今日の臨床サポート

無症候性心筋虚血

著者: 西村重敬 埼玉医科大学 心臓内科

監修: 代田浩之 順天堂大学大学院医学研究科循環器内科学

著者校正/監修レビュー済:2019/10/26
参考ガイドライン:
  1. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria for Coronary Revascularization in Patients with Stable Ischemic Heart Disease. J Am Coll Cardiol. 2017 69:2212-224.[1]
  1. 2018 ESC/EACTS Guidelines on myocardial Revascularization European Heart Journal (2019) 40, 87–165.[2]
  1. 日本循環器学会:循環器病の診断と治療に関するガイドライン 安定冠動脈疾患の血行再建ガイドライン(2018年改訂版)JCS 2018 Guideline on Revascularization of Stable Coronary Artery Disease2019 年3 月29 日発行[3]
  1. 日本循環器学会:循環器病の診断と治療に関するガイドライン慢性冠動脈疾患診断ガイドライン(2018年改訂版)JCS 2018 Guideline on Diagnosis of Chronic Coronary Heart Diseases 2019 年3 月29 日発行[4]
患者向け説明資料

概要・推奨   

  1. 心筋虚血(機能的心筋虚血)は、非観血的検査法である心電図、画像診断あるいは心カテーテル検査時の冠予備能検査等により診断できる。検査法の種類も増えたのと同時に、安定労作性狭心症を含む慢性冠動脈心患の至適内科治療への効果も証明された。従来から、慢性虚血性心疾患対するPCI治療による予後改善(死亡率減少および心筋梗塞発症予防)効果は明確でない。無症候性心筋虚血の病型のうち、狭心症に併存する病型では、血行再建で狭心痛と無症候性心筋虚血の改善が得られ、QOLは改善する。一方で、無症候性心筋虚血のみの病型に対にしては、虚血解除を目的としたルーチンの血行再建治療による生命予後改善効果を証明した無作為試験はないのが現状である。したがって、至適内科治療を基本として、心筋虚血の範囲・程度と冠動脈病変の評価からリスク層別化を行い、血行再建で生命予後が改善するハイリスク群での血行再建の適応を判断する。
  1. 心筋虚血を診断するために、Holter心電図検査、運動負荷心電図検査、負荷心筋シンチグラフィ(SPECT、PET)検査、負荷心筋灌流MRI検査が用いられる。無症候でかつ心筋虚血が証明されれば、無症候性心筋虚血と診断できる。
  1. 臨床所見による検査前有病率が低率である無症候例に対する、スクリーニングとしての安静時および負荷心電図検査は有用でない(推奨度3)。
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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:
西村重敬 : 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. 検査の進歩に伴う心筋虚血の診断法について追記した。
  1. 負荷心電図、Holter心電図から負荷画像診断(心筋シンチグラフィー:SPECT、PET、心エコー、MRI)
  1. 観血的心臓カテーテル検査時の最大充血時の血流予備量比(FFR)、安静時の瞬時血流予備量比(iFR)
  1. 冠動脈CT検査から算出されるFFR-CT
  1. 日本受循環器学会の慢性冠動脈疾患診断ガイドライン(2018年改訂版)と安定冠動脈疾患の血行再建ガイドライン(2018年改訂版)、欧州心臓病学会の血行再建ガイドライン(2019)、米国心臓病学会等の血行再建適正基準(2017)に基づき、リスク評価、治療方針について改訂した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 無症候性心筋虚血とは、冠動脈病変の存在により心筋への灌流が障害され虚血を呈するにもかかわらず、胸痛などの自覚症状を伴わないものを指す。
  1. 高齢者、糖尿病患者では頻度が高い。
  1. 心筋虚血時に狭心痛を感じないメカニズムは、痛みの閾値上昇、末梢性および中枢性の痛みの伝達機構等の異常による。
  1. 無症候性心筋虚血は、1960年代に開発されたHolter心電図(日常連続心電図)を用い、日常生活時の記録から診断されるようになり、1980年代から1990年代伝半に心電図を用いた研究が数多く行われた。当時の研究から提唱された患者背景因子を加味した臨床分類であるCohn分類では、Ⅰ型:全く無症状例、Ⅱ型:心筋梗塞後にみられる例、Ⅲ型:有症状の狭心症に併存する例、に分類される[5]
  1. 心筋虚血は時間経過とその程度により連鎖事象を引き起こす。灌流異常、局所壁運動異常、心電図異常と続き、 最終的に狭心痛が自覚される。(図<図表>
  1. 労作性狭心症、冠攣縮性狭心症、急性冠症候群、陳旧性心筋梗塞などの虚血性心疾患のあらゆる病型でみられる。
問診・診察のポイント  
  1. 完全に無症候なのか、狭心痛と同等の症状(息切れ、労作時呼吸困難等)の有無を診断する(胸痛に関するスコアの利用)。

