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Background: Extent and severity of myocardial ischemia are determinants of risk for patients with coronary artery disease, and ischemia reduction is an important therapeutic goal. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) nuclear substudy compared the effectiveness of percutaneous coronary intervention (PCI) for ischemia reduction added to optimal medical therapy (OMT) with the use of myocardial perfusion single photon emission computed tomography (MPS)., Methods and Results: Of the 2287 COURAGE patients, 314 were enrolled in this substudy of serial rest/stress MPS performed before treatment and 6 to 18 months (mean=374+/-50 days) after randomization using paired exercise (n=84) or vasodilator stress (n=230). A blinded core laboratory analyzed quantitative MPS measures of percent ischemic myocardium. Moderate to severe ischemia encumbered > or = 10% myocardium. The primary end point was > or = 5% reduction in ischemic myocardium at follow-up. Treatment groups had similar baseline characteristics. At follow-up, the reduction in ischemic myocardium was greater with PCI+OMT (-2.7%; 95% confidence interval, -1.7%, -3.8%) than with OMT (-0.5%; 95% confidence interval, -1.6%, 0.6%; P<0.0001). More PCI+OMT patients exhibited significant ischemia reduction (33% versus 19%; P=0.0004), especially patients with moderate to severe pretreatment ischemia (78% versus 52%; P=0.007). Patients with ischemia reduction had lower unadjusted risk for death or myocardial infarction (P=0.037 [risk-adjusted P=0.26]), particularly if baseline ischemia was moderate to severe (P=0.001 [risk-adjusted P=0.08]). Death or myocardial infarction rates ranged from 0% to 39% for patients with no residual ischemia to > or = 10% residual ischemia on follow-up MPS (P=0.002 [risk-adjusted P=0.09])., Conclusions: In COURAGE patients who underwent serial MPS, adding PCI to OMT resulted in greater reduction in ischemia compared with OMT alone. Our findings suggest a treatment target of > or = 5% ischemia reduction with OMT with or without coronary revascularization.

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.)

Major improvements in medical therapy and percutaneous coronary intervention for coronary artery disease (CAD) have emerged during the previous 2 decades, but no randomized trial in patients with stable CAD has been powered to compare these 2 strategies for the hard clinical end points of death or myocardial infarction (MI), and previous studies have not evaluated the effect of coronary stents and intensive medical therapy on cardiac events during long-term follow-up. Between 1999 and 2004, 2,287 patients with documented myocardial ischemia and angiographically confirmed CAD were randomized to the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial, with a principal hypothesis that a strategy of percutaneous coronary intervention plus intensive, guideline-driven medical therapy would be superior to a strategy of intensive medical therapy alone. The primary end point was a composite of all-cause mortality or acute MI (time to first event) during a 2.5- to 7-year (median 5) follow-up. Baseline characteristics were a mean age of 62 +/- 5 years, 85% men, and 86% Caucasian. Mean duration of angina before randomization was 26 months (average 10 episodes/week), and 29% of patients were smokers, 67% had hypertension, 38% had previous MI, 71% had dyslipidemia, 34% had diabetes, 27% had previous revascularization, and 69% had multivessel CAD. Approximately 55% of patients met established criteria for the metabolic syndrome. In conclusion, baseline characteristics of the COURAGE trial study population indicate a highly symptomatic group of patients with CAD who have a significant duration and frequency of antecedent angina pectoris and a high prevalence of cardiac risk factors.

Background: Coronary heart disease (CHD) and diabetes may have synergistic effects on symptoms, self-management, and general and cardiac-specific health status., Purpose: We compared symptom distress, self-management difficulties, and general and cardiac-specific health status in patients with CHD by the presence and severity of diabetes., Methods: We performed a cross-sectional study of 1013 patients enrolled in the COURAGE trial, with the use of clinical data, the Symptom Distress Scale, the Self-Management Difficulties Scale, the Short-Form 36, and the Seattle Angina Questionnaire., Results: Patients with diabetes and greater severity of diabetes had worse findings in symptom distress, self-management difficulties, and general and cardiac-specific health status than patients without diabetes., Conclusions: A robust effect of diabetes on symptom distress and self-management difficulties was found in patients with CHD. The results from the Seattle Angina Questionnaire illustrate difficulty in attributing physical limitations to specific symptoms or conditions, and show the experience of comorbid conditions to be synergistic. Clinicians' understanding of this synergy and integration of condition-specific care with general treatment and self-management practices are needed.

Background: Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial., Methods and Results: The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n = 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients' ischemic burdens., Conclusions: The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease.

Background: Major improvements in medical therapy and percutaneous coronary intervention (PCI) for coronary heart disease have occurred during the past decade, but no randomized trial has compared these 2 strategies for the "hard" clinical end points of death or myocardial infarction nor have earlier studies incorporated the use of coronary stents and aggressive multifaceted medical therapy during long-term follow-up., Methods: The COURAGE trial is a multicenter study of patients with documented myocardial ischemia and angiographically confirmed single or multivessel coronary artery disease who are randomized to a strategy of PCI plus intensive medical therapy or intensive medical therapy alone. Medical therapy in both groups is guideline-driven and includes: aspirin, clopidogrel, simvastatin (low-density lipoprotein cholesterol target 60-85 mg/dL), long-acting metoprolol and/or amlodipine, lisinopril or losartan, and long-acting nitrates, as well as lifestyle interventions. The primary end point is a composite of all-cause mortality or acute myocardial infarction, and there will be 85% power to detect an absolute 4.6% (relative 22%) difference between strategies. The principal hypothesis is that PCI plus aggressive medical therapy (projected event rate 16.4%) will be superior to aggressive medical therapy alone (projected event rate 21%) during a 2.5- to 7-year (median of 5 years) follow-up., Conclusions: COURAGE is the largest prospective randomized trial of PCI versus intensive medical therapy to date and will define the incremental benefits of PCI in the setting of contemporary optimal medical therapy for chronic coronary heart disease. A total of 2287 patients have been enrolled, and follow-up will conclude in June 2006.