N Engl J Med 2007;356:1503-1516Background: By the turn of the 21st century more than 1 million coronary stent procedures were performed each year in the United States and approximately 85% were undertaken electively in patients with stable coronary artery disease. This pattern evolved without a single clinical trial demonstrating a concrete improvement in hard endpoints with percutaneous coronary intervention (PCI) compared to optimal medical therapy (OMT) alone. We have already reviewed several of these trials including ACME, RITA-2 and the Atorvastatin vs Angioplasty trial. Each trial was relatively small and none showed a significant benefit for revascularization compared to medical therapy on death or MI.Previous trials involving PCI compared to standard care or OMT included less than 3,000 patients altogether, did not broadly use intracoronary stents (instead using balloon angioplasty only) and they did not employ what would be considered a contemporary standard of medical management. Thus many questions involving the efficacy and safety of PCI versus OMT alone for managing stable CAD remained unanswered.The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial was designed to test the hypothesis that up front PCI plus OMT would significantly reduce the risk of death and nonfatal MI compared to OMT alone in patients with stable CAD.Cardiology Trial’s Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients: Eligible patients had stable CAD defined as either 1) a coronary stenosis of >/= 70% in one or more proximal epicardial coronary arteries and objective evidence of myocardial ischemia (based on the resting ECG or with exercise or pharmacologic vasodilator stress testing) or 2) a coronary stenosis of >/= 80% and classic angina without provocative testing. Patients were excluded if they had persistent Canadian Cardiovascular Society (CCS) class IV angina, a markedly positive stress test defined by substantial ST-segment depression or hypotensive response during stage 1 of the Bruce protocol), refractory heart failure or cardiogenic shock, an EF =30%, revascularization within 6 months, and coronary anatomy not suitable for PCI.Baseline characteristics: The average age of patients was 61 years of age, 85% were men and 85% were white. The average EF was 61%. The median time from the first episode of angina before randomization was 5 months (median, 3 episodes per week, with exertion or at rest). Fifty eight percent of patients had CCS class II or III angina. Eighty five percent of patients underwent stress testing at baseline. Of these, 70% underwent nuclear imaging. In patients who underwent nuclear imaging, 66% had multiple reversible defects and 23% had a single reversible defect. Angiographic data is as follows, approximately 30% of patients had single vessel disease, 40% had 2 vessel disease, and 30% had 3 vessel disease. The proportion of patients with proximal LAD disease was unbalanced between groups with the medical therapy group having a significantly higher percentage (37% vs 31%; p=0.01). Eleven percent of all patients had a previous CABG and among these participants 65% had disease in a graft. Procedures: Patients were randomly assigned to undergo PCI and OMT (PCI group) or OMT alone (OMT group). Patients were stratified by study site and whether they had a previous CABG. All patients received antiplatelet therapy with aspirin (81 to 325 mg per day) or clopidogrel (75 mg per day), if aspirin intolerant. Patients undergoing PCI received aspirin and clopidogrel in accordance with accepted standards. Medical anti-ischemic therapy in both groups included long-acting metoprolol, amlodipine, and isosorbide mononitrate alone or in combination, along with either lisinopril or losartan as standard secondary prevention. All patients received therapy to lower LDL with simvastatin alone or in combinatio