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文献 

著者: Franz-Josef Neumann, Miguel Sousa-Uva, Anders Ahlsson, Fernando Alfonso, Adrian P Banning, Umberto Benedetto, Robert A Byrne, Jean-Philippe Collet, Volkmar Falk, Stuart J Head, Peter Jüni, Adnan Kastrati, Akos Koller, Steen D Kristensen, Josef Niebauer, Dimitrios J Richter, Petar M Seferovic, Dirk Sibbing, Giulio G Stefanini, Stephan Windecker, Rashmi Yadav, Michael O Zembala, ESC Scientific Document Group
雑誌名: Eur Heart J. 2019 Jan 7;40(2):87-165. doi: 10.1093/eurheartj/ehy394.
Abstract/Text
PMID 30165437  Eur Heart J. 2019 Jan 7;40(2):87-165. doi: 10.1093/eurh・・・
著者: Peter F Cohn, Kim M Fox, Caroline Daly
雑誌名: Circulation. 2003 Sep 9;108(10):1263-77. doi: 10.1161/01.CIR.0000088001.59265.EE.
Abstract/Text
PMID 12963683  Circulation. 2003 Sep 9;108(10):1263-77. doi: 10.1161/0・・・
著者: Roger Chou, Bhaskar Arora, Tracy Dana, Rongwei Fu, Miranda Walker, Linda Humphrey
雑誌名: Ann Intern Med. 2011 Sep 20;155(6):375-85. doi: 10.1059/0003-4819-155-6-201109200-00006.
Abstract/Text BACKGROUND: Coronary heart disease is the leading cause of death in adults. Screening for abnormalities by using resting or exercise electrocardiography (ECG) might help identify persons who would benefit from interventions to reduce cardiovascular risk.
PURPOSE: To update the 2004 U.S. Preventive Services Task Force evidence review on screening for resting or exercise ECG abnormalities in asymptomatic adults.
DATA SOURCES: MEDLINE (2002 through January 2011), the Cochrane Library database (through the fourth quarter of 2010), and reference lists.
STUDY SELECTION: Randomized, controlled trials and prospective cohort studies.
DATA EXTRACTION: Investigators abstracted details about the study population, study design, data analysis, follow-up, and results and assessed quality by using predefined criteria.
DATA SYNTHESIS: No study evaluated clinical outcomes or use of risk-reducing therapies after screening versus no screening. No study estimated how accurately resting or exercise electrocardiography classified participants into high-, intermediate-, or low-risk groups, compared with traditional risk factor assessment alone. Sixty-three prospective cohort studies evaluated abnormalities on resting or exercise ECG as predictors of cardiovascular events after adjustment for traditional risk factors. Abnormalities on resting ECG (ST-segment or T-wave abnormalities, left ventricular hypertrophy, bundle branch block, or left-axis deviation) or exercise ECG (ST-segment depression with exercise, chronotropic incompetence, abnormal heart rate recovery, or decreased exercise capacity) were associated with increased risk (pooled hazard ratio estimates, 1.4 to 2.1). Evidence on harms was limited, but direct harms seemed minimal (for resting ECG) or small (for exercise ECG). No study estimated harms from subsequent testing or interventions, although rates of angiography after exercise ECG ranged from 0.6% to 2.9%.
LIMITATIONS: Only English-language studies were included. Statistical heterogeneity was present in several of the pooled analyses.
CONCLUSION: Abnormalities on resting or exercise ECG are associated with an increased risk for subsequent cardiovascular events after adjustment for traditional risk factors, but the clinical implications of these findings are unclear.

