今日の臨床サポート

安定狭心症

著者: 吉野秀朗 医療法人財団慈生会 野村病院 病院長/杏林大学医学部循環器内科 客員教授

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

著者校正済:2021/11/24
現在監修レビュー中
参考ガイドライン:
  1. 欧州心臓病学会:2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes
  1. 米国心臓病学会財団ほか:2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease
  1. 米国心臓病学会財団ほか:2014 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Focuses Update of Guideline for the diagnosis and management of patients with stable ischemic heart disease
  1. 日本循環器学会:慢性冠動脈疾患診断ガイドライン(2018年改訂版)
  1. 日本循環器学会/日本心臓血管外科学会:安定冠動脈疾患の血行再建ガイドライン(2018年改訂版)
患者向け説明資料

概要・推奨   

  1. 安定狭心症とは、虚血性心疾患の1つで、臨床経過に基づき分類したもののうち、症状が安定している(発作の発現様式・症状が3週間以上同じ)状態である。
  1. 安定狭心症は、狭心症状の確認、不安定狭心症の除外、労作時の心筋虚血の確認により診断となる。2019年European Society of Cardiology (ESC) ガイドラインでは、6つのカテゴリーを含めて慢性冠動脈症候群 (Chronic coronary syndrome) と名付けている。すなわち、(i)狭心症状の安定している症例(呼吸困難症状の有無に関わらず)、(ii)新規発症の心不全または左室機能低下があり冠動脈疾患が示唆される症例、(iii)急性冠症候群と診断されて一年未満か血行再建を施行した症例で無症状ないし有症状で安定している症例、(iv)最初の診断ないし血行再建術を施行して1年以上経過した無症状ないし有症状で安定している症例、(v)冠攣縮性狭心症ないしmicrovessel anginaと診断された症例、(vi)screeningで初めて虚血性心疾患と診断された症例、である。しかし、(v)は、必ずしも安定狭心症に含めるのが妥当か否か議論のあるところであり、我が国のガイドラインや成書ではこれは安定狭心症には含めていない。(vi)は、精査の後(i)に含まれる症例群かも知れない。2019年ESCガイドラインでは、新たに虚血性の慢性心不全も加えているところがこれまでのガイドラインとは異なる。また、陳旧性心筋梗塞やPCI後の症例も慢性虚血性心疾患として管理すべきであるとしている。「安定狭心症」は、現在、各国のガイドラインで扱っているように「慢性虚血性心疾患」のひとつであるが、単に、「狭心症」という狭い概念でとらえた疾患のみを扱うのではなく、虚血性心疾患という広い概念のなかで、stableかunstableかで分け、いつでも変化増悪しうるリスクを持つstableな虚血性心疾患を扱う。
  1. 狭心症の診断には、問診が最も重要である。狭心症の典型的症状か否か、症状は増悪しているか、安定しているか、冠動脈疾患の危険因子を持つかを確認する。症状が、増悪しているなら「不安定狭心症」「急性冠症候群」を考慮する。不安定狭心症の定義は、1)安静時狭心症(20分以上持続する)、2)発症から2カ月以内の新規発症のCCS ⅡかⅢの狭心症、3)労作性増悪型狭心症。
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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:
吉野秀朗 : 特に申告事項無し[2021年]
監修:代田浩之 : 未申告[2021年]

改訂のポイント:
  1. 「安定狭心症」を最近のガイドラインに沿って、その対象を広く「慢性冠動脈疾患」とした。
  1. 「慢性冠動脈疾患」に、心不全徴候ないしは左室機能低下を伴う症例を含む。
  1. 「慢性冠動脈疾患」に、ACS発症後1年未満、ACS発症後1年以上を分けて、含む。
  1. 「狭心症」という狭い概念でとらえた疾患のみを扱うのではなく、虚血性心疾患という広い概念のなかで、stableかunstableかで分け、いつでも変化増悪しうるリスクを持つstableな虚血性心疾患を扱う。

病態・疫学・診察

疾患情報(疫学・病態)  
  1.  安定狭心症とは、虚血性心疾患の1つで、症状が安定している(発作の発現様式・症状が3週間以上同じ)狭心症のうち、冠攣縮性狭心症を除外した状態である。
  1. 虚血性心疾患とは、虚血性心疾患冠動脈の動脈硬化性変化に伴う狭窄や閉塞による血流障害によって生じる心筋虚血を原因とする疾患を総称していう。また、虚血性心疾患のうち、生じる心筋虚血が一過性である場合を「狭心症」といい、心筋細胞に壊死が生じて一過性でなくなった状態を「心筋梗塞」と呼ぶ。安定狭心症では動脈硬化が進んで冠動脈が徐々に狭くなる病態に対し、不安定狭心症ではプラークが破裂して急速に冠動脈が閉塞する病態であると考えられている。
  1. 欧州心臓病学会は2019年にChronic Coronary syndrome(慢性冠動脈症候群)の診断と治療のガイドラインを発表した。米国から関連学会が合同で2012年11月に「安定虚血性心疾患の診断と治療」に関するガイドラインを発表した。我が国では日本循環器学会が中心となり慢性冠動脈疾患診断ガイドライン(2018年改訂版)が発表された。治療に関しては、日本循環器学会と日本心臓血管外科学会が合同で安定冠動脈疾患の血行再建ガイドライン(2018年改訂版)が発表された。
 
問診・診察のポイント  
問診:
  1. 狭心症の診断には、問診が最も重要である。狭心症の典型的症状か否か、症状は増悪しているか、安定しているか、冠動脈疾患の危険因子を持つかを確認する。症状が、増悪しているなら「不安定狭心症」「急性冠症候群」を考慮する。

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文献 

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: Allen Jeremias, Ajay J Kirtane, Gregg W Stone
雑誌名: J Am Coll Cardiol. 2017 Jun 6;69(22):2748-2758. doi: 10.1016/j.jacc.2017.04.019.
Abstract/Text Fractional flow reserve (FFR) is an invasive procedure used during coronary angiography to determine the functional significance of coronary stenoses. Its use is particularly helpful in intermediate or angiographically ambiguous lesions in the absence of noninvasive functional studies. Randomized clinical trials have reported improved clinical outcomes with the use of FFR to guide coronary revascularization, including a reduction in cardiac death or myocardial infarction, as well as costs, with an FFR-based strategy compared with a conventional angiography-based approach. Current societal guidelines provide a Class II, Level of Evidence: A recommendation to perform FFR in angiographically intermediate stenoses in the absence of stress testing or in the presence of discordant stress test results and angiographic findings. However, despite the relative ease of use of FFR, multiple technical factors can impair its accuracy, and attention to detail is critical when performing the test. This review focuses on the fundamental basics of FFR testing, clinical evidence, and limitations.

Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 28571641  J Am Coll Cardiol. 2017 Jun 6;69(22):2748-2758. doi: 10・・・
著者: Ju-Hyun Chung, Kyung Eun Lee, Chang-Wook Nam, Joon-Hyung Doh, Hyung Il Kim, Soon-Sung Kwon, Eun Bo Shim, Eun-Seok Shin
雑誌名: Am J Cardiol. 2017 Aug 1;120(3):362-368. doi: 10.1016/j.amjcard.2017.04.057. Epub 2017 May 15.
Abstract/Text Coronary computed tomography angiography (CCTA)-derived fractional flow reserve from computed tomography (CT-FFR) may provide better diagnostic performance over CCTA alone, but the complexity of its method limits the use in clinical environment. The aim of the present study is to validate a newly developed vessel-length based computational fluid dynamics scheme for the computation of FFR based on CCTA data, compare them with invasively measured FFR, and evaluate its diagnostic performance with that of CCTA. One hundred seventeen patients from 4 medical institutions who had clinically indicated invasive coronary angiography for suspected coronary artery disease (CAD) were enrolled. Invasive FFR measurement was performed in 218 vessels and these measurements were regarded as the reference standard. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CT-FFR on a per-vessel basis were 85.8%, 86.2%, 85.5%, 79.8%, and 90.3%, respectively, for CT-FFR ≤0.80, and 66.1%, 75.9%, 59.5%, 55.5%, and 78.8%, respectively, for CCTA ≥50%. A higher area under the receiver operating characteristic curve for CT-FFR was observed compared with CCTA (0.93 vs 0.74, p <0.0001). The CT-FFR and FFR correlated well (r = 0.76, p <0.001) with slight underestimation by CT-FFR (0.014 ± 0.077, p = 0.007). With a novel method of vessel-length based computational fluid dynamics scheme, CT-FFR can be performed at a personal computer enhancing its applicability in clinical situation. The diagnostic accuracy of CT-FFR for the detection of functionally significant CAD was good and was superior to that of CCTA within a population of suspected CAD.

Copyright © 2017 Elsevier Inc. All rights reserved.
PMID 28595860  Am J Cardiol. 2017 Aug 1;120(3):362-368. doi: 10.1016/j・・・
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: 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: William E Boden, Robert A O'Rourke, Koon K Teo, Pamela M Hartigan, David J Maron, William J Kostuk, Merril Knudtson, Marcin Dada, Paul Casperson, Crystal L Harris, Bernard R Chaitman, Leslee Shaw, Gilbert Gosselin, Shah Nawaz, Lawrence M Title, Gerald Gau, Alvin S Blaustein, David C Booth, Eric R Bates, John A Spertus, Daniel S Berman, G B John Mancini, William S Weintraub, COURAGE Trial Research Group
雑誌名: N Engl J Med. 2007 Apr 12;356(15):1503-16. doi: 10.1056/NEJMoa070829. Epub 2007 Mar 26.
Abstract/Text BACKGROUND: In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events.
METHODS: We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6).
RESULTS: There were 211 primary events in the PCI group and 202 events in the medical-therapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P=0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P=0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33).
CONCLUSIONS: As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657 [ClinicalTrials.gov].).

Copyright 2007 Massachusetts Medical Society.
PMID 17387127  N Engl J Med. 2007 Apr 12;356(15):1503-16. doi: 10.1056・・・
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: BARI 2D Study Group, Robert L Frye, Phyllis August, Maria Mori Brooks, Regina M Hardison, Sheryl F Kelsey, Joan M MacGregor, Trevor J Orchard, Bernard R Chaitman, Saul M Genuth, Suzanne H Goldberg, Mark A Hlatky, Teresa L Z Jones, Mark E Molitch, Richard W Nesto, Edward Y Sako, Burton E Sobel
雑誌名: N Engl J Med. 2009 Jun 11;360(24):2503-15. doi: 10.1056/NEJMoa0805796. Epub 2009 Jun 7.
Abstract/Text BACKGROUND: Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established.
METHODS: We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention.
RESULTS: At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003).
CONCLUSIONS: Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.)

2009 Massachusetts Medical Society
PMID 19502645  N Engl J Med. 2009 Jun 11;360(24):2503-15. doi: 10.1056・・・
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, Joseph P. Ornato
雑誌名: J Am Coll Cardiol. 2004 Aug 4;44(3):E1-E211. doi: 10.1016/j.jacc.2004.07.014.
Abstract/Text
PMID 15358047  J Am Coll Cardiol. 2004 Aug 4;44(3):E1-E211. doi: 10.10・・・
著者: R van der Does, U Hauf-Zachariou, E Pfarr, W Holtbrügge, S König, M Griffiths, A Lahiri
雑誌名: Am J Cardiol. 1999 Mar 1;83(5):643-9.
Abstract/Text In a double-blind, randomized, 3-month multicenter study, the safety and tolerability and the antianginal and anti-ischemic efficacy of carvedilol 25 to 50 mg twice daily were assessed in comparison with metoprolol 50 to 100 mg twice daily in younger and elderly patients with stable angina. After a 7-day placebo run-in at the end of which a symptom-limited bicycle ergometric exercise was performed, 368 patients were randomly allocated to the parallel treatment groups. After 4 weeks of therapy with a low dose, a further exercise test was performed and patients were titrated in single-blind fashion to the higher dose if the increase in total exercise time was < 1 minute, and there was no safety concern. After a further 8 weeks of treatment a third exercise test was performed. Carvedilol low dose/high dose was shown to be at least as safe and well tolerated as metoprolol low dose/high dose both in younger and elderly patients. There were no hitherto unknown adverse events and no marked change in the types of events after increase of the doses. Early adverse events after treatment initiation or uptitration were equal with both medications, indicating no particular risk associated with carvedilol's vasodilatory action. No rebound phenomena were observed. Both drugs showed good antianginal and anti-ischemic efficacy, with marked increases on uptitration including patients > or = 65 years of age. However, in the doses selected, which appeared equipotent with respect to beta blockade, carvedilol's improvement of time to 1-mm ST-segment depression was statistically significantly greater than that of metoprolol. This could be due to its additional vasodilatory or antioxidative actions. Based on the safety and efficacy data of the present study, use of the higher of the 2 recommended doses of carvedilol and metoprolol appears justified in younger and elderly patients without adequate therapeutic control at lower doses.

