10.1001/jama.290.1.86.
Abstract/Text CONTEXT: As more interventions become available for the treatment of coronary heart disease (CHD), policy makers and health practitioners need to understand the benefits of each intervention, to better determine where to focus resources. This is particularly true when a patient with CHD quits smoking.
OBJECTIVE: To conduct a systematic review to determine the magnitude of risk reduction achieved by smoking cessation in patients with CHD.
DATA SOURCES: Nine electronic databases were searched from start of database to April 2003, supplemented by cross-checking references, contact with experts, and with large international cohort studies (identified by the Prospective Studies Collaboration).
STUDY SELECTION: Prospective cohort studies of patients who were diagnosed with CHD were included if they reported all-cause mortality and had at least 2 years of follow-up. Smoking status had to be measured after CHD diagnosis to ascertain quitting.
DATA EXTRACTION: Two reviewers independently assessed studies to determine eligibility, quality assessment of studies, and results, and independently carried out data extraction using a prepiloted, standardized form.
DATA SYNTHESIS: From the literature search, 665 publications were screened and 20 studies were included. Results showed a 36% reduction in crude relative risk (RR) of mortality for patients with CHD who quit compared with those who continued smoking (RR, 0.64; 95% confidence interval [CI], 0.58-0.71). Results from individual studies did not vary greatly despite many differences in patient characteristics, such as age, sex, type of CHD, and the years in which studies took place. Adjusted risk estimates did not differ substantially from crude estimates. Many studies did not adequately address quality issues, such as control of confounding, and misclassification of smoking status. However, restriction to 6 higher-quality studies had little effect on the estimate (RR, 0.71; 95% CI, 0.65-0.77). Few studies included large numbers of elderly persons, women, ethnic minorities, or patients from developing countries.
CONCLUSIONS: Quitting smoking is associated with a substantial reduction in risk of all-cause mortality among patients with CHD. This risk reduction appears to be consistent regardless of age, sex, index cardiac event, country, and year of study commencement.

PMID 12837716  JAMA. 2003 Jul 2;290(1):86-97. doi: 10.1001/jama.290.1.・・・
著者: J A Iestra, D Kromhout, Y T van der Schouw, D E Grobbee, H C Boshuizen, W A van Staveren
雑誌名: Circulation. 2005 Aug 9;112(6):924-34. doi: 10.1161/CIRCULATIONAHA.104.503995.
Abstract/Text BACKGROUND: Guidelines for lifestyle and dietary modification in patients with coronary artery disease (CAD) are mainly supported by evidence from general population studies. CAD patients, however, differ from the general population in age (older) and treatment with preventive drugs. This review seeks to provide evidence for a prognostic benefit of lifestyle and dietary recommendations from studies in CAD patients.
METHODS AND RESULTS: A literature search was performed on the effect of lifestyle and dietary changes on mortality in CAD patients. Prospective cohort studies and randomized controlled trials of patients with established CAD were included if they reported all-causes mortality and had at least 6 months of follow-up. The effect estimates of smoking cessation (relative risk [RR], 0.64; 95% CI, 0.58 to 0.71), increased physical activity (RR, 0.76; 95% CI, 0.59 to 0.98), and moderate alcohol use (RR, 0.80; 95% CI, 0.78 to 0.83) were studied most extensively. For the 6 dietary goals, data were too limited to provide reliable effect size estimates. Combinations of dietary changes were associated with reduced mortality (RR, 0.56; 95% CI, 0.42 to 0.74).
CONCLUSIONS: Available studies show convincingly the health benefits of lifestyle changes in CAD patients. Effect estimates of combined dietary changes look promising. Future studies should confirm these findings and assess the contribution of the individual dietary factors.