PMID 21930855  Ann Intern Med. 2011 Sep 20;155(6):375-85. doi: 10.1059・・・
著者: Mehmet K Aktas, Volkan Ozduran, Claire E Pothier, Richard Lang, Michael S Lauer
雑誌名: JAMA. 2004 Sep 22;292(12):1462-8. doi: 10.1001/jama.292.12.1462.
Abstract/Text CONTEXT: The usefulness of exercise stress test results and global cardiovascular risk systems for predicting all-cause mortality in asymptomatic individuals seen in clinical settings is unclear.
OBJECTIVES: To determine the validity for prediction of all-cause mortality of the Framingham Risk Score and of a recently described European global scoring system Systematic Coronary Risk Evaluation (SCORE) for cardiovascular mortality among asymptomatic individuals evaluated in a clinical setting and to determine the potential prognostic value of exercise stress testing once these baseline risks are known.
DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 3554 asymptomatic adults between the ages of 50 and 75 years who underwent exercise stress testing as part of an executive health program between October 1990 and December 2002; participants were followed up for a mean of 8 years.
MAIN OUTCOME MEASURES: Global risk based on the Framingham Risk Score and the European SCORE. Prospectively recorded exercise stress test result abnormalities included impaired physical fitness, abnormal heart rate recovery, ventricular ectopy, and ST-segment abnormalities. The primary end point was all-cause mortality.
RESULTS: There were 114 deaths. The c-index, which corresponds to receiver operating characteristic curve values, and the Akaike Information Criteria found that the European SCORE was superior to the Framingham Risk Score in estimating global mortality risk. In a multivariable model, independent predictors of death were a higher SCORE (for 1% predicted increase in absolute risk, relative risk [RR], 1.07; 95% confidence interval [CI], 1.04-1.09; P<.001), impaired functional capacity (RR, 2.95; 95% CI, 1.98-4.39; P<.001), and an abnormal heart rate recovery (RR, 1.59; 95%, 1.04-2.41; P =.03). ST-segment depression did not predict mortality. Among patients in the highest tertile from the SCORE, an abnormal exercise stress test result, defined as either impaired functional capacity or an abnormal heart rate recovery, identified a mortality risk of more than 1% per year.
CONCLUSION: Exercise stress testing when combined with the European global risk SCORE may be useful for stratifying risk in asymptomatic individuals in a comprehensive executive health screening program.

PMID 15383517  JAMA. 2004 Sep 22;292(12):1462-8. doi: 10.1001/jama.292・・・
著者: Philip Greenland, Joseph S Alpert, George A Beller, Emelia J Benjamin, Matthew J Budoff, Zahi A Fayad, Elyse Foster, Mark A Hlatky, John McB Hodgson, Frederick G Kushner, Michael S Lauer, Leslee J Shaw, Sidney C Smith, Allen J Taylor, William S Weintraub, Nanette K Wenger, Alice K Jacobs, American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
雑誌名: Circulation. 2010 Dec 21;122(25):e584-636. doi: 10.1161/CIR.0b013e3182051b4c. Epub 2010 Nov 15.
Abstract/Text
PMID 21098428  Circulation. 2010 Dec 21;122(25):e584-636. doi: 10.1161・・・
著者: C J Pepine, P F Cohn, P C Deedwania, R S Gibson, E Handberg, J A Hill, E Miller, R G Marks, U Thadani
雑誌名: Circulation. 1994 Aug;90(2):762-8.
Abstract/Text BACKGROUND: Detection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome, but treatment of patients with asymptomatic ischemia remains controversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia.
METHODS AND RESULTS: A multicenter, randomized, double-blind, placebo-controlled study of asymptomatic or minimally symptomatic outpatients with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event-free survival at 1 year by Kaplan-Meier analysis. Events were death, resuscitated ventricular tachycardia/fibrillation, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization. The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks. Three hundred six outpatients with mild or no angina (Canadian Cardiovascular Society class I or II), abnormal exercise tests, and ischemia on ambulatory monitoring were randomized to receive either atenolol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean +/- SD, 3.6 +/- 4.2 versus 1.7 +/- 4.6 episodes, P < .001) and average duration (30 +/- 3.3 versus 16.4 +/- 6.7 minutes, P < .001) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients (4.4 +/- 4.6 to 3.1 +/- 6.0 episodes and 36.6 +/- 4.1 to 30 +/- 5.5 minutes). Event-free survival improved in atenolol-treated patients (P < .0066), who had an increased time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95% confidence intervals, 0.26 to 0.75; P = .001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillation, nonfatal myocardial infarction, or hospitalization for unstable angina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33; P = .175). The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generally similar comparing atenolol- and placebo-treated patients, although bradycardia was more frequent with atenolol.
CONCLUSIONS: Atenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.