PMID 10080412  Am J Cardiol. 1999 Mar 1;83(5):643-9.
著者: R Weiss, D Ferry, E Pickering, L K Smith, G Dennish, S Krug-Gourley, M A Lukas
雑誌名: Am J Cardiol. 1998 Oct 15;82(8):927-31.
Abstract/Text Carvedilol is a nonselective beta-receptor antagonist with vasodilating properties primarily due to selective alpha-1 antagonism. This 4-treatment, 5-period, double-blind, crossover study evaluated the efficacy and safety of 3 doses of carvedilol (12.5, 25, and 50 mg given twice daily) versus placebo in 122 patients with chronic stable angina. Carvedilol in doses of 25 mg twice daily and 50 mg twice daily was statistically superior to placebo with respect to time to angina (placebo: 316 seconds; 25 mg carvedilol: 337 seconds, p = 0.0039; 50 mg: 345 seconds, p <0.0001) and time to 1-mm ST-segment depression (placebo: 301 seconds; 25 mg: 313 seconds; 50 mg: 323 seconds; p <0.0001). The percentage of patients reporting any adverse experience was slightly less in those receiving placebo (placebo: 28.4%; 12.5 mg: 33.1%; 25 mg: 34.5%; 50 mg: 31.9%). Carvedilol is effective and safe in treating patients with chronic stable angina.

PMID 9794346  Am J Cardiol. 1998 Oct 15;82(8):927-31.
著者: J D Parker, J O Parker
雑誌名: N Engl J Med. 1998 Feb 19;338(8):520-31. doi: 10.1056/NEJM199802193380807.
Abstract/Text
PMID 9468470  N Engl J Med. 1998 Feb 19;338(8):520-31. doi: 10.1056/N・・・
著者: C J Pepine, L M Lopez, D M Bell, E M Handberg-Thurmond, R G Marks, S McGorray
雑誌名: J Am Coll Cardiol. 1997 Oct;30(4):955-61.
Abstract/Text OBJECTIVES: We sought to evaluate the effects of intermittent transdermal nitroglycerin (TD-NTG) on the occurrence of ischemia during patch-off hours in patients with stable angina pectoris receiving a beta-adrenergic blocking agent or calcium antagonist, or both.
BACKGROUND: The current recommendations for the use of intermittent TD-NTG may be associated with the occurrence of rebound ischemia.
METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, crossover trial with three study periods. Tolerability to TD-NTG was assessed in Period I. Seventy-two patients were assigned to receive either double-blind transdermal placebo or maximally tolerated TD-NTG for 2 weeks (Period II) and were then crossed over to the alternative treatment for another 2 weeks (Period III). The patients were instructed to apply medication daily at 8 AM, to remove it at 10 PM and to note symptoms and sublingual nitroglycerin (SL-NTG) use in a diary. The occurrence of ischemia was assessed from patient-perceived angina, symptom-limited exercise treadmill test (ETT) and 48-h ambulatory electrocardiographic (AECG) monitoring.
RESULTS: Transdermal NTG (0.2 to 0.4 mg/h) significantly reduced the magnitude of ST segment depression at angina onset during ETT compared with placebo. Total angina frequency was not significantly different between TD-NTG (mean [+/-SD] 3.2 +/- 4.2) and placebo (3.3 +/- 5.2). During patch-off hours, angina frequency increased with TD-NTG (1.1 +/- 2.1) compared with placebo (0.7 +/- 1.6) (p = 0.03). Similar trends for an increase in ischemia after TD-NTG were also observed from AECG analyses. Specifically, ischemia frequency tended to be lower during patch-off hours for placebo than with TD-NTG (0.05 +/- 0.09 vs. 0.08 +/- 0.20 episodes/h, respectively, p = 0.08), even though frequency of ischemia tended to be higher during patch-on hours for placebo than with TD-NTG (0.12 +/- 0.19 vs. 0.07 +/- 0.15 episodes/h, respectively, p = 0.11). During placebo, ischemia frequency decreased 58% (patch-on to patch-off, p = 0.01) compared with a 14% increase with TD-NTG. These changes attenuate the usual circadian variation in ischemia.
CONCLUSIONS: An increase in ischemia frequency during patch-off hours after use of intermittent TD-NTG was perceived by patients, and this subjective finding was supported by a corresponding trend for AECG ischemia to increase during these same hours.

PMID 9316524  J Am Coll Cardiol. 1997 Oct;30(4):955-61.
著者: Andrew Liuni, Mary Clare Luca, Giuseppe Di Stolfo, Amar Uxa, Justin A Mariani, Tommaso Gori, John D Parker
雑誌名: J Am Coll Cardiol. 2011 Jan 4;57(1):93-8. doi: 10.1016/j.jacc.2010.07.037.
Abstract/Text OBJECTIVES: We aimed to assess whether concurrent administration of atorvastatin would modify the development of tolerance and endothelial dysfunction associated with sustained nitroglycerin (GTN) therapy in humans.
BACKGROUND: Animal studies have demonstrated that administration of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors can protect against GTN-induced endothelial dysfunction and tolerance, likely through an antioxidant mechanism.
METHODS: Thirty-six healthy male volunteers were randomized to receive continuous transdermal GTN (0.6 mg/h) and placebo, atorvastatin (80 mg/day) alone, or continuous transdermal GTN (0.6 mg/h) with concurrent atorvastatin (80 mg/day), all for 7 days. On the second visit, forearm blood flow was measured with venous-occlusion strain gauge plethysmography in response to incremental infusions of acetylcholine (7.5, 15, and 30 μg/min). Acetylcholine infusions were coinfused first with saline, and repeated during the coinfusion of vitamin C (24 mg/min). Blood pressure responses to sublingual GTN (400 μg) were assessed on both visits.
RESULTS: Acetylcholine responses in the GTN plus placebo group were significantly attenuated versus those in the GTN plus atorvastatin and atorvastatin groups (p < 0.01). Coinfusion of vitamin C completely restored acetylcholine responses in the GTN plus placebo group (p < 0.01 vs. saline coinfusion), but caused no change in either the atorvastatin or the GTN plus atorvastatin groups. Blood pressure responses to sublingual GTN did not significantly change between visits in subjects receiving GTN plus atorvastatin and atorvastatin alone, but were significantly blunted in the GTN plus placebo group (p < 0.05).
CONCLUSIONS: The present findings demonstrate, for the first time in humans, that atorvastatin prevents both GTN-induced endothelial dysfunction and nitrate tolerance, likely by counteracting the GTN-induced increase in oxidative stress.

Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 21185507  J Am Coll Cardiol. 2011 Jan 4;57(1):93-8. doi: 10.1016/・・・
著者: H Watanabe, M Kakihana, S Ohtsuka, Y Sugishita
雑誌名: J Am Coll Cardiol. 1998 Nov;32(5):1201-6.
Abstract/Text OBJECTIVES: This study was designed to compare the preventive efect of nitrate tolerance between carvedilol with antioxidant properties and arotinolol without antioxidant properties.
BACKGROUND: The attenuation of cyclic guanosine monophosphate (cGMP) production due to inactivation of guanylate cyclase by increased superoxide has been reported as a mechanism of nitrate tolerance. Carvedilol has been known to combine alpha- and beta-blockade with antioxidant properties.
METHODS: To evaluate the preventive effect of nitrate tolerance, 24 patients with untreated hypertension were randomized to receive either carvedilol (10 mg twice a day [carvedilol group, n=8]), arotinolol (10 mg twice a day [arotinolol group, n=8]), or placebo (placebo group, n=8). Vasodilatory response to nitroglycerin (NTG) was assessed with forearm plethysmography by measuring the change in forearm blood flow (FBF) before and 5 min after sublingual administration of 0.3 mg NTG, and at the same time blood samples were taken from veins on the opposite side to measure platelet cGMP. Plethysmography and blood sampling were obtained serially at baseline (day 0), 3 days after carvedilol, arotinolol or placebo administration (day 3) and 3 days after application of a 20 mg/24 h NTG tape concomitantly with carvedilol, arotinolol or placebo (day 6).
RESULTS: There was no significant difference in the response of FBF (%FBF) and cGMP (%cGMP) to sublingual administration of NTG on days 0 and 3 among the three groups. On day 6, %FBF and %cGMP were significantly lower in the arotinolol group and the placebo group than days 0 and 3, but these parameters in the carvedilol group were maintained.
CONCLUSIONS: The results indicated that carvedilol with antioxidant properties may prevent the development of nitrate tolerance during continuous therapy with NTG compared with arotinolol without antioxidant properties.

PMID 9809926  J Am Coll Cardiol. 1998 Nov;32(5):1201-6.
著者: R J Katz, W S Levy, L Buff, A G Wasserman
雑誌名: Circulation. 1991 Apr;83(4):1271-7.
Abstract/Text BACKGROUND: Activation of neurohumoral hormones or sulfhydryl group depletion may contribute to the development of nitroglycerin tolerance. In an attempt to prevent nitrate tolerance, this study evaluated the interaction of nitroglycerin with angiotensin converting enzyme (ACE) inhibitors with and without a sulfhydryl group.
METHODS AND RESULTS: Thirty-four subjects were randomized to a 7-day regimen of enalapril 10 mg b.i.d., captopril 25 mg t.i.d., or placebo. Venodilator response to nitroglycerin was assessed with forearm plethysmography by measuring the change in venous volume after administration of 0.4 mg sublingual nitroglycerin. Plethysmographic measurements were obtained serially 1) at baseline, 2) after 4 days of ACE inhibitor or placebo, 3) 2 hours after application of a 10 mg/24 hr nitroglycerin patch, and 4) 74 hours after continuous nitropatch application. ACE inhibition alone caused no significant change in the response to sublingual nitroglycerin. Nitrate response remained unchanged after 2 hours ("acute") of nitropatch exposure in all three groups. After 74 hours ("chronic") of continuous nitropatch application, the venodilator response to sublingual nitroglycerin was reduced by 40% in the placebo group, 10% in the enalapril group, and 2% in the captopril group. This attenuation was significant only in the placebo group (p less than 0.01). Pairwise comparison of nitrate response between groups was significantly different between the captopril and placebo groups (p less than 0.01) and between the placebo and enalapril groups (p less than 0.05). Plasma renin levels increased equally in the enalapril and captopril groups. Body weight increased only in the placebo group, suggesting prevention of nitrate-induced volume expansion in the ACE inhibitor groups.
CONCLUSIONS: This study demonstrates that ACE inhibitors may prevent nitrate tolerance to long-term nitrate therapy.

PMID 1901528  Circulation. 1991 Apr;83(4):1271-7.
著者: L Pizzulli, A Hagendorff, M Zirbes, W Fehske, S Ewig, W Jung, B Lüderitz
雑誌名: Am Heart J. 1996 Feb;131(2):342-9.
Abstract/Text We investigated whether captopril is able to potentiate vasodilation and prevent tolerance to a 48-hour infusion of nitroglycerin (NTG). Twenty-six patients were randomly assigned to a 7-day regimen of captopril (50 mg/day) or placebo. The hemodynamic response to a 0.8 mg sublingual NTG dose was assessed by measuring mean arterial pressure (MAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), and cardiac output (CO), and calculating systemic (SVR) and pulmonary vascular resistances (PVR). The parameters were obtained serially at baseline and 1 to 10 minutes after the sublingual NTG application (day 1). Then intravenous NTG was started and maintained for 48 hours (1.5 micrograms/kg/min), and the hemodynamic study was repeated (day 3). There was no difference between the captopril and the placebo groups at day 1 (baseline values and response to sublingual NTG). After the 48-hour infusion, there was a complete loss of the NTG effects in the placebo group (day 1 vs day 3: PAP, 20 +/- 5 mm Hg vs 21 +/- 8 mm Hg; MAP, 86 +/- 11 mm Hg vs 90 +/- 9 mm Hg; SVR, 1295 +/- 330 mm Hg vs 1380 +/- 465 dyne.sec.cm-5) whereas there was still evidence of a persistent vasodilation in the captopril group (day 1 vs day 3: PAP, 19 +/- 4 mm Hg vs 13 +/- 4 mm Hg; MAP, 84 +/- 9 mm Hg vs 74 +/- 10 mm Hg; SVR, 1265 +/- 280 mm Hg vs 1140 +/- 425 dyne.sec.cm-5). The response to sublingual NTG on day 3 was markedly attenuated in the placebo group only. We conclude that captopril does not increase the vasodilatory response to nitroglycerin but is able to prevent developing nitrate tolerance in arterial and venous circulation.