PMID 16087812  Circulation. 2005 Aug 9;112(6):924-34. doi: 10.1161/CIR・・・
著者: Cholesterol Treatment Trialists’ (CTT) Collaboration, C Baigent, L Blackwell, J Emberson, L E Holland, C Reith, N Bhala, R Peto, E H Barnes, A Keech, J Simes, R Collins
雑誌名: Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8.
Abstract/Text BACKGROUND: Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy.
METHODS: We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation.
FINDINGS: In the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11-18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7-19; p<0·0001), in coronary revascularisation of 19% (95% CI 15-24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5-26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76-0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR 0·90, 95% CI 0·87-0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74-0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81-0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84-1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81-1·18; p=0·8). No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92-1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96-1·04; p=0·9), even at low LDL cholesterol concentrations.
INTERPRETATION: Further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2-3 mmol/L would reduce risk by about 40-50%.
FUNDING: UK Medical Research Council, British Heart Foundation, European Community Biomed Programme, Australian National Health and Medical Research Council, and National Heart Foundation.

Copyright © 2010 Elsevier Ltd. All rights reserved.
PMID 21067804  Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S01・・・
著者: Christopher P Cannon, Eugene Braunwald, Carolyn H McCabe, Daniel J Rader, Jean L Rouleau, Rene Belder, Steven V Joyal, Karen A Hill, Marc A Pfeffer, Allan M Skene, Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators
雑誌名: N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8.
Abstract/Text BACKGROUND: Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear.
METHODS: We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24).
RESULTS: The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan-Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen.
CONCLUSIONS: Among patients who have recently had an acute coronary syndrome, an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.

Copyright 2004 Massachusetts Medical Society
PMID 15007110  N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056・・・
著者: John C LaRosa, Scott M Grundy, David D Waters, Charles Shear, Philip Barter, Jean-Charles Fruchart, Antonio M Gotto, Heiner Greten, John J P Kastelein, James Shepherd, Nanette K Wenger, Treating to New Targets (TNT) Investigators
雑誌名: N Engl J Med. 2005 Apr 7;352(14):1425-35. doi: 10.1056/NEJMoa050461. Epub 2005 Mar 8.
Abstract/Text BACKGROUND: Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD).
METHODS: A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke.
RESULTS: The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality.
CONCLUSIONS: Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.

Copyright 2005 Massachusetts Medical Society.
PMID 15755765  N Engl J Med. 2005 Apr 7;352(14):1425-35. doi: 10.1056/・・・
著者: Yuquing Zhang, Xuezhong Zhang, Lisheng Liu, Alberto Zanchetti, FEVER Study Group
雑誌名: Eur Heart J. 2011 Jun;32(12):1500-8. doi: 10.1093/eurheartj/ehr039. Epub 2011 Feb 22.
Abstract/Text AIMS: Major guidelines recommend lowering systolic blood pressure (SBP) to <140 mmHg in all hypertensives, but evidence is missing whether this is beneficial in (i) uncomplicated hypertensives, (ii) grade 1 hypertensives, and (iii) elderly hypertensives. Providing this missing evidence is important to justify efforts and costs of aggressive therapy in all hypertensives.
METHODS AND RESULTS: Felodipine Event Reduction (FEVER) was a double-blind, randomized trial on 9711 Chinese hypertensives, in whom cardiovascular outcomes were significantly reduced by more intense therapy (low-dose hydrochlorothiazide and low-dose felodipine) achieving a mean of 138 mmHg SBP compared with less-intense therapy (low-dose hydrochlorothiazide and placebo) achieving a mean of 142 mmHg. FEVER included older and younger patients, and patients with and without diabetes or cardiovascular disease. In the analyses here reported, Cox regression models assessed outcome differences between more and less-intense treatments in groups of patients with different baseline characteristics. Significant reductions in stroke were found in uncomplicated hypertensives (-39%, P = 0.002), in hypertensives with randomization SBP <153 mmHg (-29%, P = 0.03), and in elderly hypertensives (-44%, P < 0.001), when their SBP was lowered by more intense treatment. Significant reductions (between -29 and -47%, P = 0.02 to <0.001) were also found in all cardiovascular events and all deaths. Achieving mean SBP values <140 mmHg by adding a small dose of a generic drug prevented 2.1 (uncomplicated hypertensives) and 5.2 (elderly) cardiovascular events every 100 patients treated for 3.3 years.
CONCLUSIONS: These analyses provide strong support, missing so far, to guidelines recommending goal SBP <140 mmHg in uncomplicated hypertensives, individuals with moderately elevated BP and elderly hypertensives.