PMID 8044945  Circulation. 1994 Aug;90(2):762-8.
著者: T Von Arnim
雑誌名: J Am Coll Cardiol. 1996 Jul;28(1):20-4.
Abstract/Text OBJECTIVES: The Total Ischemic Burden Bisoprolol Study (TIBBS) follow-up examined cardiac event rates in relation to transient ischemia and its treatment.
BACKGROUND: It is unclear whether transient ischemia on the ambulatory electrocardiogram has prognostic implications in stable angina and whether medical treatment can improve the prognosis.
METHODS: The TIBBS trial was an 8-week, randomized, controlled comparison of the effects of bisoprolol and nifedipine on transient ischemic episodes in patients with stable angina pectoris. Of the 545 patients screened, 520 (95.4%) could be followed up. Rates of cardiac and noncardiac death, nonfatal acute myocardial infarction, hospital admission for unstable angina and need for coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty were recorded.
RESULTS: A total of 145 events occurred in 120 (23.1%) of 520 patients. Patients with more than six episodes had an event rate of 32.5% compared with 25.0% for patients with two to six episodes and 13.2% for patients with less than two episodes (p < 0.001). Hard events (death, acute myocardial infarction, hospital admission for unstable angina pectoris) were more frequent in patients with two or more ischemic episodes (12.2% vs. 4.7%, p = 0.0049). Patients with a 100% response rate of transient ischemic episodes during the TIBBS trial had a 17.5% event rate at 1 year compared with 32.3% for non-100% responders (p = 0.008). Patients receiving bisoprolol during the TIBBS tria had a lower event rate (22.1%) at 1 year than patients randomized to nifedipine (33.1%, p = 0.033).
CONCLUSIONS: In patients with stable angina pectoris, frequent episodes of transient ischemia are a marker for an increased event rate. A 100% response to medical treatment reduces the event rate. The greater reduction of ischemia with bisoprolol than nifedipine during the TIBBS trial translated into an improved outcome at 1 year.

PMID 8752790  J Am Coll Cardiol. 1996 Jul;28(1):20-4.
著者: H J Dargie, I Ford, K M Fox
雑誌名: Eur Heart J. 1996 Jan;17(1):104-12.
Abstract/Text OBJECTIVE: To study the relationship between presence or absence of ischaemic events on Holter monitoring and occurrence of a hard or hard+soft endpoint.
DESIGN: A randomized double-blind parallel group study of atenolol, nifedipine and their combination, with ambulatory monitoring off-treatment and after 6 weeks of randomized treatment and prospective follow-up of 2 years on average.
SETTING: Europe.
SUBJECTS: 682 men and women with a diagnosis of chronic stable angina and who were not being considered for surgery.
MAIN OUTCOME: Hard endpoints were cardiac death, nonfatal myocardial infarction and unstable angina; soft endpoints were coronary artery bypass surgery, coronary angioplasty and treatment failure.
RESULTS: The study showed no evidence of an association between the presence, frequency or total duration of ischaemic events on Holter monitoring, either on or off treatment, and the main outcome measures. There was a non-significant trend to a lower rate of hard endpoints in the group receiving combination therapy. Compliance, as measured by withdrawal from trial medication, was clearly poorest in the nifedipine group with similar withdrawal rates in the atenolol and combination therapy groups.
CONCLUSION: The recording of ischaemic events in 48 h Holter monitoring failed to predict hard or hard+soft endpoints in patients with chronic stable angina.

PMID 8682116  Eur Heart J. 1996 Jan;17(1):104-12.
著者: L Forslund, P Hjemdahl, C Held, S V Eriksson, I Björkander, N Rehnqvist
雑誌名: Am J Cardiol. 1999 Nov 15;84(10):1151-7.
Abstract/Text The prognostic significance of ambulatory ischemia, alone and in relation to ischemia during exercise was assessed in 686 patients (475 men) with chronic stable angina pectoris taking part in the Angina Prognosis Study In Stockholm (APSIS), who had 24-hour ambulatory electrocardiographic registrations and exercise tests at baseline (n = 678) and after 1 month (n = 607) of double-blind treatment with metoprolol or verapamil. Ambulatory electrocardiograms were analyzed for ventricular premature complexes and ST-segment depression. During a median follow-up of 40 months, 29 patients died of cardiovascular (CV) causes, 27 had a nonfatal myocardial infarction, and 89 underwent revascularization. Patients with CV death had more episodes (median 5 vs. 1; p<0.01) and longer median duration (24 vs. 3 minutes; p<0.01) of ST-segment depression than patients without events. For those who had undergone revascularization, the duration was also longer (12 vs. 3 minutes; p<0.05). In a multivariate Cox model including sex, history of previous myocardial infarction, hypertension, and diabetes, the duration of ST-segment depression independently predicted CV death. When exercise testing was included, ambulatory ischemia carried additional prognostic information only among patients with ST-segment depression > or =2 mm during exercise. When the treatment given and treatment effects on ambulatory ischemia were added to the Cox model, no significant impact on prognosis was found. Ventricular premature complexes carried no prognostic information. Thus, in patients with stable angina pectoris, ischemia during ambulatory monitoring showed independent prognostic importance regarding CV death. Ambulatory electrocardiographic monitoring and exercise testing provide complementary information, but only among patients with marked ischemia during exercise. Treatment reduced ambulatory ischemia, but the short-term treatment effects did not significantly influence prognosis.