PMID 8579031  Am Heart J. 1996 Feb;131(2):342-9.
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: J A Spertus, T Dewhurst, C M Dougherty, P Nichol
雑誌名: Am Heart J. 2001 Apr;141(4):550-8. doi: 10.1067/mhj.2001.112781.
Abstract/Text OBJECTIVE: Our purpose was to test the hypothesis that converting patients with stable angina to long-acting antianginal medications would improve their functional status, symptom control, treatment satisfaction, and quality of life.
METHODS AND RESULTS: A single-blind randomized trial of 100 patients with stable coronary artery disease was performed in the outpatient clinic of a Veterans Affairs Health System. Outpatients with chronic stable angina taking at least 2 antianginal medications were studied. Patients were randomized to one of two treatments: optimal adjustment of their usual antianginal medications or conversion to solely long-acting medications (long-acting diltiazem +/- nitroglycerin patches +/- atenolol) with subsequent optimization. The primary outcome was the 3-month change in Seattle Angina Questionnaire scores. Although no differences in physical limitation scores were noted, patients randomized to receive long-acting medications had improved symptom control (3-month improvement in anginal stability [19.1 vs 5.6, P =.02] and anginal frequency [17.8 vs 5.5, P =.006]), more treatment satisfaction (3-month improvement of 8.2 vs 3.0, P =.057), and better quality of life (3-month improvement of 11.2 vs 5.6, P =.09) compared with patients whose pretrial medications were optimized. The improvement in symptom control was statistically significant.
CONCLUSION: Converting patients with chronic, stable angina to long-acting antianginal medications resulted in substantial improvements in symptom control with a trend toward better treatment satisfaction and quality of life.

PMID 11275919  Am Heart J. 2001 Apr;141(4):550-8. doi: 10.1067/mhj.200・・・
著者: IONA Study Group
雑誌名: Lancet. 2002 Apr 13;359(9314):1269-75. doi: 10.1016/S0140-6736(02)08265-X.
Abstract/Text BACKGROUND: In addition to its anti-ischaemic effects, the antianginal drug nicorandil is thought to have cardioprotective properties. We did a randomised trial to find out whether nicorandil could reduce the frequency of coronary events in men and women with stable angina and additional risk factors.
METHODS: 5126 patients were randomly assigned 20 mg nicorandil twice daily (n=2565) or identical placebo (n=2561) in addition to standard antianginal therapy. The primary composite endpoint was coronary heart disease death, non-fatal myocardial infarction, or unplanned hospital admission for cardiac chest pain. The secondary endpoint was the combined outcome of coronary heart disease death or non-fatal myocardial infarction. Other outcomes reported include all-cause mortality, all cardiovascular events, and acute coronary syndromes. Mean follow-up was 1.6 years (SD 0.5). Analysis was by intention to treat.
FINDINGS: There were 398 (15.5%) primary endpoint events in the placebo group and 337 (13.1%) in the nicorandil group (hazard ratio 0.83, 95% CI 0.72-0.97; p=0.014). The frequency of the secondary endpoint was not significantly different between the groups (134 events [5.2%] vs 107 events [4.2%]; 0.79, 0.61-1.02; p=0.068). The rate of acute coronary syndromes was 195 (7.6%) in the placebo group and 156 (6.1%) in the nicorandil group (0.79, 0.64-0.98; p=0.028), and the corresponding rates for all cardiovascular events were 436 (17.0%) and 378 (14.7%; 0.86, 0.75-0.98; p=0.027).
INTERPRETATION: We showed a significant improvement in outcome due to a reduction in major coronary events by antianginal therapy with nicorandil in patients with stable angina.

PMID 11965271  Lancet. 2002 Apr 13;359(9314):1269-75. doi: 10.1016/S01・・・
著者: P A Heidenreich, K M McDonald, T Hastie, B Fadel, V Hagan, B K Lee, M A Hlatky
雑誌名: JAMA. 1999 May 26;281(20):1927-36.
Abstract/Text CONTEXT: Which drug is most effective as a first-line treatment for stable angina is not known.
OBJECTIVE: To compare the relative efficacy and tolerability of treatment with beta-blockers, calcium antagonists, and long-acting nitrates for patients who have stable angina.
DATA SOURCES: We identified English-language studies published between 1966 and 1997 by searching the MEDLINE and EMBASE databases and reviewing the bibliographies of identified articles to locate additional relevant studies.
STUDY SELECTION: Randomized or crossover studies comparing antianginal drugs from 2 or 3 different classes (beta-blockers, calcium antagonists, and long-acting nitrates) lasting at least 1 week were reviewed. Studies were selected if they reported at least 1 of the following outcomes: cardiac death, myocardial infarction, study withdrawal due to adverse events, angina frequency, nitroglycerin use, or exercise duration. Ninety (63%) of 143 identified studies met the inclusion criteria.
DATA EXTRACTION: Two independent reviewers extracted data from selected articles, settling any differences by consensus. Outcome data were extracted a third time by 1 of the investigators. We combined results using odds ratios (ORs) for discrete data and mean differences for continuous data. Studies of calcium antagonists were grouped by duration and type of drug (nifedipine vs nonnifedipine).
DATA SYNTHESIS: Rates of cardiac death and myocardial infarction were not significantly different for treatment with beta-blockers vs calcium antagonists (OR, 0.97; 95% confidence interval [CI], 0.67-1.38; P = .79). There were 0.31 (95% CI, 0.00-0.62; P = .05) fewer episodes of angina per week with beta-blockers than with calcium antagonists. beta-Blockers were discontinued because of adverse events less often than were calcium antagonists (OR, 0.72; 95% CI, 0.60-0.86; P<.001). The differences between beta-blockers and calcium antagonists were most striking for nifedipine (OR for adverse events with beta-blockers vs nifedipine, 0.60; 95% CI, 0.47-0.77). Too few trials compared nitrates with calcium antagonists or beta-blockers to draw firm conclusions about relative efficacy.
CONCLUSIONS: beta-Blockers provide similar clinical outcomes and are associated with fewer adverse events than calcium antagonists in randomized trials of patients who have stable angina.

PMID 10349897  JAMA. 1999 May 26;281(20):1927-36.
著者: Antithrombotic Trialists' Collaboration
雑誌名: BMJ. 2002 Jan 12;324(7329):71-86.
Abstract/Text OBJECTIVE: To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.
DESIGN: Collaborative meta-analyses (systematic overviews).
INCLUSION CRITERIA: Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen.
STUDIES REVIEWED: 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens.
MAIN OUTCOME MEASURE: "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death.
RESULTS: Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000.
CONCLUSIONS: Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

PMID 11786451  BMJ. 2002 Jan 12;324(7329):71-86.
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: Enrique P Gurfinkel, Ricardo Leon de la Fuente, Oscar Mendiz, Branco Mautner
雑誌名: Eur Heart J. 2004 Jan;25(1):25-31.
Abstract/Text AIMS: We have previously reported a significant benefit of vaccination against flu on the incidence of a single and composite end-point of death, myocardial infarction or recurrent ischaemia in patients with myocardial necrosis and planned percutaneous coronary interventions. To determine whether the observed benefits of vaccination against flu were maintained beyond the winter season a 1-year follow-up was conducted.
METHODS AND RESULTS: During the winter season, we enrolled prospectively 200 myocardial infarction patients admitted in the first 72 h, and 101 planned angioplasty/stent patients (PCI) without unstable coronary artery disease, prior by-pass surgery, angioplasty or tissue necrosis. Only four patients failed to meet the inclusion criteria. Participants were randomly allocated to receive flu vaccination or remain unvaccinated on top of standard medication (control group). The study was conducted in hospitalized patients with the aim to test the potential beneficial effect of flu vaccination in a secondary prevention scenario. Under intention to treat analysis the incidence of the primary end-point cardiovascular death at 1 year was significantly lower among patients receiving vaccination, 6% as compared with controls, 17% (relative risk with vaccine as compared with controls, 0.34; 95% confidence interval (CI), 0.17 to 0.71; P=0.002). The triple composite end-point occurred in 22% of the patients in the vaccine group vs 37% in controls, hazard ratio 0.59, 95% CI 0.4 to 0.86) P=0.004. The beneficial effect was mainly detected in acute myocardial infarction patients (four events in the active arm vs 21 in the control group, P=0.0002 [95% CI 0.19, 0.07-0.53]), and Cox regression analyses revealed that there was a greater benefit with flu vaccination in patients at high risk according with the TIMI score, and those with non-ST-segment deviation myocardial infarction (95% CI: 0.13 [0.03-0.52])
CONCLUSIONS: Influenza vaccination may reduce the risk of death and ischaemic events in patients suffering from infarction and post-angioplasty during flu season. This effect was significantly evident at 1-year follow-up. Larger confirmatory studies are needed to evaluate the real impact on flu vaccination on outcome after acute coronary syndromes.

PMID 14683739  Eur Heart J. 2004 Jan;25(1):25-31.
著者: M Naghavi, Z Barlas, S Siadaty, S Naguib, M Madjid, W Casscells
雑誌名: Circulation. 2000 Dec 19;102(25):3039-45.
Abstract/Text BACKGROUND: Numerous studies have suggested that microbial agents may promote atherosclerosis. A smaller body of research has suggested that acute respiratory infection may be a risk factor for myocardial infarction (MI). We hypothesized that influenza vaccine might reduce the risk of recurrent MI in patients with documented coronary heart disease (CHD).
METHODS AND RESULTS: A case-control study was performed on 218 CHD patients seen at Memorial Hermann Hospital during the influenza season of October 1997 through March 1998. Patients who experienced new MI were included in the case group, and those who did not experience new MI or unstable angina were assigned to the control group. Data were collected by structured review of patients' charts and through a subsequent telephone survey. Adjusted for history of influenza vaccination in previous years, multivariate logistic regression revealed risk of MI to be associated with current hypertension (OR 4.96, 95% CI 2.06 to 11.96, P<0.0001), hypercholesterolemia (OR 4.08, 95% CI 1.67 to 9.99, P=0.002), smoking (OR 3.75, 95% CI 1.76 to 7.98, P=0.001), and influenza vaccination (OR 0.33, 95% CI 0.13 to 0.82, P=0.017). Despite significant association in univariate analysis, multivitamin therapy and physical exercise were not associated with risk of reinfarction in multivariate analysis.
CONCLUSIONS: In this study in patients with chronic CHD, vaccination against influenza was negatively associated with the development of new MI during the same influenza season. However, to address causal inference, examination of prospective data sets will be needed.

PMID 11120692  Circulation. 2000 Dec 19;102(25):3039-45.
著者: Arintaya Phrommintikul, Srun Kuanprasert, Wanwarang Wongcharoen, Rungsrit Kanjanavanit, Romanee Chaiwarith, Apichard Sukonthasarn
雑誌名: Eur Heart J. 2011 Jul;32(14):1730-5. doi: 10.1093/eurheartj/ehr004. Epub 2011 Feb 2.
Abstract/Text AIMS: Influenza infection has been shown to accentuate the progression of atherosclerosis and precipitate the occurrence of acute coronary syndrome (ACS). However, the protective effects of the influenza vaccine on cardiovascular events are still inconclusive.
METHODS AND RESULTS: The study was a prospective randomized open with blinded endpoint (PROBE) study. The 439 patients who had been admitted due to ACS within 8 weeks were enrolled and randomly allocated to receive inactivated influenza vaccine in the vaccine group and no treatment in the control group. All patients were treated with the standard therapy including revascularization according to primary cardiologists. The primary endpoint, which was the combined major cardiovascular events, including death, hospitalization from ACS, hospitalization from heart failure, and hospitalization from stroke, occurred less frequently in the vaccine group than the control group [9.5 vs. 19.3%, unadjusted HR 0.70 (0.57-0.86), P = 0.004]. There was no significant difference in the incidence of cardiovascular death between the vaccine and control groups [2.3 vs. 5.5%, unadjusted HR 0.39 (0.14-1.12), P = 0.088].
CONCLUSION: The influenza vaccine reduced major cardiovascular events in patients with ACS. Therefore, it should be encouraged as a secondary prevention in this group of patients.

PMID 21289042  Eur Heart J. 2011 Jul;32(14):1730-5. doi: 10.1093/eurhe・・・
著者: Jacob A Udell, Rami Zawi, Deepak L Bhatt, Maryam Keshtkar-Jahromi, Fiona Gaughran, Arintaya Phrommintikul, Andrzej Ciszewski, Hossein Vakili, Elaine B Hoffman, Michael E Farkouh, Christopher P Cannon
雑誌名: JAMA. 2013 Oct 23;310(16):1711-20. doi: 10.1001/jama.2013.279206.
Abstract/Text IMPORTANCE: Among nontraditional cardiovascular risk factors, recent influenzalike infection is associated with fatal and nonfatal atherothrombotic events.
OBJECTIVES: To determine if influenza vaccination is associated with prevention of cardiovascular events.
DATA SOURCES AND STUDY SELECTION: A systematic review and meta-analysis of MEDLINE (1946-August 2013), EMBASE (1947-August 2013), and the Cochrane Library Central Register of Controlled Trials (inception-August 2013) for randomized clinical trials (RCTs) comparing influenza vaccine vs placebo or control in patients at high risk of cardiovascular disease, reporting cardiovascular outcomes either as efficacy or safety events.
DATA EXTRACTION AND SYNTHESIS: Two investigators extracted data independently on trial design, baseline characteristics, outcomes, and safety events from published manuscripts and unpublished supplemental data. High-quality studies were considered those that described an appropriate method of randomization, allocation concealment, blinding, and completeness of follow-up.
MAIN OUTCOMES AND MEASURES: Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for composite cardiovascular events, cardiovascular mortality, all-cause mortality, and individual cardiovascular events. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization.
RESULTS: Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data.
CONCLUSIONS AND RELEVANCE: In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.