PMID 21345850  Eur Heart J. 2011 Jun;32(12):1500-8. doi: 10.1093/eurhe・・・
著者: Philip A Poole-Wilson, Jacobus Lubsen, Bridget-Anne Kirwan, Fred J van Dalen, Gilbert Wagener, Nicolas Danchin, Hanjörg Just, Keith A A Fox, Stuart J Pocock, Tim C Clayton, Michael Motro, John D Parker, Martial G Bourassa, Anthony M Dart, Per Hildebrandt, Ake Hjalmarson, Johannes A Kragten, G Peter Molhoek, Jan-Erik Otterstad, Ricardo Seabra-Gomes, Jordi Soler-Soler, Simon Weber, Coronary disease Trial Investigating Outcome with Nifedipine gastrointestinal therapeutic system investigators
雑誌名: Lancet. 2004 Sep 4-10;364(9437):849-57. doi: 10.1016/S0140-6736(04)16980-8.
Abstract/Text BACKGROUND: Calcium antagonists are widely prescribed for angina pectoris but their effect on clinical outcome is controversial. We aimed to investigate the effect of the calcium antagonist nifedipine on long-term outcome in patients with stable angina pectoris.
METHODS: We randomly assigned 3825 patients with treated stable symptomatic coronary disease to double-blind addition of nifedipine GITS (gastrointestinal therapeutic system) 60 mg once daily and 3840 to placebo. The primary endpoint was the combination of death, acute myocardial infarction, refractory angina, new overt heart failure, debilitating stroke, and peripheral revascularisation. Mean follow-up was 4.9 years (SD 1.1). Analysis was by intention to treat.
FINDINGS: 310 patients allocated nifedipine died (1.64 per 100 patient-years) compared with 291 people allocated placebo (1.53 per 100 patient-years; hazard ratio 1.07 [95% CI 0.91-1.25], p=0.41). Primary endpoint rates were 4.60 per 100 patient-years for nifedipine and 4.75 per 100 patient-years for placebo (0.97 [0.88-1.07], p=0.54). With nifedipine, rate of death and any cardiovascular event or procedure was 9.32 per 100 patient-years versus 10.50 per 100 patient-years for placebo (0.89 [0.83-0.95], p=0.0012). The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine, despite an increase in peripheral revascularisation. Nifedipine had no effect on the rate of myocardial infarction.
INTERPRETATION: Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival. Nifedipine GITS is safe and reduces the need for coronary angiography and interventions.

PMID 15351192  Lancet. 2004 Sep 4-10;364(9437):849-57. doi: 10.1016/S0・・・
著者: Alberto Zanchetti, Guido Grassi, Giuseppe Mancia
雑誌名: J Hypertens. 2009 May;27(5):923-34. doi: 10.1097/HJH.0b013e32832aa6b5.
Abstract/Text The evidence for two recommendations of all major guidelines on hypertension is critically discussed. The first recommendation is that of initiating antihypertensive drug treatment when systolic blood pressure is at least 140 or diastolic blood pressure at least 90 mmHg in patients with grade 1 hypertension and low or moderate total cardiovascular risk, and even when blood pressure is in the high normal range in patients with diabetes and previous cardiovascular disease. The second recommendation is that of achieving systolic blood pressure levels below 140 mmHg in all hypertensive patients, including the elderly, and values below 130 mmHg in patients having diabetes and high/very-high-risk patients. Critical analyses of the results of available trials show that the evidence is scanty for both recommendations. Nonetheless, they can be accepted as prudent statements, as antihypertensive agents are very well tolerated and lowering systolic blood pressure below 130 mmHg appears well tolerated. However, wisdom should not be taken for evidence, and simple trials should be designed to look for more solid evidence in favour of current recommendations.