PMID 10569322  Am J Cardiol. 1999 Nov 15;84(10):1151-7.
著者: W J Rogers, M G Bourassa, T C Andrews, B D Bertolet, R S Blumenthal, B R Chaitman, S A Forman, N L Geller, A D Goldberg, G B Habib
雑誌名: J Am Coll Cardiol. 1995 Sep;26(3):594-605.
Abstract/Text OBJECTIVES: This report discusses the outcome at 1 year in patients in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study.
BACKGROUND: Comparative efficacy of medical therapy versus revascularization in treatment of asymptomatic ischemia is unknown. The ACIP study assessed the ability of three treatment strategies to suppress ambulatory electrocardiographic (ECG) ischemia to determine whether a large-scale trial studying the impact of these strategies on clinical outcomes was feasible.
METHODS: Five hundred fifty-eight patients with coronary anatomy amenable to revascularization, at least one episode of asymptomatic ischemia on the 48-h ambulatory ECG and ischemia on treadmill exercise testing were randomized to one of three treatment strategies: 1) medication to suppress angina (angina-guided strategy, n = 183); 2) medication to suppress both angina and ambulatory ECG ischemia (ischemia-guided strategy, n = 183); or 3) revascularization strategy (angioplasty or bypass surgery, n = 192). Medication was titrated atenolol-nifedipine or diltiazem-isosorbide dinitrate.
RESULTS: The revascularization group received less medication and had less ischemia on serial ambulatory ECG recordings and exercise testing than those assigned to the medical strategies. The ischemia-guided group received more medication but had suppression of ischemia similar to the angina-guided group. At 1 year, the mortality rate was 4.4% in the angina-guided group (8 of 183), 1.6% in the ischemia-guided group (3 of 183) and 0% in the revascularization group (overall, p = 0.004; angina-guided vs. revascularization, p = 0.003; other pairwise comparisons, p = NS). Frequency of myocardial infarction, unstable angina, stroke and congestive heart failure was not significantly different among the three strategies. The revascularization group had significantly fewer hospital admissions and nonprotocol revascularizations at 1 year. The incidence of death, myocardial infarction, nonprotocol revascularization or hospital admissions at 1 year was 32% with the angina-guided medical strategy, 31% with the ischemia-guided medical strategy and 18% with the revascularization strategy (p = 0.003).
CONCLUSIONS: After 1 year, revascularization was superior to both angina-guided and ischemia-guided medical strategies in suppressing asymptomatic ischemia and was associated with better outcome. These findings require confirmation by a larger scale trial.

PMID 7642848  J Am Coll Cardiol. 1995 Sep;26(3):594-605.
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: 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: S E Epstein, A A Quyyumi, R O Bonow
雑誌名: N Engl J Med. 1988 Apr 21;318(16):1038-43. doi: 10.1056/NEJM198804213181606.
Abstract/Text
PMID 3281012  N Engl J Med. 1988 Apr 21;318(16):1038-43. doi: 10.1056・・・
著者: C Richard Conti, Anthony A Bavry, John W Petersen
雑誌名: J Am Coll Cardiol. 2012 Jan 31;59(5):435-41. doi: 10.1016/j.jacc.2011.07.050.
Abstract/Text Myocardial ischemia can occur without overt symptoms. In fact, asymptomatic (or silent) ST-segment depression during ambulatory electrocardiogram monitoring occurs more often than symptomatic ST-segment depression in patients with coronary artery disease. Initial studies documented that silent ischemia provided independent prediction of adverse outcomes in patients with known and unknown coronary artery disease. The ACIP (Asymptomatic Cardiac Ischemia Pilot Study) enrolled patients in the 1990s and found that revascularization was better than medical therapy in reducing silent ischemic episodes and possibly cardiovascular (CV) events. However, the more recent COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found similar CV event rates between patients treated with optimal medical therapy alone and those treated with optimal medical therapy plus percutaneous revascularization. Therefore, in the current era, medical therapy appears to be as effective as revascularization in suppressing symptomatic ischemia and preventing CV events. COURAGE was not designed to evaluate changes in the frequency of silent ischemia. Therefore, silent ischemia may persist despite current-era treatment and might still identify patients with increased risk of CV events. Also, silent ischemia is likely to occur frequently in heart transplant patients with denervated hearts and coronary allograft vasculopathy, and future study aimed at improving the management of silent ischemia in this population is warranted. Additionally, future research is warranted to study the effect of newer medical therapies such as ranolazine or selected use of revascularization (for example, guided by fractional flow reserve) in those patients with persistent silent ischemia despite optimal current-era medical therapy.

Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 22281245  J Am Coll Cardiol. 2012 Jan 31;59(5):435-41. doi: 10.10・・・
著者: Paul Erne, Andreas W Schoenenberger, Dieter Burckhardt, Michel Zuber, Wolfgang Kiowski, Peter T Buser, Paul Dubach, Therese J Resink, Matthias Pfisterer
雑誌名: JAMA. 2007 May 9;297(18):1985-91. doi: 10.1001/jama.297.18.1985.
Abstract/Text CONTEXT: The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known.
OBJECTIVE: To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006.
INTERVENTIONS: Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin.
MAIN OUTCOME MEASURES: Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up.
RESULTS: During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up).
CONCLUSION: Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00387231.

PMID 17488963  JAMA. 2007 May 9;297(18):1985-91. doi: 10.1001/jama.297・・・
著者: Lawrence H Young, Frans J Th Wackers, Deborah A Chyun, Janice A Davey, Eugene J Barrett, Raymond Taillefer, Gary V Heller, Ami E Iskandrian, Steven D Wittlin, Neil Filipchuk, Robert E Ratner, Silvio E Inzucchi, DIAD Investigators
雑誌名: JAMA. 2009 Apr 15;301(15):1547-55. doi: 10.1001/jama.2009.476.
Abstract/Text CONTEXT: Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial.
OBJECTIVE: To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes.
DESIGN, SETTING, AND PATIENTS: The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007.
MAIN OUTCOME MEASURE: Cardiac death or nonfatal myocardial infarction (MI).
RESULTS: The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups.
CONCLUSION: In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00769275.

PMID 19366774  JAMA. 2009 Apr 15;301(15):1547-55. doi: 10.1001/jama.20・・・
著者: Steven P Sedlis, Pamela M Hartigan, Koon K Teo, David J Maron, John A Spertus, G B John Mancini, William Kostuk, Bernard R Chaitman, Daniel Berman, Jeffrey D Lorin, Marcin Dada, William S Weintraub, William E Boden, COURAGE Trial Investigators
雑誌名: N Engl J Med. 2015 Nov 12;373(20):1937-46. doi: 10.1056/NEJMoa1505532.
Abstract/Text BACKGROUND: Percutaneous coronary intervention (PCI) relieves angina in patients with stable ischemic heart disease, but clinical trials have not shown that it improves survival. Between June 1999 and January 2004, we randomly assigned 2287 patients with stable ischemic heart disease to an initial management strategy of optimal medical therapy alone (medical-therapy group) or optimal medical therapy plus PCI (PCI group) and did not find a significant difference in the rate of survival during a median follow-up of 4.6 years. We now report the rate of survival among the patients who were followed for up to 15 years.
METHODS: We obtained permission from the patients at the Department of Veterans Affairs (VA) sites and some non-VA sites in the United States to use their Social Security numbers to track their survival after the original trial period ended. We searched the VA national Corporate Data Warehouse and the National Death Index for survival information and the dates of death from any cause. We calculated survival according to the Kaplan-Meier method and used a Cox proportional-hazards model to adjust for significant between-group differences in baseline characteristics.
RESULTS: Extended survival information was available for 1211 patients (53% of the original population). The median duration of follow-up for all patients was 6.2 years (range, 0 to 15); the median duration of follow-up for patients at the sites that permitted survival tracking was 11.9 years (range, 0 to 15). A total of 561 deaths (180 during the follow-up period in the original trial and 381 during the extended follow-up period) occurred: 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (adjusted hazard ratio, 1.03; 95% confidence interval, 0.83 to 1.21; P=0.76).
CONCLUSIONS: During an extended-follow-up of up to 15 years, we did not find a difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone in patients with stable ischemic heart disease. (Funded by the VA Cooperative Studies Program and others; COURAGE ClinicalTrials.gov number, NCT00007657.).

