Frequency, predictors, and consequences of crossing over to revascularization within 12 months of randomization to optimal medical therapy in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial

Abstract

Background: In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, some patients with stable ischemic heart disease randomized to optimal medical therapy (OMT) crossed over to early revascularization. The predictors and outcomes of patients who crossed over from OMT to revascularization are unknown.

Methods and results: We compared characteristics of OMT patients who did and did not undergo revascularization within 12 months and created a Cox regression model to identify predictors of early revascularization. Patients' health status was measured with the Seattle Angina Questionnaire. To quantify the potential consequences of initiating OMT without percutaneous coronary intervention, we compared the outcomes of crossover patients with a matched cohort randomized to immediate percutaneous coronary intervention. Among 1148 patients randomized to OMT, 185 (16.1%) underwent early revascularization. Patient characteristics independently associated with early revascularization were worse baseline Seattle Angina Questionnaire scores and healthcare system. Among 156 OMT patients undergoing early revascularization matched to 156 patients randomized to percutaneous coronary intervention, rates of mortality (hazard ratio=0.51 [0.13-2.1]) and nonfatal myocardial infarction (hazard ratio=1.9 [0.75-4.6]) were similar, as were 1-year Seattle Angina Questionnaire scores. OMT patients, however, experienced worse health status over the initial year of treatment and more unstable angina admissions (hazard ratio=2.8 [1.1-7.5]).

Conclusion: Among COURAGE patients assigned to OMT alone, patients' angina, dissatisfaction with their current treatment, and, to a lesser extent, their health system were associated with early revascularization. Because early crossover was not associated with an increase in irreversible ischemic events or impaired 12-month health status, these findings support an initial trial of OMT in stable ischemic heart disease with close follow-up of the most symptomatic patients.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00007657.

Keywords: angina; chronic coronary artery disease; clinical trials; percutaneous coronary interventions; quality of life.

Conflict of interest statement

Conflicts of Interest: Dr. Spertus discloses that he holds the copyright to the Seattle Angina Questionnaire and has received grant support from NIH, AHA, ACCF, Lilly, and Genentech. He serves as a consultant to United Healthcare, St. Jude Medical and the American Heart Association, where he serves as an Editor for Circulation and Circulation: Cardiovascular Quality and Outcomes. Dr. Cohen discloses that has received research grant support from Boston Scientific, Medtronic and Abbott Vascular and that he has performed consulting services for Medtronic, Cordis and United Healthcare. Dr. Weintraub has received consulting fees from Sanofi-Aventis and Bristol-Myers Squibb and grant support from Sanofi-Aventis. Dr. Berman reports receiving grant support, consulting fees, and lecture fees from Floura Pharma, Bracco Diagnostics, GE Healthcare, Siemens, Lantheus Medical Imaging, and Astellas Healthcare and software royalties from Cedars-Sinai Medical Center. Dr Teo reports receiving lecture and consulting fees and grant support from Boehringer Ingelheim. Dr Shaw reports receiving grant support from Lantheus Imaging and Astellas Healthcare. Dr Boden reports receiving honoraria and lecture fees from Gilead and Sanofi-Aventis and grant support from the National Institutes of Health. Dr Mancini reports receiving consulting fees from Pfizer, AstraZeneca, and GlaxoSmithKline and lecture fees from Merck, AstraZeneca, GlaxoSmithKline, and Sanofi-Aventis. No other potential conflict of interest relevant to this article is reported.

Figures

Figure 1. Timing of Early Revascularization among COURAGE Patients Randomized to Optimal Medical Therapy

Figure 2

Differences in Health Status Over Time Among Matched Patients Treated Initially with PCI and those Treated with OMT Undergoing Early Revascularization: The mean differences among the propensity-matched cohorts in Seattle Angina Questionnaire (SAQ) scores (Black=SAQ Physical Limitation Scale; Red=SAQ Angina Frequency Scale and Blue=SAQ Quality of Life Scale) at each assessment (1, 3, 6 and 12 months) is shown.