PMID 19381107  J Hypertens. 2009 May;27(5):923-34. doi: 10.1097/HJH.0b・・・
著者: L Hansson, A Zanchetti, S G Carruthers, B Dahlöf, D Elmfeldt, S Julius, J Ménard, K H Rahn, H Wedel, S Westerling
雑誌名: Lancet. 1998 Jun 13;351(9118):1755-62.
Abstract/Text BACKGROUND: Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.
METHODS: 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo.
FINDINGS: Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001).
INTERPRETATION: Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.

PMID 9635947  Lancet. 1998 Jun 13;351(9118):1755-62.
著者: V F Froelicher, K G Lehmann, R Thomas, S Goldman, D Morrison, R Edson, P Lavori, J Myers, C Dennis, R Shabetai, D Do, J Froning
雑誌名: Ann Intern Med. 1998 Jun 15;128(12 Pt 1):965-74.
Abstract/Text BACKGROUND: Empirical scores, computerized ST-segment measurements, and equations have been proposed as tools for improving the diagnostic performance of the exercise test.
OBJECTIVE: To compare the diagnostic utility of these scores, measurements, and equations with that of visual ST-segment measurements in patients with reduced workup bias.
DESIGN: Prospective analysis.
SETTING: 12 university-affiliated Veterans Affairs Medical Centers.
PATIENTS: 814 consecutive patients who presented with angina pectoris and agreed to undergo both exercise testing and coronary angiography.
MEASUREMENTS: Digital electrocardiographic recorders and angiographic calipers were used for testing at each site, and test results were sent to core laboratories.
RESULTS: Although 25% of patients had previously had testing, workup bias was reduced, as shown by comparison with a pilot study group. This reduction resulted in a sensitivity of 45% and a specificity of 85% for visual analysis. Computerized measurements and visual analysis had similar diagnostic power. Equations incorporating nonelectrocardiographic variables and either visual or computerized ST-segment measurement had similar discrimination and were superior to single ST-segment measurements. These equations correctly classified 5 more patients of every 100 tested (areas under the receiver-operating characteristic curve, 0.80 for equations and 0.68 for visual analysis; P < 0.001) in this population with a 50% prevalence of disease.
CONCLUSIONS: Standard exercise tests had lower sensitivity but higher specificity in this population with reduced work-up bias than in previous studies. Computerized ST-segment measurements were similar to visual ST-segment measurements made by cardiologists. Considering more than ST-segment measurements can enhance the diagnostic power of the exercise test.

PMID 9625682  Ann Intern Med. 1998 Jun 15;128(12 Pt 1):965-74.
著者:
雑誌名: Lancet. 1998 Sep 12;352(9131):837-53.
Abstract/Text BACKGROUND: Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.
METHODS: 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy.
FINDINGS: Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).
INTERPRETATION: Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)

PMID 9742976  Lancet. 1998 Sep 12;352(9131):837-53.
著者:
雑誌名: N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.
Abstract/Text BACKGROUND: Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.
METHODS: A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.
RESULTS: In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.
CONCLUSIONS: Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