PMID 24150467  JAMA. 2013 Oct 23;310(16):1711-20. doi: 10.1001/jama.20・・・
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: 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: Arie Pieter Kappetein, Ted E Feldman, Michael J Mack, Marie-Claude Morice, David R Holmes, Elisabeth Ståhle, Keith D Dawkins, Friedrich W Mohr, Patrick W Serruys, Antonio Colombo
雑誌名: Eur Heart J. 2011 Sep;32(17):2125-34. doi: 10.1093/eurheartj/ehr213. Epub 2011 Jun 22.
Abstract/Text AIMS: Long-term randomized comparisons of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in left main coronary (LM) disease and/or three-vessel disease (3VD) patients have been limited. This analysis compares 3-year outcomes in LM and/or 3VD patients treated with CABG or PCI with TAXUS Express stents.
METHODS AND RESULTS: SYNTAX is an 85-centre randomized clinical trial (n= 1800). Prospectively screened, consecutive LM and/or 3VD patients were randomized if amenable to equivalent revascularization using either technique; if not, they were entered into a registry. Patients in the randomized cohort will continue to be followed for 5 years. At 3 years, major adverse cardiac and cerebrovascular events [MACCE: death, stroke, myocardial infarction (MI), and repeat revascularization; CABG 20.2% vs. PCI 28.0%, P< 0.001], repeat revascularization (10.7 vs. 19.7%, P< 0.001), and MI (3.6 vs. 7.1%, P= 0.002) were elevated in the PCI arm. Rates of the composite safety endpoint (death/stroke/MI 12.0 vs. 14.1%, P= 0.21) and stroke alone (3.4 vs. 2.0%, P= 0.07) were not significantly different between treatment groups. Major adverse cardiac and cerebrovascular event rates were not significantly different between arms in the LM subgroup (22.3 vs. 26.8%, P= 0.20) but were higher with PCI in the 3VD subgroup (18.8 vs. 28.8%, P< 0.001).
CONCLUSIONS: At 3 years, MACCE was significantly higher in PCI- compared with CABG-treated patients. In patients with less complex disease (low SYNTAX scores for 3VD or low/intermediate terciles for LM patients), PCI is an acceptable revascularization, although longer follow-up is needed to evaluate these two revascularization strategies.

PMID 21697170  Eur Heart J. 2011 Sep;32(17):2125-34. doi: 10.1093/eurh・・・
著者: Michael E Farkouh, Michael Domanski, Lynn A Sleeper, Flora S Siami, George Dangas, Michael Mack, May Yang, David J Cohen, Yves Rosenberg, Scott D Solomon, Akshay S Desai, Bernard J Gersh, Elizabeth A Magnuson, Alexandra Lansky, Robin Boineau, Jesse Weinberger, Krishnan Ramanathan, J Eduardo Sousa, Jamie Rankin, Balram Bhargava, John Buse, Whady Hueb, Craig R Smith, Victoria Muratov, Sameer Bansilal, Spencer King, Michel Bertrand, Valentin Fuster, FREEDOM Trial Investigators
雑誌名: N Engl J Med. 2012 Dec 20;367(25):2375-84. doi: 10.1056/NEJMoa1211585. Epub 2012 Nov 4.
Abstract/Text BACKGROUND: In some randomized trials comparing revascularization strategies for patients with diabetes, coronary-artery bypass grafting (CABG) has had a better outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease.
METHODS: In this randomized trial, we assigned patients with diabetes and multivessel coronary artery disease to undergo either PCI with drug-eluting stents or CABG. The patients were followed for a minimum of 2 years (median among survivors, 3.8 years). All patients were prescribed currently recommended medical therapies for the control of low-density lipoprotein cholesterol, systolic blood pressure, and glycated hemoglobin. The primary outcome measure was a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke.
RESULTS: From 2005 through 2010, we enrolled 1900 patients at 140 international centers. The patients' mean age was 63.1±9.1 years, 29% were women, and 83% had three-vessel disease. The primary outcome occurred more frequently in the PCI group (P=0.005), with 5-year rates of 26.6% in the PCI group and 18.7% in the CABG group. The benefit of CABG was driven by differences in rates of both myocardial infarction (P<0.001) and death from any cause (P=0.049). Stroke was more frequent in the CABG group, with 5-year rates of 2.4% in the PCI group and 5.2% in the CABG group (P=0.03).
CONCLUSIONS: For patients with diabetes and advanced coronary artery disease, CABG was superior to PCI in that it significantly reduced rates of death and myocardial infarction, with a higher rate of stroke. (Funded by the National Heart, Lung, and Blood Institute and others; FREEDOM ClinicalTrials.gov number, NCT00086450.).

PMID 23121323  N Engl J Med. 2012 Dec 20;367(25):2375-84. doi: 10.1056・・・
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: Mark A Hlatky, Derek B Boothroyd, Dena M Bravata, Eric Boersma, Jean Booth, Maria M Brooks, Didier Carrié, Tim C Clayton, Nicolas Danchin, Marcus Flather, Christian W Hamm, Whady A Hueb, Jan Kähler, Sheryl F Kelsey, Spencer B King, Andrzej S Kosinski, Neuza Lopes, Kathryn M McDonald, Alfredo Rodriguez, Patrick Serruys, Ulrich Sigwart, Rodney H Stables, Douglas K Owens, Stuart J Pocock
雑誌名: Lancet. 2009 Apr 4;373(9670):1190-7. doi: 10.1016/S0140-6736(09)60552-3. Epub 2009 Mar 19.
Abstract/Text BACKGROUND: Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are alternative treatments for multivessel coronary disease. Although the procedures have been compared in several randomised trials, their long-term effects on mortality in key clinical subgroups are uncertain. We undertook a collaborative analysis of data from randomised trials to assess whether the effects of the procedures on mortality are modified by patient characteristics.
METHODS: We pooled individual patient data from ten randomised trials to compare the effectiveness of CABG with PCI according to patients' baseline clinical characteristics. We used stratified, random effects Cox proportional hazards models to test the effect on all-cause mortality of randomised treatment assignment and its interaction with clinical characteristics. All analyses were by intention to treat.
FINDINGS: Ten participating trials provided data on 7812 patients. PCI was done with balloon angioplasty in six trials and with bare-metal stents in four trials. Over a median follow-up of 5.9 years (IQR 5.0-10.0), 575 (15%) of 3889 patients assigned to CABG died compared with 628 (16%) of 3923 patients assigned to PCI (hazard ratio [HR] 0.91, 95% CI 0.82-1.02; p=0.12). In patients with diabetes (CABG, n=615; PCI, n=618), mortality was substantially lower in the CABG group than in the PCI group (HR 0.70, 0.56-0.87); however, mortality was similar between groups in patients without diabetes (HR 0.98, 0.86-1.12; p=0.014 for interaction). Patient age modified the effect of treatment on mortality, with hazard ratios of 1.25 (0.94-1.66) in patients younger than 55 years, 0.90 (0.75-1.09) in patients aged 55-64 years, and 0.82 (0.70-0.97) in patients 65 years and older (p=0.002 for interaction). Treatment effect was not modified by the number of diseased vessels or other baseline characteristics.
INTERPRETATION: Long-term mortality is similar after CABG and PCI in most patient subgroups with multivessel coronary artery disease, so choice of treatment should depend on patient preferences for other outcomes. CABG might be a better option for patients with diabetes and patients aged 65 years or older because we found mortality to be lower in these subgroups.

PMID 19303634  Lancet. 2009 Apr 4;373(9670):1190-7. doi: 10.1016/S0140・・・
著者: Subodh Verma, Michael E Farkouh, Bobby Yanagawa, David H Fitchett, Muhammad R Ahsan, Marc Ruel, Sachin Sud, Milan Gupta, Shantanu Singh, Nandini Gupta, Asim N Cheema, Lawrence A Leiter, Paul W M Fedak, Hwee Teoh, David A Latter, Valentin Fuster, Jan O Friedrich
雑誌名: Lancet Diabetes Endocrinol. 2013 Dec;1(4):317-28. doi: 10.1016/S2213-8587(13)70089-5. Epub 2013 Sep 13.
Abstract/Text BACKGROUND: The choice between coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) for revascularisation in patients with diabetes and multivessel coronary artery disease, who account for 25% of revascularisation procedures, is much debated. We aimed to assess whether all-cause mortality differed between patients with diabetes who had CABG or PCI by doing a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing CABG with PCI in the modern stent era.
METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from Jan 1, 1980, to March 12, 2013, for studies reported in English. Eligible studies were those in which investigators enrolled adult patients with diabetes and multivessel coronary artery disease, randomised them to CABG (with arterial conduits in at least 80% of participants) or PCI (with stents in at least 80% of participants), and reported outcomes separately in patients with diabetes, with a minimum of 12 months of follow-up. We used random-effects models to calculate risk ratios (RR) and 95% CIs for pooled data. We assessed heterogeneity using I(2). The primary outcome was all-cause mortality in patients with diabetes who had CABG compared with those who had PCI at 5-year (or longest) follow-up.
FINDINGS: The initial search strategy identified 3414 citations, of which eight trials were eligible. These eight trials included 7468 participants, of whom 3612 had diabetes. Four of the RCTs used bare metal stents (BMS; ERACI II, ARTS, SoS, MASS II) and four used drug-eluting stents (DES; FREEDOM, SYNTAX, VA CARDS, CARDia). At mean or median 5-year (or longest) follow-up, individuals with diabetes allocated to CABG had lower all-cause mortality than did those allocated to PCI (RR 0.67, 95% CI 0.52-0.86; p=0.002; I(2)=25%; 3131 patients, eight trials). Treatment effects in individuals without diabetes showed no mortality benefit (1.03, 0.77-1.37; p=0.78; I(2)=46%; 3790 patients, five trials; p interaction=0.03). We identified no differences in outcome whether PCI was done with BMS or DES. When present, we identified no clear causes of heterogeneity.
INTERPRETATION: In the modern era of stenting and optimum medical therapy, revascularisation of patients with diabetes and multivessel disease by CABG decreases long-term mortality by about a third compared with PCI using either BMS or DES. CABG should be strongly considered for these patients.

Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID 24622417  Lancet Diabetes Endocrinol. 2013 Dec;1(4):317-28. doi: ・・・
著者: Vasim Farooq, David van Klaveren, Ewout W Steyerberg, Emanuele Meliga, Yvonne Vergouwe, Alaide Chieffo, Arie Pieter Kappetein, Antonio Colombo, David R Holmes, Michael Mack, Ted Feldman, Marie-Claude Morice, Elisabeth Ståhle, Yoshinobu Onuma, Marie-angèle Morel, Hector M Garcia-Garcia, Gerrit Anne van Es, Keith D Dawkins, Friedrich W Mohr, Patrick W Serruys
雑誌名: Lancet. 2013 Feb 23;381(9867):639-50. doi: 10.1016/S0140-6736(13)60108-7.
Abstract/Text BACKGROUND: The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations.
METHODS: SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score ≥33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972.
FINDINGS: SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (p(interaction) 0·0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (p(interaction) 0·67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0·725 and for external (DELTA registry) validation of 0·716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0·567 and 0·612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI.
INTERPRETATION: Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score.
FUNDING: Boston Scientific Corporation.

Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID 23439103  Lancet. 2013 Feb 23;381(9867):639-50. doi: 10.1016/S014・・・
著者: Tara I Chang, David Shilane, Dhruv S Kazi, Maria E Montez-Rath, Mark A Hlatky, Wolfgang C Winkelmayer
雑誌名: J Am Soc Nephrol. 2012 Dec;23(12):2042-9. doi: 10.1681/ASN.2012060554.
Abstract/Text Thirty to sixty percent of patients with ESRD on dialysis have coronary heart disease, but the optimal strategy for coronary revascularization is unknown. We used data from the United States Renal Data System to define a cohort of 21,981 patients on maintenance dialysis who received initial coronary revascularization with either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) between 1997 and 2009 and had at least 6 months of prior Medicare coverage as their primary payer. The primary outcome was death from any cause, and the secondary outcome was a composite of death or myocardial infarction. Overall survival rates were consistently poor during the study period, with unadjusted 5-year survival rates of 22%-25% irrespective of revascularization strategy. Using multivariable-adjusted proportional hazards regression, we found that CABG compared with PCI associated with significantly lower risks for both death (HR=0.87, 95% CI=0.84-0.90) and the composite of death or myocardial infarction (HR=0.88, 95% CI=0.86-0.91). Results were similar in analyses using a propensity score-matched cohort. In the absence of data from randomized trials, these results suggest that CABG may be preferred over PCI for multivessel coronary revascularization in appropriately selected patients on maintenance dialysis.

