Marcin Dada

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

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 ≥10% myocardium. The primary end point was ≥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 ≥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 ≥5% ischemia reduction with OMT with or without coronary revascularization.

Baseline stress myocardial perfusion imaging results and outcomes in patients with stable ischemic heart disease randomized to optimal medical therapy with or without percutaneous coronary intervention

BACKGROUND The COURAGE trial reported similar clinical outcomes for patients with stable ischemic heart disease (SIHD) receiving optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). The current post hoc substudy analysis examined the relationship between baseline stress myocardial ischemia and clinical outcomes based on randomized treatment assignment. METHODS A total of 1,381 randomized patients (OMT n = 699, PCI + OMT n = 682) underwent baseline stress myocardial perfusion single-photon emission computed tomographic imaging. Site investigators interpreted the extent of ischemia by the number of ischemic segments using a 6-segment myocardial model. Patients were divided into those with no to mild (<3 ischemic segments) and moderate to severe ischemia (≥ 3 ischemic segments). Cox proportional hazards models were calculated to assess time to the primary end point of death or myocardial infarction. RESULTS At baseline, moderate to severe ischemia occurred in more than one-quarter of patients (n = 468), and the incidence was comparable in both treatment groups (P = .36). The primary end point, death or myocardial infarction, was similar in the OMT and PCI + OMT treatment groups for no to mild (18% and 19%, P = .92) and moderate to severe ischemia (19% and 22%, P = .53, interaction P value = .65). There was no gradient increase in events for the overall cohort with the extent of ischemia. CONCLUSIONS From the COURAGE trial post hoc substudy, the extent of site-defined ischemia did not predict adverse events and did not alter treatment effectiveness. Currently, evidence supports equipoise as to whether the extent and severity of ischemia impact on therapeutic effectiveness.

Cost-Effectiveness of Percutaneous Coronary Intervention in Optimally Treated Stable Coronary Patients

Background—The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluations) trial compared the effect of percutaneous coronary intervention (PCI) plus optimal medical therapy with optimal medical therapy alone on cardiovascular events in 2287 patients with stable coronary disease. After 4.6 years, there was no difference in the primary end point of death or myocardial infarction, although PCI improved quality of life. The present study evaluated the relative cost and cost-effectiveness of PCI in the COURAGE trial. Methods and Results—Resource use was assessed by diagnosis-related group for hospitalizations and by current procedural terminology code for outpatient visits and tests and then converted to costs by use of 2004 Medicare payments. Medication costs were assessed with the Red Book average wholesale price. Life expectancy beyond the trial was estimated from Framingham survival data. Utilities were assessed by the standard gamble method. The incremental cost-effectiveness ratio was expressed as cost per life-year and cost per quality-adjusted life-year gained. The added cost of PCI was approximately

Predicting Outcome in the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation): Coronary Anatomy Versus Ischemia

10 000, without significant gain in life-years or quality-adjusted life-years. The incremental cost-effectiveness ratio varied from just over

Effect of PCI on Long-Term Survival in Patients with Stable Ischemic Heart Disease

168 000 to just under

Intensive Multifactorial Intervention for Stable Coronary Artery Disease Optimal Medical Therapy in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) Trial

300 000 per life-year or quality-adjusted life-year gained with PCI. A large minority of the distributions found that medical therapy alone offered better outcome at lower cost. The costs per patient for a significant improvement in angina frequency, physical limitation, and quality of life were

Optimal medical therapy with or without percutaneous coronary intervention for patients with stable coronary artery disease and chronic kidney disease.

154 580,

Impact of Optimal Medical Therapy With or Without Percutaneous Coronary Intervention on Long-Term Cardiovascular End Points in Patients With Stable Coronary Artery Disease (from the COURAGE Trial)

112 876, and

Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: A post-hoc analysis from the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation).

124 233, respectively. Conclusions—The COURAGE trial did not find the addition of PCI to optimal medical therapy to be a cost-effective initial management strategy for symptomatic, chronic coronary artery disease.

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.

OBJECTIVES The aim of this study was to determine the relative utility of anatomic and ischemic burden of coronary artery disease for predicting outcomes. BACKGROUND Both anatomic burden and ischemic burden of coronary artery disease determine patient prognosis and influence myocardial revascularization decisions. When both measures are available, their relative utility for prognostication and management choice is controversial. METHODS A total of 621 patients enrolled in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial with baseline quantitative nuclear single-photon emission computed tomography (SPECT) and quantitative coronary angiography were studied. Several multiple regression models were constructed to determine independent predictors of the endpoint of death, myocardial infarction (MI) (excluding periprocedural MI) and non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Ischemic burden during stress SPECT, anatomic burden derived from angiography, left ventricular ejection fraction, and assignment to either optimal medical therapy (OMT) + percutaneous coronary intervention (PCI) or OMT alone were analyzed. RESULTS In nonadjusted and adjusted regression models, anatomic burden and left ventricular ejection fraction were consistent predictors of death, MI, and NSTE-ACS, whereas ischemic burden and treatment assignment were not. There was a marginal (p = 0.03) effect of the interaction term of anatomic and ischemic burden for the prediction of clinical outcome, but separately or in combination, neither anatomy nor ischemia interacted with therapeutic strategy to predict outcome. CONCLUSIONS In a cohort of patients treated with OMT, anatomic burden was a consistent predictor of death, MI, and NSTE-ACS, whereas ischemic burden was not. Importantly, neither determination, even in combination, identified a patient profile benefiting preferentially from an invasive therapeutic strategy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).