PMID 8366922  N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/・・・
著者: Carlo Patrono, Felicita Andreotti, Harald Arnesen, Lina Badimon, Colin Baigent, Jean-Philippe Collet, Raffaele De Caterina, Dietrich Gulba, Kurt Huber, Steen Husted, Steen Dalby Kristensen, João Morais, Franz-Josef Neumann, Lars Hvilsted Rasmussen, Agneta Siegbahn, Philippe-Gabriel Steg, Robert F Storey, Frans Van de Werf, Freek Verheugt
雑誌名: Eur Heart J. 2011 Dec;32(23):2922-32. doi: 10.1093/eurheartj/ehr373. Epub 2011 Oct 20.
Abstract/Text The clinical pharmacology of antiplatelet drugs has been reviewed previously by the European Society of Cardiology (ESC) Task force and by the 8th American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. Moreover, information on the efficacy and safety of antiplatelet drugs in the treatment and prevention of atherothrombosis is provided by collaborative meta-analyses of 287 secondary prevention trials and 6 primary prevention trials. The present document intends to provide practicing physicians with an updated instrument to guide their choice of the most suitable antiplatelet strategy for the individual patient at risk, or with different clinical manifestations, of atherothrombosis.

PMID 22019823  Eur Heart J. 2011 Dec;32(23):2922-32. doi: 10.1093/eurh・・・
著者: Antithrombotic Trialists' (ATT) Collaboration, Colin Baigent, Lisa Blackwell, Rory Collins, Jonathan Emberson, Jon Godwin, Richard Peto, Julie Buring, Charles Hennekens, Patricia Kearney, Tom Meade, Carlo Patrono, Maria Carla Roncaglioni, Alberto Zanchetti
雑誌名: Lancet. 2009 May 30;373(9678):1849-60. doi: 10.1016/S0140-6736(09)60503-1.
Abstract/Text BACKGROUND: Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention.
METHODS: We undertook meta-analyses of serious vascular events (myocardial infarction, stroke, or vascular death) and major bleeds in six primary prevention trials (95,000 individuals at low average risk, 660,000 person-years, 3554 serious vascular events) and 16 secondary prevention trials (17,000 individuals at high average risk, 43,000 person-years, 3306 serious vascular events) that compared long-term aspirin versus control. We report intention-to-treat analyses of first events during the scheduled treatment period.
FINDINGS: In the primary prevention trials, aspirin allocation yielded a 12% proportional reduction in serious vascular events (0.51% aspirin vs 0.57% control per year, p=0.0001), due mainly to a reduction of about a fifth in non-fatal myocardial infarction (0.18%vs 0.23% per year, p<0.0001). The net effect on stroke was not significant (0.20%vs 0.21% per year, p=0.4: haemorrhagic stroke 0.04%vs 0.03%, p=0.05; other stroke 0.16%vs 0.18% per year, p=0.08). Vascular mortality did not differ significantly (0.19%vs 0.19% per year, p=0.7). Aspirin allocation increased major gastrointestinal and extracranial bleeds (0.10%vs 0.07% per year, p<0.0001), and the main risk factors for coronary disease were also risk factors for bleeding. In the secondary prevention trials, aspirin allocation yielded a greater absolute reduction in serious vascular events (6.7%vs 8.2% per year, p<0.0001), with a non-significant increase in haemorrhagic stroke but reductions of about a fifth in total stroke (2.08%vs 2.54% per year, p=0.002) and in coronary events (4.3%vs 5.3% per year, p<0.0001). In both primary and secondary prevention trials, the proportional reductions in the aggregate of all serious vascular events seemed similar for men and women.
INTERPRETATION: In primary prevention without previous disease, aspirin is of uncertain net value as the reduction in occlusive events needs to be weighed against any increase in major bleeds. Further trials are in progress.
FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK, and the European Community Biomed Programme.

PMID 19482214  Lancet. 2009 May 30;373(9678):1849-60. doi: 10.1016/S01・・・
著者: CAPRIE Steering Committee
雑誌名: Lancet. 1996 Nov 16;348(9038):1329-39.
Abstract/Text BACKGROUND: Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate.
METHODS: CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years.
FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group.
INTERPRETATION: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin.

PMID 8918275  Lancet. 1996 Nov 16;348(9038):1329-39.

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