PMID 23204445  J Am Soc Nephrol. 2012 Dec;23(12):2042-9. doi: 10.1681/・・・
著者: Caroline S Fox, Paul Muntner, Anita Y Chen, Karen P Alexander, Matthew T Roe, Christopher P Cannon, Jorge F Saucedo, Michael C Kontos, Stephen D Wiviott, Acute Coronary Treatment and Intervention Outcomes Network registry
雑誌名: Circulation. 2010 Jan 26;121(3):357-65. doi: 10.1161/CIRCULATIONAHA.109.865352. Epub 2010 Jan 11.
Abstract/Text BACKGROUND: Chronic kidney disease (CKD) is a risk factor for myocardial infarction (MI) and death. Our goal was to characterize the association between CKD severity and short-term outcomes and the use of in-hospital evidence-based therapies among patients with ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI).
METHODS AND RESULTS: The study sample was drawn from the Acute Coronary Treatment and Intervention Outcomes Network registry, a nationwide sample of STEMI (n=19 029) and NSTEMI (n=30 462) patients. Estimated glomerular filtration rate was calculated with the Modification of Diet in Renal Disease equation in relation to use of immediate (first 24 hours) therapies and early (first 48 hours) cardiac catheterization as well as in-hospital major bleeding events and death. Overall, 30.5% and 42.9% of patients with STEMI and NSTEMI, respectively, had CKD. Regardless of MI type, patients with progressively more severe CKD had higher rates of death. For STEMI, the odds ratio for stage 3a, 3b, 4, and 5 CKD compared with patients with no CKD was 2.49, 3.72, 4.82, and 7.97, respectively (P(trend)<0.0001). For NSTEMI, the analogous odds ratios were 1.81, 2.41, 3.50, and 4.09 (P for trend <0.0001). In addition, patients with progressively more severe CKD were less likely to receive immediate evidence-based therapies including aspirin, beta-blockers, or clopidogrel, were less likely to undergo any reperfusion (STEMI) or revascularization (NSTEMI), and had higher rates of bleeding.
CONCLUSIONS: Reports over the past decade have highlighted the importance of CKD among patients with MI. Data from this contemporary cohort suggest that patients with CKD still receive fewer evidence-based therapies and have substantially higher mortality rates.

PMID 20065168  Circulation. 2010 Jan 26;121(3):357-65. doi: 10.1161/CI・・・
著者: Li-qiu Yan, Li-jun Guo, Fu-chun Zhang, Wei Gao
雑誌名: Can J Cardiol. 2011 Nov-Dec;27(6):768-72. doi: 10.1016/j.cjca.2011.04.004. Epub 2011 Jul 24.
Abstract/Text BACKGROUND: Chronic kidney disease (CKD) is highly prevalent in patients with coronary artery disease (CAD) and is an independent risk factor for adverse cardiovascular disease (CVD) and all-cause mortality in patients with acute coronary syndromes. SYNTAX score (SXscore) can predict the outcomes of patients undergoing percutaneous coronary intervention. However, the association between kidney function and SXscore has not been previously reported.
METHODS: The estimated glomerular filtration rate (eGFR) and SXscore were retrospectively collected in 2262 patients with established CAD undergoing coronary angiography at Peking University Third Hospital from March 2005 to September 2010. Ordinal logistic regression and Pearson and partial correlation were used to analyze the association between eGFR and SXscore.
RESULTS: Patients with renal dysfunction were older, more likely to be female, and have a history of hypertension and diabetes. The unadjusted correlation coefficient of eGFR and SXscore was -0.125 (P<0.001).This remained significant after adjustment for age, sex, hypertension, diabetes, hyperlipidemia, or current smoking (r=-0.075, P=0.019). Ordinal logistic regression showed that age, gender, diabetes, and eGFR exerted independent influences on SXscore.
CONCLUSIONS: Kidney function was an independent predictor of SXscore in patients with established CAD. This helps explain the increased risk of cardiovascular disease events and mortality in patients with renal dysfunction. Further prospective multicentre studies are needed to confirm this finding.

Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
PMID 21791364  Can J Cardiol. 2011 Nov-Dec;27(6):768-72. doi: 10.1016/・・・
著者: Hui Zheng, Song Xue, Feng Lian, Ri-Tai Huang, Zhen-Lei Hu, Yong-Yi Wang
雑誌名: Eur J Cardiothorac Surg. 2013 Mar;43(3):459-67. doi: 10.1093/ejcts/ezs360. Epub 2012 Jul 9.
Abstract/Text End-stage renal disease (ESRD) patients are at high risk for coronary artery disease (CAD). The optimal revascularization strategy remains unknown. We performed a meta-analysis of retrospective observational trials to compare coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for ESRD patients with CAD. A search of published reports was conducted to identify clinical studies comparing CABG with PCI in ESRD patients with CAD with a minimal follow-up of 12 months. Sixteen studies included 32 350 ESRD patients with revascularization. Compared with PCI, CABG was associated with a lower risk for late mortality [relative risk (RR) 0.90, 95% confidence interval (CI) 0.87-0.93], myocardial infarction event (RR 0.64, 95% CI: 0.61-0.68), repeat revascularization event (RR 0.22, 95% CI: 0.16-0.31) and cumulative events (RR 0.69, 95% CI: 0.65-0.73), despite having a higher risk for early mortality (RR 1.98, 95% CI: 1.51-2.60). In conclusion, the long-term results of PCI in ESRD patients are dismal, and CABG is significantly superior to PCI in this subset of patients.

PMID 22778175  Eur J Cardiothorac Surg. 2013 Mar;43(3):459-67. doi: 10・・・
著者: Eric J Velazquez, Kerry L Lee, Marek A Deja, Anil Jain, George Sopko, Andrey Marchenko, Imtiaz S Ali, Gerald Pohost, Sinisa Gradinac, William T Abraham, Michael Yii, Dorairaj Prabhakaran, Hanna Szwed, Paolo Ferrazzi, Mark C Petrie, Christopher M O'Connor, Pradit Panchavinnin, Lilin She, Robert O Bonow, Gena Roush Rankin, Robert H Jones, Jean-Lucien Rouleau, STICH Investigators
雑誌名: N Engl J Med. 2011 Apr 28;364(17):1607-16. doi: 10.1056/NEJMoa1100356. Epub 2011 Apr 4.
Abstract/Text BACKGROUND: The role of coronary-artery bypass grafting (CABG) in the treatment of patients with coronary artery disease and heart failure has not been clearly established.
METHODS: Between July 2002 and May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes.
RESULTS: The primary outcome occurred in 244 patients (41%) in the medical-therapy group and 218 (36%) in the CABG group (hazard ratio with CABG, 0.86; 95% confidence interval [CI], 0.72 to 1.04; P=0.12). A total of 201 patients (33%) in the medical-therapy group and 168 (28%) in the CABG group died from an adjudicated cardiovascular cause (hazard ratio with CABG, 0.81; 95% CI, 0.66 to 1.00; P=0.05). Death from any cause or hospitalization for cardiovascular causes occurred in 411 patients (68%) in the medical-therapy group and 351 (58%) in the CABG group (hazard ratio with CABG, 0.74; 95% CI, 0.64 to 0.85; P<0.001). By the end of the follow-up period (median, 56 months), 100 patients in the medical-therapy group (17%) underwent CABG, and 555 patients in the CABG group (91%) underwent CABG.
CONCLUSIONS: In this randomized trial, there was no significant difference between medical therapy alone and medical therapy plus CABG with respect to the primary end point of death from any cause. Patients assigned to CABG, as compared with those assigned to medical therapy alone, had lower rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes. (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories; STICH ClinicalTrials.gov number, NCT00023595.).

PMID 21463150  N Engl J Med. 2011 Apr 28;364(17):1607-16. doi: 10.1056・・・
著者: Eric J Velazquez, Judson B Williams, Eric Yow, Linda K Shaw, Kerry L Lee, Harry R Phillips, Christopher M O'Connor, Peter K Smith, Robert H Jones
雑誌名: Ann Thorac Surg. 2012 Feb;93(2):523-30. doi: 10.1016/j.athoracsur.2011.10.064.
Abstract/Text BACKGROUND: We prospectively applied the Surgical Treatment of Ischemic Cardiomyopathy trial entry criteria to an observational database to determine whether coronary artery bypass grafting (CABG) decreases mortality compared with medical therapy (MED) for patients with coronary artery disease and depressed left ventricular ejection fraction.
METHODS: This was a retrospective, observational, cohort study of prospectively collected data from the Duke Databank for Cardiovascular Disease. Long-term mortality was the main outcome measure. Between January 1, 1995, and July 31, 2009, 86,874 patients underwent cardiac catheterization for suspected ischemic heart disease and were evaluated for inclusion in the analysis.
RESULTS: A total of 2,624 patients were found to have left ventricular ejection fraction less than 0.35, coronary artery disease amenable to CABG, and no left main stenosis of greater than 50%. After exclusions including ongoing Canadian Cardiovascular Society class III angina and acute myocardial infarction, 763 patients were included for propensity score analysis, including 624 who received MED and 139 who underwent CABG. Adjusted mortality curves were constructed for those patients in the three quintiles most likely to receive CABG. The curves diverged early, with risk-adjusted mortality rates at 5 years of 46% for MED versus 29% for CABG, and the survival benefit of CABG over MED continued through 10 years of follow-up (hazard ratio, 0.63; 95% confidence interval, 0.45 to 0.88).
CONCLUSIONS: Among a propensity-matched, risk-adjusted, observational cohort of patients with coronary artery disease, left ventricular ejection fraction less than 0.35, and no left main disease of greater than 50%, CABG is associated with a survival advantage over MED through 10 years of follow-up.

Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
PMID 22269720  Ann Thorac Surg. 2012 Feb;93(2):523-30. doi: 10.1016/j.・・・
著者: Jung-Min Ahn, Jae-Hyung Roh, Young-Hak Kim, Duk-Woo Park, Sung-Cheol Yun, Pil Hyung Lee, Mineok Chang, Hyun Woo Park, Seung-Whan Lee, Cheol Whan Lee, Seong-Wook Park, Suk Jung Choo, CheolHyun Chung, JaeWon Lee, Do-Sun Lim, Seung-Woon Rha, Sang-Gon Lee, Hyeon-Cheol Gwon, Hyo-Soo Kim, In-Ho Chae, Yangsoo Jang, Myung-Ho Jeong, Seung-Jea Tahk, Ki Bae Seung, Seung-Jung Park
雑誌名: J Am Coll Cardiol. 2015 May 26;65(20):2198-206. doi: 10.1016/j.jacc.2015.03.033. Epub 2015 Mar 15.
Abstract/Text BACKGROUND: In a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year.
OBJECTIVES: This study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis.
METHODS: We randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent (n = 300) or CABG (n = 300). The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) and compared on an intention-to-treat basis.
RESULTS: At 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative event rates of 17.5% and 14.3%, respectively; hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.84 to 1.90; p = 0.26). The 2 groups did not differ significantly in terms of death from any cause, myocardial infarction, or stroke as well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p = 0.66). Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively; HR: 2.11; 95% CI: 1.16 to 3.84; p = 0.012).
CONCLUSIONS: During 5 years of follow-up, our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG. However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT]; NCT00422968).

Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 25787197  J Am Coll Cardiol. 2015 May 26;65(20):2198-206. doi: 10・・・
著者: Edward L Hannan, Michael J Racz, Gary Walford, Robert H Jones, Thomas J Ryan, Edward Bennett, Alfred T Culliford, O Wayne Isom, Jeffrey P Gold, Eric A Rose
雑誌名: N Engl J Med. 2005 May 26;352(21):2174-83. doi: 10.1056/NEJMoa040316.
Abstract/Text BACKGROUND: Several studies have compared outcomes for coronary-artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), but most were done before the availability of stenting, which has revolutionized the latter approach.
METHODS: We used New York's cardiac registries to identify 37,212 patients with multivessel disease who underwent CABG and 22,102 patients with multivessel disease who underwent PCI from January 1, 1997, to December 31, 2000. We determined the rates of death and subsequent revascularization within three years after the procedure in various groups of patients according to the number of diseased vessels and the presence or absence of involvement of the left anterior descending coronary artery. The rates of adverse outcomes were adjusted by means of proportional-hazards methods to account for differences in patients' severity of illness before revascularization.
RESULTS: Risk-adjusted survival rates were significantly higher among patients who underwent CABG than among those who received a stent in all of the anatomical subgroups studied. For example, the adjusted hazard ratio for the long-term risk of death after CABG relative to stent implantation was 0.64 (95 percent confidence interval, 0.56 to 0.74) for patients with three-vessel disease with involvement of the proximal left anterior descending coronary artery and 0.76 (95 percent confidence interval, 0.60 to 0.96) for patients with two-vessel disease with involvement of the nonproximal left anterior descending coronary artery. Also, the three-year rates of revascularization were considerably higher in the stenting group than in the CABG group (7.8 percent vs. 0.3 percent for subsequent CABG and 27.3 percent vs. 4.6 percent for subsequent PCI).
CONCLUSIONS: For patients with two or more diseased coronary arteries, CABG is associated with higher adjusted rates of long-term survival than stenting.

