PCI (optimal catheter-based coronary revascularization) + intensive medical therapy is superior to intensive medical therapy alone using the combined endpoint of all-cause mortality or nonfatal MI.

Primary Hypothesis: The strategy of PCI plus intensive medical therapy will be superior to intensive medical therapy alone in reducing all cause mortality or nonfatal MI in patients with documented myocardial ischemia who meet an AHA task force Class I indication for PCI.

Secondary Hypotheses: Resource utilization and QOL comparisons and hospitalization for acute coronary syndromes will be superior in PCI plus medical therapy compared to medical therapy alone.

Primary Outcomes: All cause mortality, nonfatal MI.

Interventions: All patients will be treated with intensive medical therapy. In addition half of them will receive percutaneous coronary intervention (PCI).

Study Abstract: The COURAGE Trial is a large-scale, multicenter, randomized controlled trial comparing medical therapy and PCI plus medical therapy that is powered for "hard" clinical endpoints. Patients eligible for inclusion in COURAGE will comprise all but very high-risk subjects, and will include those with chronic angina pectoris (Canadian Cardiovascular Society [CCS] Class I-III), recent uncomplicated MI, and asymptomatic (or "silent") myocardial ischemia. Patients may have single- or multi-vessel coronary artery disease and may have had prior bypass graft surgery or PCI. We project cumulative 3-year event rates of 16.4% and 21%, respectively, which yields an absolute difference of 4.6% or relative difference of 22%. With a minimum duration of follow-up of 2 1/2 years, a maximum of 7 years, using a two-sided test of significance at the 0.05 level, and assuming a 3% crossover rate then 2% then 1% each for 2 years from meds to PCI, and annual loss to follow-up rate of 1% these event rates indicate that a sample size of 2,270 will be needed to test the hypothesis with 85% power. Fifteen VA, 19 U.S. non-VA, and 16 Canadian sites enrolled in the study. The planned study duration was 7 years, with 4 1/2 years of patient intake and 2 1/2 - 7 years of follow-up. Study operations began in January 1999 and enrollment began in June 1999. The Data and Safety Monitoring Board approved reducing the sample size to 2,270 subjects based on increasing the length of randomization and follow-up and updating the definition of MI to include biomarker positive (troponin) ACS. Enrollment is complete with 2,287 patients enrolled.

• Procedure: Intensive medical therapy
• Procedure: Percutaneous Coronary Intervention (PCI) plus intensive medical therapy

• Experimental: Percutaneous Coronary Intervention (PCI) plus intensive medical therapy
• Active Comparator: Intensive medical therapy

• Teo KK, Sedlis SP, Boden WE, O'Rourke RA, Maron DJ, Hartigan PM, Dada M, Gupta V, Spertus JA, Kostuk WJ, Berman DS, Shaw LJ, Chaitman BR, Mancini GB, Weintraub WS; COURAGE Trial Investigators. Optimal medical therapy with or without percutaneous coronary intervention in older patients with stable coronary disease: a pre-specified subset analysis of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial. J Am Coll Cardiol. 2009 Sep 29;54(14):1303-8.
• Weintraub WS, Spertus JA, Kolm P, Maron DJ, Zhang Z, Jurkovitz C, Zhang W, Hartigan PM, Lewis C, Veledar E, Bowen J, Dunbar SB, Deaton C, Kaufman S, O'Rourke RA, Goeree R, Barnett PG, Teo KK, Boden WE; COURAGE Trial Research Group; Mancini GB. Effect of PCI on quality of life in patients with stable coronary disease. N Engl J Med. 2008 Aug 14;359(7):677-87.
• Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, Hartigan PM, Weintraub WS, O'Rourke RA, Dada M, Spertus JA, Chaitman BR, Friedman J, Slomka P, Heller GV, Germano G, Gosselin G, Berger P, Kostuk WJ, Schwartz RG, Knudtson M, Veledar E, Bates ER, McCallister B, Teo KK, Boden WE; COURAGE Investigators. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation. 2008 Mar 11;117(10):1283-91. Epub 2008 Feb 11.
• Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007 Apr 12;356(15):1503-16. Epub 2007 Mar 26.

Inclusion Criteria:

• Patients eligible for inclusion in COURAGE will comprise all but very high-risk subjects, and will include those with chronic angina pectoris (Canadian Cardiovascular Society [CCS] Class I-III), uncomplicated MI, cooled down ACS, and asymptomatic (or "silent") myocardial ischemia.
• Patients may have single- or multi-vessel coronary artery disease and may have had prior bypass graft surgery or PCI.

It is important to emphasize that as many types of CAD patients as possible--reflecting the spectrum of patients encountered in contemporary clinical practice--will be enrolled in COURAGE.

Exclusion Criteria:

• Medical Research Council of Canada
• Merck
• Pfizer
• GE Healthcare
• Bristol-Myers Squibb
• Astellas Pharma Inc
• AstraZeneca
• Sanofi-Aventis
• Datascope Corp.
• First Horizon
• Kos
• Key Pharmaceuticals
• Integrated Therapeutics Group
• Hoest-Marion-Roussel