PMID 26559572  N Engl J Med. 2015 Nov 12;373(20):1937-46. doi: 10.1056・・・
著者: Gilbert Gosselin, Koon K Teo, Jean-Francois Tanguay, Rohit Gokhale, Pamela M Hartigan, David J Maron, Vipul Gupta, G B John Mancini, Eric R Bates, Bernard R Chaitman, John A Spertus, William J Kostuk, Marcin Dada, Steven P Sedlis, Daniel S Berman, Leslee J Shaw, Robert A O'Rourke, William S Weintraub, William E Boden, COURAGE Trial Investigators
雑誌名: Am J Cardiol. 2012 Apr 1;109(7):954-9. doi: 10.1016/j.amjcard.2011.11.023.
Abstract/Text Previous studies have suggested that percutaneous coronary intervention (PCI) decreases long-term mortality in patients with silent myocardial ischemia (SMI), but whether PCI specifically decreases mortality when added to intensive medical therapy is unknown. We performed a post hoc analysis of clinical outcomes in patients in the COURAGE trial based on the presence or absence of anginal symptoms at baseline. Asymptomatic patients were classified as having SMI by electrocardiographic ischemia at rest or reversible stress perfusion imaging (exercise-induced or pharmacologic). Study end points included the composite primary end point (death or myocardial infarction [MI]); individual end points of death, MI, and hospitalization for acute coronary syndrome; and need for revascularization. Of 2,280 patients 12% (n = 283) had SMI and 88% were symptomatic (n = 1,997). There were no between-group differences in age, gender, cardiac risk factors, previous MI or revascularization, extent of angiographic disease, or ischemia by electrocardiogram or imaging. Compared to symptomatic patients, those with SMI had fewer subsequent revascularizations (16% vs 27%, p <0.001) regardless of treatment assignment and fewer hospitalizations for acute coronary syndrome (7% vs 12%, p <0.04). No significant differences in outcomes were observed between the 2 treatment groups, although there was a trend toward fewer deaths in the PCI group (n = 7, 5%) compared to the optimal medical therapy (OMT) group (n = 16, 11%, p = 0.12). In conclusion, addition of PCI to OMT did not decrease nonfatal cardiac events in patients with SMI but showed a trend toward fewer deaths. Although underpowered, given similar outcomes in other small studies, these findings suggest the need for an adequately powered trial of revascularization versus OMT in SMI patients.

Published by Elsevier Inc.
PMID 22445578  Am J Cardiol. 2012 Apr 1;109(7):954-9. doi: 10.1016/j.a・・・
著者: Demosthenes G Katritsis, Daniel B Mark, Bernard J Gersh
雑誌名: Nat Rev Cardiol. 2018 Jul;15(7):408-419. doi: 10.1038/s41569-018-0006-z.
Abstract/Text Although revascularization has been one of the primary treatment options for obstructive coronary artery disease (CAD) for about 50 years, the evidence base for its use is most robust in the area of acute coronary disease. By contrast, evidence - particularly from clinical trials - supporting the use of revascularization to improve clinical outcomes in stable CAD is in some important respects outdated in that it reflects therapies that predate both contemporary standards for optimal medical therapy and current revascularization techniques and technologies. Despite such limitations, these clinical trials still provide the foundation for many of the current guideline-based indications for coronary revascularization in patients with stable CAD. In this Review, we discuss the major factors underlying the clinical decision to perform revascularization in patients with stable CAD and examine the use and limitations of existing evidence on the choice for, and preferred methods of, revascularization, namely, CABG surgery versus percutaneous coronary intervention.