Copyright 2005 Massachusetts Medical Society.
PMID 15917382  N Engl J Med. 2005 May 26;352(21):2174-83. doi: 10.1056・・・
著者: Paul Sorajja, Panithaya Chareonthaitawee, Navin Rajagopalan, Todd D Miller, Robert L Frye, David O Hodge, Raymond J Gibbons
雑誌名: Circulation. 2005 Aug 30;112(9 Suppl):I311-6. doi: 10.1161/CIRCULATIONAHA.104.525022.
Abstract/Text BACKGROUND: The Bypass Angioplasty Revascularization Investigation trial demonstrated that symptomatic diabetics with multivessel coronary artery disease had a survival advantage with initial coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI). No published study has examined different treatments and outcome in asymptomatic diabetics.
METHODS AND RESULTS: This study group consisted of 826 asymptomatic diabetics (age 62+/-12 years; 76% men) without known coronary artery disease who had abnormal myocardial perfusion during stress single photon emission computed tomography (SPECT). SPECT images were classified as low-, intermediate-, and high-risk. Early revascularization (CABG or PCI < or =4 months after SPECT) was performed in 76 patients. Survival (follow-up, 5.3+/-3.3 years) was compared in patients treated with CABG, PCI, or medical therapy. Revascularization (CABG or PCI) was performed in 54 of 261 patients with high-risk scans and was independently associated with improved survival (chi2=4.55; P=0.03 after multivariate adjustment). Subset analysis demonstrated that the survival advantage was confined to patients treated with CABG (n=39), with a 5-year survival CABG at 85%, PCI at 72%, and medical therapy at 67% (P=0.02 for 3 groups). Although CABG was associated with better survival, mortality remained high (3% per year). There was no survival advantage by treatment for patients with less-severe SPECT abnormalities.
CONCLUSIONS: These nonrandomized data suggest that CABG improves survival in asymptomatic diabetic patients with high-risk SPECT, although revascularization was performed infrequently in these patients. These results parallel those of the Bypass Angioplasty Revascularization Investigation trial in symptomatic diabetic patients.

PMID 16159837  Circulation. 2005 Aug 30;112(9 Suppl):I311-6. doi: 10.1・・・
著者:
雑誌名: Circulation. 1997 Sep 16;96(6):1761-9.
Abstract/Text BACKGROUND: Patients with diabetes mellitus have increased morbidity and mortality after coronary revascularization. The Bypass Angioplasty Revascularization Investigation (BARI), a trial of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG) in patients with multivessel disease, reported a 5-year survival advantage of CABG over PTCA in patients with treated diabetes mellitus (TDM). This report examines these findings in more detail.
METHODS AND RESULTS: Eighteen clinical centers randomly assigned 1829 patients with multivessel coronary disease to undergo initial CABG or PTCA. Patients were followed an average of 5.4 years. TDM was defined as a history of diabetes with use of oral hypoglycemic agents or insulin at study entry. Nineteen percent of the randomized population (353 patients) met these criteria. TDM patients had more unfavorable baseline characteristics than other patients, but among TDM patients, these characteristics were similar between the CABG and PTCA groups. Better average 5.4-year survival with CABG was due to reduced cardiac mortality (5.8% versus 20.6%, P=.0003), which was confined to those receiving at least one internal mammary artery graft.
CONCLUSIONS: Patients with TDM assigned to an initial strategy of CABG have a striking reduction in cardiac mortality compared with PTCA. Long-term internal mammary artery graft patency may contribute to this improved outcome by reducing the fatality of follow-up myocardial infarction.

PMID 9323059  Circulation. 1997 Sep 16;96(6):1761-9.
著者: Adrian P Banning, Stephen Westaby, Marie-Claude Morice, A Pieter Kappetein, Friedrich W Mohr, Sergio Berti, Mattia Glauber, Mirle A Kellett, Robert S Kramer, Katrin Leadley, Keith D Dawkins, Patrick W Serruys
雑誌名: J Am Coll Cardiol. 2010 Mar 16;55(11):1067-75. doi: 10.1016/j.jacc.2009.09.057. Epub 2010 Jan 14.
Abstract/Text OBJECTIVES: This study was designed to compare contemporary surgical revascularization (coronary artery bypass graft surgery [CABG]) versus TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stents (PES) in diabetic and nondiabetic patients with left main and/or 3-vessel disease.
BACKGROUND: Although the prevalence of diabetes mellitus is increasing, the optimal coronary revascularization strategy in diabetic patients with complex multivessel disease remains controversial.
METHODS: The SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) study randomly assigned 1,800 patients (452 with medically treated diabetes) to receive PES or CABG.
RESULTS: The overall 1-year major adverse cardiac and cerebrovascular event rate was higher among diabetic patients treated with PES compared with CABG, but the revascularization method did not impact the death/stroke/myocardial infarction rate for nondiabetic patients (6.8% CABG vs. 6.8% PES, p = 0.97) or for diabetic patients (10.3% CABG vs. 10.1% PES, p = 0.96). The presence of diabetes was associated with significantly increased mortality after either revascularization treatment. The incidence of stroke was higher among nondiabetic patients after CABG (2.2% vs. PES 0.5%, p = 0.006). Compared with CABG, mortality was higher after PES use for diabetic patients with highly complex lesions (4.1% vs. 13.5%, p = 0.04). Revascularization with PES resulted in higher repeat revascularization for nondiabetic patients (5.7% vs. 11.1%, p < 0.001) and diabetic patients (6.4% vs. 20.3%, p < 0.001).
CONCLUSIONS: Subgroup analyses suggest that the 1-year major adverse cardiac and cerebrovascular event rate is higher among diabetic patients with left main and/or 3-vessel disease treated with PES compared with CABG, driven by an increase in repeat revascularization. However, the composite safety end point (death/stroke/myocardial infarction) is comparable between the 2 treatment options for diabetic and nondiabetic patients. Although further study is needed, these exploratory results may extend the evidence for PES use in selected patients with less complex left main and/or 3-vessel lesions. (SYNergy Between PCI With TAXus and Cardiac Surgery [SYNTAX]; NCT00114972).

Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 20079596  J Am Coll Cardiol. 2010 Mar 16;55(11):1067-75. doi: 10.・・・
著者: Stuart N Hoffman, John A TenBrook, Michael P Wolf, Stephen G Pauker, Deeb N Salem, John B Wong
雑誌名: J Am Coll Cardiol. 2003 Apr 16;41(8):1293-304.
Abstract/Text OBJECTIVES: We performed a meta-analysis of randomized trials comparing coronary artery bypass graft surgery (CABG) with percutaneous transluminal coronary angioplasty (PTCA) for the treatment of coronary artery disease, incorporating new trials and examining long-term outcomes.
BACKGROUND: Previous meta-analyses of trials comparing CABG with PTCA have reported short- and intermediate-term outcomes, but since then longer term follow-up and newer trials have been published.
METHODS: We performed a meta-analysis of 13 randomized trials on 7,964 patients comparing PTCA with CABG.
RESULTS: We found a 1.9% absolute survival advantage favoring CABG over PTCA for all trials at five years (p < 0.02), but no significant advantage at one, three, or eight years. In subgroup analysis of multivessel disease, CABG provided significant survival advantage at both five and eight years. Patients randomized to PTCA had more repeat revascularizations at all time points (risk difference [RD] 24% to 38%, p < 0.001); with stents, this RD was reduced to 15% at one and three years. Stents also resulted in a significant decrease in nonfatal myocardial infarction at three years when compared with CABG. For diabetic patients, CABG provided a significant survival advantage over PTCA at 4 years but not at 6.5 years.
CONCLUSIONS: Our results suggest that, when compared with PTCA, CABG is associated with a lower five-year mortality, less angina, and fewer revascularization procedures. For patients with multivessel disease, CABG provided a survival advantage at five to eight years, and for diabetics, a survival advantage at four years. The addition of stents reduced the need for repeat revascularization by about half.

PMID 12706924  J Am Coll Cardiol. 2003 Apr 16;41(8):1293-304.
著者: Whady Hueb, Neuza Helena Lopes, Bernard J Gersh, Paulo Soares, Luiz A C Machado, Fabio B Jatene, Sergio A Oliveira, Jose A F Ramires
雑誌名: Circulation. 2007 Mar 6;115(9):1082-9. doi: 10.1161/CIRCULATIONAHA.106.625475.
Abstract/Text BACKGROUND: Despite routine use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), no conclusive evidence exists that either modality is superior to medical therapy (MT) alone for treating multivessel coronary artery disease with stable angina and preserved ventricular function.
METHODS AND RESULTS: The primary end points were total mortality, Q-wave myocardial infarction, or refractory angina requiring revascularization. The study comprised 611 patients randomly assigned to undergo CABG (n=203), PCI (n=205), or MT (n=203). At the 5-year follow-up, the primary end points occurred in 21.2% of patients who underwent CABG compared with 32.7% treated with PCI and 36% receiving MT alone (P=0.0026). No statistical differences were observed in overall mortality among the 3 groups. In addition, 9.4% of MT and 11.2% of PCI patients underwent repeat revascularization procedures compared with 3.9% of CABG patients (P=0.021). Moreover, 15.3%, 11.2%, and 8.3% of patients experienced nonfatal myocardial infarction in the MT, PCI, and CABG groups, respectively (P<0.001). The pairwise treatment comparisons of the primary end points showed no difference between PCI and MT (relative risk, 0.93; 95% confidence interval, 0.67 to 1.30) and a significant protective effect of CABG compared with MT (relative risk, 0.53; 95% confidence interval, 0.36 to 0.77).
CONCLUSIONS: All 3 treatment regimens yielded comparable, relatively low rates of death. MT was associated with an incidence of long-term events and rate of additional revascularization similar to those for PCI. CABG was superior to MT in terms of the primary end points, reaching a significant 44% reduction in primary end points at the 5-year follow-up of patients with stable multivessel coronary artery disease.

PMID 17339566  Circulation. 2007 Mar 6;115(9):1082-9. doi: 10.1161/CIR・・・
著者: David J Malenka, Bruce J Leavitt, Michael J Hearne, John F Robb, Yvon R Baribeau, Thomas J Ryan, Robert E Helm, Mirle A Kellett, Harold L Dauerman, Lawrence J Dacey, M Theodore Silver, Peter N VerLee, Paul W Weldner, Bruce D Hettleman, Elaine M Olmstead, Winthrop D Piper, Gerald T O'Connor, Northern New England Cardiovascular Disease Study Group
雑誌名: Circulation. 2005 Aug 30;112(9 Suppl):I371-6. doi: 10.1161/CIRCULATIONAHA.104.526392.
Abstract/Text BACKGROUND: Randomized trials comparing coronary artery bypass graft surgery (CABG) with percutaneous coronary interventions (PCIs) for patients with multivessel coronary disease (MVD) report similar long-term survival for CABG and PCI. These studies used a highly selected population of patients and providers, and their results may not be generalizable to actual care. Our goal in this study was to compare long-term survival of MVD patients treated with CABG vs PCI in contemporary practice.
METHODS AND RESULTS: From our northern New England registries of consecutive coronary revascularizations, we identified 10,198 CABG and 4,295 PCI patients with MVD who may have been eligible for either procedure between 1994 and 2001. Vital status was obtained by linkage to the National Death Index. Proportional-hazards regression was used to calculate hazard ratios (HRs) for survival in CABG vs PCI patients after adjustment for comorbidities and disease characteristics. CABG patients were older; had more comorbidities, more 3-vessel disease, and lower ejection fractions; and were more completely revascularized. Adjusted long-term survival for patients with 3-vessel disease was better after CABG than PCI (HR, 0.60; P<0.01) but not for patients with 2-vessel disease (HR, 0.98; P=0.77). The survival advantage of CABG for 3-vessel disease patients was present in all patient populations, including women, diabetics, and the elderly and in the era of high stent utilization.
CONCLUSIONS: In contemporary practice, survival for patients with 3-vessel coronary disease is better after CABG than PCI, an observation that patients and physicians should carefully consider when deciding on a revascularization strategy.

