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

• Type of Material: Article
• Authors: John A Spertus, University of Missouri; David J Maron, Vanderbilt University; David Cohen, Emory University; Paul Kolm, Christiana Care Health System; Pam Hartigan, VA Connecticut Healthcare Center; William Seth Weintraub, Emory University; Daniel S. Berman, Cedars-Sinai Medical Center; Robert O'Rourke, Audie Murphy VAMC; Koon K Teo, McMaster University; Leslee Shaw, Emory University; Steven Sedlis, New York VA Medical Center; Merril Knudtson, Libin Cardiovascular Institute; Mihaela Aslan, VA Connecticut Healthcare Center; Marcin Dada, Hartford Hospital; William E. Boden, State University of New York Buffalo; G. B. John Mancini, University of British Columbia
• Language: English
• Date: 2013-07-01
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 American Heart Association, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1161/CIRCOUTCOMES.113.000139
• Title of Journal or Parent Work: Circulation: Cardiovascular Quality and Outcomes
• ISSN: 1941-7705
• Volume: 6
• Issue: 4
• Start Page: 409
• End Page: 418
• Grant/Funding Information: All industrial funding in support of the trial was directed through the U.S. Department of Veterans Affairs.; Supported by the Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development, in collaboration with the Canadian Institutes of Health Research; and by unrestricted research grants from Merck, Pfizer, Bristol- Myers Squibb, Fujisawa, Kos Pharmaceuticals, Datascope, AstraZeneca, Key Pharmaceutical, Sanofi-Aventis, First Horizon, and GE Healthcare; including in-kind support with FDA-approved drugs used by study participants.
• Keywords: Science & Technology; ASSOCIATION TASK-FORCE; CHRONIC STABLE ANGINA; percutaneous coronary interventions; ACUTE MYOCARDIAL-INFARCTION; Cardiac & Cardiovascular Systems; angina; HEART-ASSOCIATION; Life Sciences & Biomedicine; chronic coronary artery disease; PERCUTANEOUS CORONARY INTERVENTION; QUALITY-OF-LIFE; AMERICAN-COLLEGE; clinical trials; Cardiovascular System & Cardiology; ARTERY-DISEASE; PRACTICE GUIDELINES COMMITTEE; quality of life; UNITED-STATES
• Research Categories: Health Sciences, Medicine and Surgery

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.