PMID 29654257  Nat Rev Cardiol. 2018 Jul;15(7):408-419. doi: 10.1038/s・・・
著者: Rasha K Al-Lamee, Alexandra N Nowbar, Darrel P Francis
雑誌名: Heart. 2019 Jan;105(1):11-19. doi: 10.1136/heartjnl-2017-312755. Epub 2018 Sep 21.
Abstract/Text The adverse consequences of stable coronary artery disease (CAD) are death, myocardial infarction (MI) and angina. Trials in stable CAD show that percutaneous coronary intervention (PCI) does not reduce mortality. PCI does appear to reduce spontaneous MI rates but at the expense of causing some periprocedural MI. Therefore, the main purpose of PCI is to relieve angina. Indeed, patients and physicians often choose PCI rather than first attempting to control symptoms with anti-anginal medications as recommended by guidelines. Nevertheless, it is unclear how effective PCI is at relieving angina. This is because, whereas anti-anginal medications are universally required to be tested against placebo, there is no such requirement for procedural interventions such as PCI. The first placebo-controlled trial of PCI showed a surprisingly small effect size. This may be because it is overly simplistic to assume that the presence of a stenosis and inducible ischaemia in a patient means that the clinical chest pain they report is caused by ischaemia. In this article, we review the evidence base and argue that if we as a medical specialty wish to lead the science of procedures for symptom control, we should recognise the special merit of placebo-controlled experiments.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
PMID 30242142  Heart. 2019 Jan;105(1):11-19. doi: 10.1136/heartjnl-201・・・
著者: Kathleen Stergiopoulos, William E Boden, Pamela Hartigan, Sven Möbius-Winkler, Rainer Hambrecht, Whady Hueb, Regina M Hardison, J Dawn Abbott, David L Brown
雑誌名: JAMA Intern Med. 2014 Feb 1;174(2):232-40. doi: 10.1001/jamainternmed.2013.12855.
Abstract/Text IMPORTANCE: Myocardial ischemia in patients with stable coronary artery disease (CAD) has been repeatedly associated with impaired survival. However, it is unclear if revascularization with percutaneous coronary intervention (PCI) to relieve ischemia improves outcomes compared with medical therapy (MT).
OBJECTIVE: The objective of this study was to compare the effect of PCI and MT with MT alone exclusively in patients with stable CAD and objectively documented myocardial ischemia on clinical outcomes.
DATA SOURCES: MEDLINE, Cochrane, and PubMed databases from 1970 to November 2012. Unpublished data were obtained from investigators.
STUDY SELECTION: Randomized clinical trials of PCI and MT vs MT alone for stable coronary artery disease in which stents and statins were used in more than 50% of patients.
DATA EXTRACTION: For studies in which myocardial ischemia diagnosed by stress testing or fractional flow reserve was required for enrollment, descriptive and quantitative data were extracted from the published report. For studies in which myocardial ischemia was not a requirement for enrollment, authors provided data for only those patients with ischemia determined by stress testing prior to randomization. The outcomes analyzed included death from any cause, nonfatal myocardial infarction (MI), unplanned revascularization, and angina. Summary odds ratios (ORs) were obtained using a random-effects model. Heterogeneity was assessed using the Q statistic and I2.
RESULTS: In 5 trials enrolling 5286 patients, myocardial ischemia was diagnosed in 4064 patients by exercise stress testing, nuclear or echocardiographic stress imaging, or fractional flow reserve. Follow-up ranged from 231 days to 5 years (median, 5 years). The respective event rates for PCI with MT vs MT alone for death were 6.5% and 7.3% (OR, 0.90 [95% CI, 0.71-1.16); for nonfatal MI, 9.2% and 7.6% (OR, 1.24 [95% CI, 0.99-1.56]); for unplanned revascularization, 18.3% and 28.4% (OR, 0.64 [95% CI, 0.35-1.17); and for angina, 20.3% and 23.3% (OR, 0.91 [95% CI, 0.57-1.44]).
CONCLUSIONS AND RELEVANCE: In patients with stable CAD and objectively documented myocardial ischemia, PCI with MT was not associated with a reduction in death, nonfatal MI, unplanned revascularization, or angina compared with MT alone.

PMID 24296791  JAMA Intern Med. 2014 Feb 1;174(2):232-40. doi: 10.1001・・・
著者: Panagiotis Xaplanteris, Stephane Fournier, Nico H J Pijls, William F Fearon, Emanuele Barbato, Pim A L Tonino, Thomas Engstrøm, Stefan Kääb, Jan-Henk Dambrink, Gilles Rioufol, Gabor G Toth, Zsolt Piroth, Nils Witt, Ole Fröbert, Petr Kala, Axel Linke, Nicola Jagic, Martin Mates, Kreton Mavromatis, Habib Samady, Anand Irimpen, Keith Oldroyd, Gianluca Campo, Martina Rothenbühler, Peter Jüni, Bernard De Bruyne, FAME 2 Investigators
雑誌名: N Engl J Med. 2018 Jul 19;379(3):250-259. doi: 10.1056/NEJMoa1803538. Epub 2018 May 22.
Abstract/Text BACKGROUND: We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease.
METHODS: Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.
RESULTS: A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy.
CONCLUSIONS: In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

PMID 29785878  N Engl J Med. 2018 Jul 19;379(3):250-259. doi: 10.1056/・・・
著者: Rasha Al-Lamee, David Thompson, Hakim-Moulay Dehbi, Sayan Sen, Kare Tang, John Davies, Thomas Keeble, Michael Mielewczik, Raffi Kaprielian, Iqbal S Malik, Sukhjinder S Nijjer, Ricardo Petraco, Christopher Cook, Yousif Ahmad, James Howard, Christopher Baker, Andrew Sharp, Robert Gerber, Suneel Talwar, Ravi Assomull, Jamil Mayet, Roland Wensel, David Collier, Matthew Shun-Shin, Simon A Thom, Justin E Davies, Darrel P Francis, ORBITA investigators
雑誌名: Lancet. 2018 Jan 6;391(10115):31-40. doi: 10.1016/S0140-6736(17)32714-9. Epub 2017 Nov 2.
Abstract/Text BACKGROUND: Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy.
METHODS: ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593.
FINDINGS: ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group.
INTERPRETATION: In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.
FUNDING: NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre.

Copyright © 2018 Elsevier Ltd. All rights reserved.
PMID 29103656  Lancet. 2018 Jan 6;391(10115):31-40. doi: 10.1016/S0140・・・

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ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから