Author + information
- Received September 10, 2018
- Revision received November 15, 2018
- Accepted November 26, 2018
- Published online April 22, 2019.
- G.B. John Mancini, MDa,∗ (, )@GBJohnMancini1@UBC,
- David J. Maron, MDb,
- Pamela M. Hartigan, PhDc,
- John A. Spertus, MDd,
- William J. Kostuk, MDe,
- Daniel S. Berman, MDf,
- Koon K. Teo, MBBChg,
- William S. Weintraub, MDh,
- William E. Boden, MDi,
- for the COURAGE Trial Research Group
- aDepartment of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- bDepartment of Medicine, Stanford University, Stanford, California
- cVeterans Affairs Connecticut Healthcare System, West Haven, Connecticut
- dMid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri
- eLondon Health Sciences Centre, University Hospital, London, Ontario, Canada
- fCedars-Sinai Medical Center, Los Angeles, California
- gPopulation Health Research Institute, McMaster University, Hamilton, Ontario, Canada
- hMedStar Heart & Vascular Institute, MedStar Washington Hospital Center, Washington, DC
- iBoston University School of Medicine, VA New England Healthcare System, VA Boston–Jamaica Plain Campus, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. G. B. John Mancini, University of British Columbia, Room 9111, 2775 Laurel Street, Vancouver, British Columbia V5Z 1M9, Canada.
Background The importance of glycosylated hemoglobin A1c (A1c) control as part of comprehensive risk factor management in patients with stable ischemic heart disease (SIHD) and diabetes mellitus (DM) is controversial.
Objectives The purpose of this study was to determine whether a greater number of controlled risk factors at 1 year, including A1c, affects survival in patients with DM and SIHD.
Methods Of 690 patients with DM followed in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 592 (86%) had complete ascertainment of 7 pre-specified risk factors at baseline and after 1 year: systolic blood pressure, low-density lipoprotein cholesterol, nonsmoking, physical activity, diet adherence, body mass index, and A1c. The primary outcome measure was mortality beyond 1 year after randomization.
Results During a mean follow-up of 7.0 ± 4.2 years beyond 1 year after randomization, 186 subjects died (31.4% overall, 4.5%/year). The greater the number of risk factors controlled at 1 year, the higher the probability of survival (unadjusted log rank p = 0.002). Compared with 0 to 1 controlled risk factors, attaining 3 to 7 goals predicted progressively lower mortality (hazard ratio for control of 6 or 7 risk factors was 0.13; 95% confidence interval: 0.05 to 0.40). Importantly, only 10.3% of subjects achieved control of 6 or 7 risk factors. In multivariate analysis, the strongest predictors of improved survival were no smoking, regular physical activity, dietary adherence, and A1c <7%.
Conclusions In this high-risk subset of SIHD patients with DM, the number of controlled risk factors, particularly lifestyle behaviors and A1c, were associated with improved survival. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657)
- guideline-directed medical therapy
- hemoglobin A1c
- optimal medical therapy
- secondary prevention
- stable ischemic heart disease
This study was 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, First Horizon, and GE Healthcare, including in-kind support with U.S. Food and Drug Administration–approved drugs used by study participants. All industrial funding in support of the trial was directed through the U.S. Department of Veterans Affairs. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Dr. Mancini has received honoraria from Regeneron, Merck Canada, Amgen, Sanofi, Boehringer Ingelheim, and AstraZeneca; has served on the Advisory Board for Amgen, Sanofi, Boehringer Ingelheim, and Eli Lilly; and has received grants from Merck Canada, Amgen, Sanofi, Boehringer Ingelheim, and AstraZeneca. Dr. Spertus has served as a consultant to Novartis, Bayer, AstraZeneca, and United Healthcare; has received grant support from Abbott Vascular and Bayer; and has a copyright to the Seattle Angina Questionnaire. Dr. Weintraub has served as a consultant for AstraZeneca, Janssen, and SC Pharma; and has received research funding from Amarin. Dr. Boden has received research funding from Abbvie, Amarin, and Amgen; and has received honoraria from Amarin, Amgen, AstraZeneca, and Janssen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received September 10, 2018.
- Revision received November 15, 2018.
- Accepted November 26, 2018.
- 2019 American College of Cardiology Foundation
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