PMID 16159849  Circulation. 2005 Aug 30;112(9 Suppl):I371-6. doi: 10.1・・・
著者: N W Niles, P D McGrath, D Malenka, H Quinton, D Wennberg, S J Shubrooks, J F Tryzelaar, R Clough, M J Hearne, F Hernandez, M W Watkins, G T O'Connor, Northern New England Cardiovascular Disease Study Group
雑誌名: J Am Coll Cardiol. 2001 Mar 15;37(4):1008-15.
Abstract/Text OBJECTIVES: We sought to assess survival among patients with diabetes and multivessel coronary artery disease (MVD) after percutaneous coronary intervention (PCI) and after coronary artery bypass grafting surgery (CABG).
BACKGROUND: The Bypass Angioplasty Revascularization Investigation (BARI) demonstrated that diabetics with MVD survive longer after initial CABG than after initial PCI. Other randomized trials or observational databases have not conclusively reproduced this result.
METHODS: A large, regional database was linked to the National Death Index to assess five-year mortality. Of 7,159 consecutive patients with diabetes who underwent coronary revascularization in northern New England during 1992 to 1996, 2,766 (38.6%) were similar to those randomized in the BARI trial. Percutaneous coronary intervention was the initial revascularization strategy in 736 patients and CABG in 2,030. Cox proportional hazards regression was used to calculate risk-adjusted hazard ratios (HR) and 95% confidence intervals (CI 95%).
RESULTS: Patients who underwent PCI were younger, had higher ejection fractions and less extensive coronary disease. After adjusting for differences in baseline clinical characteristics, patients with diabetes treated with PCI had significantly greater mortality relative to those undergoing CABG (HR = 1.49; CI 95%: 1.02 to 2.17; p = 0.037). Mortality risk tended to increase more among 1,251 patients with 3VD (HR = 2.02; CI 95%: 1.04 to 3.91; p = 0.038) than among 1,515 patients with 2VD (HR = 1.33; CI 95%: 0.84 to 2.1; p = 0.21).
CONCLUSIONS: In this analysis of a large regional contemporary database of patients with diabetes selected to be similar to those enrolled in the BARI trial, five-year mortality was significantly increased after initial PCI. This supports the BARI conclusion on initial revascularization of patients with diabetes and MVD.

PMID 11263600  J Am Coll Cardiol. 2001 Mar 15;37(4):1008-15.
著者: W S Weintraub, B Stein, A Kosinski, J S Douglas, Z M Ghazzal, E L Jones, D C Morris, R A Guyton, J M Craver, S B King
雑誌名: J Am Coll Cardiol. 1998 Jan;31(1):10-9.
Abstract/Text OBJECTIVES: This study sought to compare the outcome of percutaneous transluminal coronary angioplasty (PTCA) (n = 834) and coronary artery bypass graft surgery (CABG) (n = 1805) in diabetic patients with multivessel coronary disease from an observational database.
BACKGROUND: There is concern about selection of revascularization in diabetic patients with multivessel coronary artery disease.
METHODS: Data were collected prospectively and entered into a computerized database. Follow-up was by letter or telephone or additional events resulting in readmission.
RESULTS: After CABG there were more in-hospital deaths (0.36% vs. 4.99%, p < 0.0001) and a trend toward more Q wave myocardial infarctions than after PTCA. Five- and 10-year survival rates were 78% and 45% after PTCA and 76% and 48% after CABG, respectively (p = 0.47). At 5 and 10 years, insulin-requiring patients had lower survival rates of 72% and 31% after PTCA and 70% and 48% after CABG, respectively (p = 0.54). Multivariate correlates of long-term mortality were older age, low left ventricular ejection fraction, heart failure and hypertension. In the total group, insulin requirement was a correlate of long-term mortality. For the total group, choice of therapy had a multivariate hazard ratio close to 1. In the insulin-requiring subgroup, the multivariate hazard ratio was 1.35 (95% confidence interval 1.01 to 1.79) for PTCA versus CABG. Corrected for baseline differences, 5- and 10-year survival rates were 68% and 36% after PTCA and 75% and 47% after CABG, respectively, in the insulin-requiring subgroup. Nonfatal events were more common after PTCA, especially additional revascularization.
CONCLUSIONS: This study reveals a high incidence of events in diabetic patients and raises further questions about angioplasty in insulin-requiring diabetic patients with multivessel disease.

PMID 9426011  J Am Coll Cardiol. 1998 Jan;31(1):10-9.
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: 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: 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: 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: Fikret Er, Amir M Nia, Henning Dopp, Martin Hellmich, Kristina M Dahlem, Evren Caglayan, Torsten Kubacki, Thomas Benzing, Erland Erdmann, Volker Burst, Natig Gassanov
雑誌名: Circulation. 2012 Jul 17;126(3):296-303. doi: 10.1161/CIRCULATIONAHA.112.096370. Epub 2012 Jun 26.
Abstract/Text BACKGROUND: Contrast medium-induced acute kidney injury is associated with substantial morbidity and mortality. The underlying mechanism has been attributed in part to ischemic kidney injury. The aim of this randomized, double-blind, sham-controlled trial was to assess the impact of remote ischemic preconditioning on contrast medium-induced acute kidney injury.
METHODS AND RESULTS: Patients with impaired renal function (serum creatinine >1.4 mg/dL or estimated glomerular filtration rate <60 mL · min(-1) · 1.73 m(-2)) undergoing elective coronary angiography were randomized in a 1:1 ratio to standard care with (n=50) or without ischemic preconditioning (n=50; intermittent arm ischemia through 4 cycles of 5-minute inflation and 5-minute deflation of a blood pressure cuff). Overall, both study groups were at high risk of developing contrast medium-induced acute kidney injury according to the Mehran risk score. The primary end point was the incidence of contrast medium-induced kidney injury, defined as an increase in serum creatinine ≥25% or ≥0.5 mg/dL above baseline at 48 hours after contrast medium exposure. Contrast medium-induced acute kidney injury occurred in 26 patients (26%), 20 (40%) in the control group and 6 (12%) in the remote ischemic preconditioning group (odds ratio, 0.21; 95% confidence interval, 0.07-0.57; P=0.002). No major adverse events were related to remote ischemic preconditioning.
CONCLUSIONS: Remote ischemic preconditioning before contrast medium use prevents contrast medium-induced acute kidney injury in high-risk patients. Our findings merit a larger trial to establish the effect of remote ischemic preconditioning on clinical outcomes.
CLINICAL TRIAL REGISTRATION: URL: http://www.germanctr.de. Unique identifier: U1111-1118-8098.

PMID 22735306  Circulation. 2012 Jul 17;126(3):296-303. doi: 10.1161/C・・・
著者: Toshiaki Yamanaka, Yusuke Kawai, Toru Miyoshi, Tsutomu Mima, Kenji Takagaki, Saori Tsukuda, Yukio Kazatani, Kazufumi Nakamura, Hiroshi Ito
雑誌名: Int J Cardiol. 2015 Jan 15;178:136-41. doi: 10.1016/j.ijcard.2014.10.135. Epub 2014 Oct 23.
Abstract/Text BACKGROUND: Contrast medium-induced acute kidney injury (CI-AKI) is a cardiovascular complication after myocardial infarction treated with emergency percutaneous coronary intervention. The aim of this randomized, sham-controlled trial was to evaluate the impact of remote ischemic preconditioning (RIPC) on CI-AKI in patients with ST-elevation myocardial infarction who received emergency primary percutaneous coronary intervention.
METHODS AND RESULTS: Patients with a suspected ST-elevation myocardial infarction were randomly assigned at a 1:1 ratio to receive percutaneous coronary intervention either with (n=63) or without (n=62) RIPC (intermittent arm ischemia through three cycles of 5min of inflation and 5min of deflation of a blood pressure cuff). A total of 47 RIPC patients and 47 control patients met all study criteria. The primary endpoint was the incidence of CI-AKI, which was defined as an increase in serum creatinine >0.5mg/dL or >25% over the baseline value 48-72h after administration of contrast medium. The incidence of CI-AKI was 10% (n=5) in the RIPC group and 36% (n=17) in the control group (p=0.003). The odds ratio of CI-AKI in patients who received RIPC was 0.18 (95% confidence interval: 0.05-0.64; p=0.008).
CONCLUSIONS: In patients with ST-elevation myocardial infarction, RIPC before percutaneous coronary intervention reduced the incidence of CI-AKI.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
PMID 25464237  Int J Cardiol. 2015 Jan 15;178:136-41. doi: 10.1016/j.i・・・
著者: Hanjun Pei, Yongjian Wu, Yingjie Wei, Yuejin Yang, Siyong Teng, Haitao Zhang
雑誌名: PLoS One. 2014;9(12):e115500. doi: 10.1371/journal.pone.0115500. Epub 2014 Dec 31.
Abstract/Text BACKGROUND: Results from randomized controlled trials (RCT) concerning cardiac and renal effect of remote ischemic preconditioning(RIPC) in patients with stable coronary artery disease(CAD) are inconsistent. The aim of this study was to explore whether RIPC reduce cardiac and renal events after elective percutaneous coronary intervention (PCI).
METHODS AND RESULTS: RCTs with data on cardiac or renal effect of RIPC in PCI were searched from Pubmed, EMBase, and Cochrane library (up to July 2014). Meta-regression and subgroup analysis were performed to identify the potential sources of significant heterogeneity(I(2) ≥ 40%). Eleven RCTs enrolling a total of 1713 study subjects with stable CAD were selected. Compared with controls, RIPC significantly reduced perioperative incidence of myocardial infarction (MI) [odds ratio(OR) = 0.68; 95% CI, 0.51 to 0.91; P = 0.01; I(2) = 41.0%] and contrast-induced acute kidney injury(AKI) (OR = 0.61; 95% CI, 0.38 to 0.98; P = 0.04; I(2) = 39.0%). Meta-regression and subgroup analyses confirmed that the major source of heterogeneity for the incidence of MI was male proportion (coefficient  = -0.049; P = 0.047; adjusted R(2) = 0.988; P = 0.02 for subgroup difference).
CONCLUSIONS: The present meta-analysis of RCTs suggests that RIPC may offer cardiorenal protection by reducing the incidence of MI and AKI in patients undergoing elective PCI. Moreover, this effect on MI is more pronounced in male subjects. Future high-quality, large-scale clinical trials should focus on the long-term clinical effect of RIPC.

PMID 25551671  PLoS One. 2014;9(12):e115500. doi: 10.1371/journal.pone・・・
著者: Yi Yang, Xia-Bing Lang, Ping Zhang, Rong Lv, Yong-Fei Wang, Jiang-Hua Chen
雑誌名: Am J Kidney Dis. 2014 Oct;64(4):574-83. doi: 10.1053/j.ajkd.2014.04.029. Epub 2014 Jun 20.
Abstract/Text BACKGROUND: Remote ischemic preconditioning (RIPC) to prevent acute kidney injury (AKI) following cardiac and vascular interventions is a controversial practice.
STUDY DESIGN: We conducted a systematic review and meta-analysis using the MEDLINE database (1966 through November 2013), EMBASE (1988 through November 2013), and Cochrane Library database.
SETTING & POPULATION: Patients undergoing cardiac and vascular interventions.
SELECTION CRITERIA FOR STUDIES: Randomized controlled trials comparing patient outcome with or without RIPC for prevention of AKI following cardiac and vascular interventions.
INTERVENTION: RIPC using an inflatable tourniquet around the limb or cross-clamping the iliac arteries versus non-RIPC.
OUTCOMES: AKI, need for renal replacement therapy, postoperative kidney biomarkers, in-hospital mortality, and length of intensive care unit and hospital stay.
RESULTS: 13 trials (1,334 participants) were included. RIPC decreased the risk of AKI for patients undergoing cardiac and vascular interventions compared with the control group (11 trials; 1,216 participants; risk ratio [RR], 0.70; 95% CI, 0.48-1.02; P = 0.06; I(2) = 45%) with marginal statistical significance. There were no differences in levels of postoperative kidney biomarkers (serum creatinine and glomerular filtration rate), incidence of renal replacement therapy, in-hospital mortality, hospital stay, or intensive care unit stay between the 2 groups. Metaregression analysis indicated that contrast intervention was not a covariate contributing significantly to heterogeneity on the risk estimate for AKI incidence; also, there was no dose effect of RIPC using tourniquet cuff around the limb on AKI prevention based on different ischemia duration.
LIMITATIONS: Different AKI definitions adopted in the trials included.
CONCLUSIONS: RIPC might be beneficial for the prevention of AKI following cardiac and vascular interventions, but the current evidence is not robust enough to make a recommendation. Adequately powered trials are needed to provide more evidence in the future.

Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
PMID 24954246  Am J Kidney Dis. 2014 Oct;64(4):574-83. doi: 10.1053/j.・・・
著者: Alexander Zarbock, Christoph Schmidt, Hugo Van Aken, Carola Wempe, Sven Martens, Peter K Zahn, Britta Wolf, Ulrich Goebel, Christian I Schwer, Peter Rosenberger, Helene Haeberle, Dennis Görlich, John A Kellum, Melanie Meersch, RenalRIPC Investigators
雑誌名: JAMA. 2015 Jun 2;313(21):2133-41. doi: 10.1001/jama.2015.4189.
Abstract/Text IMPORTANCE: No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery.
OBJECTIVE: To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery.
DESIGN, SETTING, AND PARTICIPANTS: In this multicenter trial, we enrolled 240 patients at high risk for acute kidney injury, as identified by a Cleveland Clinic Foundation score of 6 or higher, between August 2013 and June 2014 at 4 hospitals in Germany. We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning (control). All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle.
INTERVENTIONS: Patients received either remote ischemic preconditioning (3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia) or sham remote ischemic preconditioning (control), both via blood pressure cuff inflation.
MAIN OUTCOMES AND MEASURES: The primary end point was the rate of acute kidney injury defined by Kidney Disease: Improving Global Outcomes criteria within the first 72 hours after cardiac surgery. Secondary end points included use of renal replacement therapy, duration of intensive care unit stay, occurrence of myocardial infarction and stroke, in-hospital and 30-day mortality, and change in acute kidney injury biomarkers.
RESULTS: Acute kidney injury was significantly reduced with remote ischemic preconditioning (45 of 120 patients [37.5%]) compared with control (63 of 120 patients [52.5%]; absolute risk reduction, 15%; 95% CI, 2.56%-27.44%; P = .02). Fewer patients receiving remote ischemic preconditioning received renal replacement therapy (7 [5.8%] vs 19 [15.8%]; absolute risk reduction, 10%; 95% CI, 2.25%-17.75%; P = .01), and remote ischemic preconditioning reduced intensive care unit stay (3 days [interquartile range, 2-5]) vs 4 days (interquartile range, 2-7) (P = .04). There was no significant effect of remote ischemic preconditioning on myocardial infarction, stroke, or mortality. Remote ischemic preconditioning significantly attenuated the release of urinary insulinlike growth factor-binding protein 7 and tissue inhibitor of metalloproteinases 2 after surgery (remote ischemic preconditioning, 0.36 vs control, 0.97 ng/mL2/1000; difference, 0.61; 95% CI, 0.27-0.86; P < .001). No adverse events were reported with remote ischemic preconditioning.
CONCLUSIONS AND RELEVANCE: Among high-risk patients undergoing cardiac surgery, remote ischemic preconditioning compared with no ischemic preconditioning significantly reduced the rate of acute kidney injury and use of renal replacement therapy. The observed reduction in the rate of acute kidney injury and the need for renal replacement warrants further investigation.
TRIAL REGISTRATION: German Clinical Trials Register Identifier: DRKS00005333.

PMID 26024502  JAMA. 2015 Jun 2;313(21):2133-41. doi: 10.1001/jama.201・・・
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: Glenn N Levine, Eric R Bates, John A Bittl, Ralph G Brindis, Stephan D Fihn, Lee A Fleisher, Christopher B Granger, Richard A Lange, Michael J Mack, Laura Mauri, Roxana Mehran, Debabrata Mukherjee, L Kristin Newby, Patrick T O'Gara, Marc S Sabatine, Peter K Smith, Sidney C Smith, Jonathan L Halperin, Glenn N Levine, Sana M Al-Khatib, Kim K Birtcher, Biykem Bozkurt, Ralph G Brindis, Joaquin E Cigarroa, Lesley H Curtis, Lee A Fleisher, Federico Gentile, Samuel Gidding, Mark A Hlatky, John S Ikonomidis, José A Joglar, Susan J Pressler, Duminda N Wijeysundera
雑誌名: J Thorac Cardiovasc Surg. 2016 Nov;152(5):1243-1275. doi: 10.1016/j.jtcvs.2016.07.044.
Abstract/Text
PMID 27751237  J Thorac Cardiovasc Surg. 2016 Nov;152(5):1243-1275. do・・・
著者: John A Bittl, Usman Baber, Steven M Bradley, Duminda N Wijeysundera
雑誌名: J Am Coll Cardiol. 2016 Sep 6;68(10):1116-39. doi: 10.1016/j.jacc.2016.03.512. Epub 2016 Mar 29.
Abstract/Text BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after implantation of newer-generation drug-eluting stents (DES) remains uncertain. Similarly, questions remain about the role of DAPT in long-term therapy of stable post-myocardial infarction (MI) patients.
AIM: Our objective was to compare the incidence of death, major hemorrhage, MI, stent thrombosis, and major adverse cardiac events in patients randomized to prolonged or short-course DAPT after implantation of newer-generation DES and in secondary prevention after MI.
METHODS: We used traditional frequentist statistical and Bayesian approaches to address the following questions: Q1) What is the minimum duration of DAPT required after DES implantation? Q2) What is the clinical benefit of prolonging DAPT up to 18 to 48 months? Q3) What is the clinical effect of DAPT in stable patients who are >1 year past an MI?
RESULTS: We reviewed evidence from 11 randomized controlled trials (RCTs) that enrolled 33 051 patients who received predominantly newer-generation DES to answer: A1) Use of DAPT for 12 months, as compared with use for 3 to 6 months, resulted in no significant differences in incidence of death (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 0.85 to 1.63), major hemorrhage (OR: 1.65; 95% CI: 0.97 to 2.82), MI (OR: 0.87; 95% CI: 0.65 to 1.18), or stent thrombosis (OR: 0.87; 95% CI: 0.49 to 1.55). Bayesian models confirmed the primary analysis. A2) Use of DAPT for 18 to 48 months, compared with use for 6 to 12 months, was associated with no difference in incidence of all-cause death (OR: 1.14; 95% CI: 0.92 to 1.42) but was associated with increased major hemorrhage (OR: 1.58; 95% CI: 1.20 to 2.09), decreased MI (OR: 0.67; 95% CI: 0.47 to 0.95), and decreased stent thrombosis (OR: 0.45; 95% CI: 0.24 to 0.74). A risk-benefit analysis found 3 fewer stent thromboses (95% CI: 2 to 5) and 6 fewer MIs (95% CI: 2 to 11) but 5 more major bleeds (95% CI: 3 to 9) per 1000 patients treated with prolonged DAPT per year. Post hoc analyses provided weak evidence of increased mortality with prolonged DAPT. We reviewed evidence from 1 RCT of 21 162 patients and a post hoc analysis of 1 RCT of 15 603 patients to answer: A3): Use of DAPT >1 year after MI reduced the composite risk of cardiovascular death, MI, or stroke (hazard ratio: 0.84; 95% CI: 0.74 to 0.95) but increased major bleeding (hazard ratio: 2.32; 95% CI: 1.68 to 3.21). A meta-analysis and a post hoc analysis of an RCT in patients with stable cardiovascular disease produced similar findings.
CONCLUSIONS: The primary analysis provides moderately strong evidence that prolonged DAPT after implantation of newer-generation DES entails a tradeoff between reductions in stent thrombosis and MI and increases in major hemorrhage. Secondary analyses provide weak evidence of increased mortality with prolonged DAPT after DES implantation. In patients whose coronary thrombotic risk was defined by a prior MI rather than by DES implantation, the primary analysis provides moderately strong evidence of reduced cardiovascular events at the expense of increased bleeding.

Copyright © 2016 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.
PMID 27036919  J Am Coll Cardiol. 2016 Sep 6;68(10):1116-39. doi: 10.1・・・
著者: Laura Mauri, Dean J Kereiakes, Robert W Yeh, Priscilla Driscoll-Shempp, Donald E Cutlip, P Gabriel Steg, Sharon-Lise T Normand, Eugene Braunwald, Stephen D Wiviott, David J Cohen, David R Holmes, Mitchell W Krucoff, James Hermiller, Harold L Dauerman, Daniel I Simon, David E Kandzari, Kirk N Garratt, David P Lee, Thomas K Pow, Peter Ver Lee, Michael J Rinaldi, Joseph M Massaro, DAPT Study Investigators
雑誌名: N Engl J Med. 2014 Dec 4;371(23):2155-66. doi: 10.1056/NEJMoa1409312. Epub 2014 Nov 16.
Abstract/Text BACKGROUND: Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.
METHODS: Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.
RESULTS: A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.
CONCLUSIONS: Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).

PMID 25399658  N Engl J Med. 2014 Dec 4;371(23):2155-66. doi: 10.1056/・・・
著者: Dean J Kereiakes, Robert W Yeh, Joseph M Massaro, Priscilla Driscoll-Shempp, Donald E Cutlip, P Gabriel Steg, Anthony H Gershlick, Harald Darius, Ian T Meredith, John Ormiston, Jean Francois Tanguay, Stephan Windecker, Kirk N Garratt, David E Kandzari, David P Lee, Daniel I Simon, Adrian Corneliu Iancu, Jaroslaw Trebacz, Laura Mauri, Dual Antiplatelet Therapy (DAPT) Study Investigators
雑誌名: JAMA. 2015 Mar 17;313(11):1113-21. doi: 10.1001/jama.2015.1671.
Abstract/Text IMPORTANCE: Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown.
OBJECTIVE: To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses.
DESIGN, SETTING, AND PARTICIPANTS: International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014.
INTERVENTIONS: Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11,648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES.
MAIN OUTCOMES AND MEASURES: Stent thrombosis, MACCE, and moderate or severe bleeding.
RESULTS: Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n = 4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P = .24), rates of MACCE were 4.04% vs 4.69% (n = 33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P = .72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n = 16 vs 7; P = .07), respectively. Among all 11,648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32% (n = 23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P < .001), rates of MACCE were 4.29% vs 5.74% (n = 244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P < .001), and rates of moderate/severe bleeding were 2.45% vs 1.47% (n = 135 vs 80; P < .001).
CONCLUSIONS AND RELEVANCE: Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00977938.

PMID 25781440  JAMA. 2015 Mar 17;313(11):1113-21. doi: 10.1001/jama.20・・・
著者: Marco Valgimigli, Héctor Bueno, Robert A Byrne, Jean-Philippe Collet, Francesco Costa, Anders Jeppsson, Peter Jüni, Adnan Kastrati, Philippe Kolh, Laura Mauri, Gilles Montalescot, Franz-Josef Neumann, Mate Petricevic, Marco Roffi, Philippe Gabriel Steg, Stephan Windecker, Jose Luis Zamorano, Glenn N Levine, ESC Scientific Document Group
雑誌名: Eur J Cardiothorac Surg. 2018 Jan 1;53(1):34-78. doi: 10.1093/ejcts/ezx334.
Abstract/Text
PMID 29045581  Eur J Cardiothorac Surg. 2018 Jan 1;53(1):34-78. doi: 1・・・
著者: Jessica de Vries, Robert D Foreman, Mike J L DeJongste
雑誌名: Cleve Clin J Med. 2007 Feb;74 Suppl 1:S42-7.
Abstract/Text
PMID 17455543  Cleve Clin J Med. 2007 Feb;74 Suppl 1:S42-7.
著者: Mingyuan Wu, Bengt Linderoth, Robert D Foreman
雑誌名: Auton Neurosci. 2008 Feb 29;138(1-2):9-23. doi: 10.1016/j.autneu.2007.11.001.
Abstract/Text Spinal cord stimulation (SCS) is a widely used clinical technique to treat ischemic pain in peripheral, cardiac and cerebral vascular diseases. The use of this treatment advanced rapidly during the late 80's and 90's, particularly in Europe. Although the clinical benefits of SCS are clear and the success rate remains high, the mechanisms are not yet completely understood. SCS at lumbar spinal segments (L2-L3) produces vasodilation in the lower limbs and feet which is mediated by antidromic activation of sensory fibers and decreased sympathetic outflow. SCS at thoracic spinal segments (T1-T2) induces several benefits including pain relief, reduction in both frequency and severity of angina attacks, and reduced short-acting nitrate intake. The benefits to the heart are not likely due to an increase, or redistribution of local blood flow, rather, they are associated with SCS-induced myocardial protection and normalization of the intrinsic cardiac nervous system. At somewhat lower cervical levels (C3-C6), SCS induces increased blood flow in the upper extremities. SCS at the upper cervical spinal segments (C1-C2) increased cerebral blood flow, which is associated with a decrease in sympathetic activity, an increase in vasomotor center activity and a release of neurohumoral factors. This review will summarize the basic science studies that have contributed to our understanding about mechanisms through which SCS produces beneficial effects when used in the treatment of vascular diseases. Furthermore, this review will particularly focus on the antidromic mechanisms of SCS-induced vasodilation in the lower limbs and feet.

PMID 18083639  Auton Neurosci. 2008 Feb 29;138(1-2):9-23. doi: 10.1016・・・

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