Outcomes of Combined Cardiovascular Risk Factor Management Strategies in Type 2 Diabetes: The ACCORD Randomized Trial

• Type of Material: Article
• Authors: Karen L. Margolis, HealthPartners Institute for Education and Research; Patrick J. O'Connor, HealthPartners Institute for Education and Research; Timothy M. Morgan, Wake Forest University; John B. Buse, University of North Carolina; Robert M. Cohen, University of Cincinnati; William C. Cushman, Memphis Veterans Affairs Medical Center; Jeffrey A. Cutler, National Heart, Lung, and Blood Institute; Gregory W. Evans, Wake Forest University; Hertzel C. Gerstein, McMaster University; Richard H. Grimm, Jr., Berman Center for Outcomes and Clinical Research; Edward W. Lipkin, University of Washington; K.M. Venkat Narayan, Emory University; Matthew C. Riddle, Oregon Health and Science University; Ajay Sood, Case Western Reserve University; David C. Goff, Jr., Colorado School of Public Health
• Language: English
• Date: 2014-06-01
• Publisher: AMER DIABETES ASSOC
• Publication Version: Final Published Version
• Copyright Statement: © 2014 by the American Diabetes Association.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.2337/dc13-2334
• Title of Journal or Parent Work: DIABETES CARE
• Volume: 37
• Issue: 6
• Start Page: 1721
• End Page: 1728
• Grant/Funding Information: This work was supported by the NHLBI (contracts N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC-1010) and partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute and by General Clinical Research Centers at many sites.; K.L.M. has NIH studies with funds going to her institution and assumes all responsibility for the work as a whole.; All authors were supported by NIH grant funds for the ACCORD trial during the study.; The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceuticals, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi, and Schering-Plough.; Substudies within the ACCORD trial on cost-effectiveness and health-related quality of life were supported by the Centers for Disease Control and Prevention.; W.C.C. reports grants from NHLBI and NIH during the conduct of the study.
• Keywords: DESIGN; Science & Technology; Endocrinology & Metabolism; TARGETS; MULTIFACTORIAL INTERVENTION; Life Sciences & Biomedicine; MICROVASCULAR OUTCOMES; INTENSIVE BLOOD-PRESSURE; MORTALITY; THERAPY; RATIONALE; DISEASE; MELLITUS
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

OBJECTIVE To compare effects of combinations of standard and intensive treatment of glycemia and either blood pressure (BP) or lipids in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS ACCORD enrolled 10,251 type 2 diabetes patients aged 40–79 years at high risk for cardiovascular disease (CVD) events. Participants were randomly assigned to hemoglobin A1c goals of <6.0% (<42 mmol/mol; intensive glycemia) or 7.0–7.9% (53–63 mmol/mol; standard glycemia) and then randomized a second time to either 1) systolic BP goals of <120 mmHg (intensive BP) or <140 mmHg (standard BP) or 2) simvastatin plus fenofibrate (intensive lipid) or simvastatin plus placebo (standard lipid). Proportional hazards models were used to assess combinations of treatment assignments on the composite primary (deaths due to CVD, nonfatal myocardial infarction [MI], and nonfatal stroke) and secondary outcomes. RESULTS In the BP trial, risk of the primary outcome was lower in the groups intensively treated for glycemia (hazard ratio [HR] 0.67; 95% CI 0.50–0.91), BP (HR 0.74; 95% CI 0.55–1.00), or both (HR 0.71; 95% CI 0.52–0.96) compared with combined standard BP and glycemia treatment. For secondary outcomes, MI was significantly reduced by intensive glycemia treatment and stroke by intensive BP treatment; most other HRs were neutral or favored intensive treatment groups. In the lipid trial, the general pattern of results showed no evidence of benefit of intensive regimens (whether single or combined) compared with combined standard lipid and glycemia treatment. The mortality HR was 1.33 (95% CI 1.02–1.74) in the standard lipid/intensive glycemia group compared with the standard lipid/standard glycemia group. CONCLUSIONS In the ACCORD BP trial, compared with combined standard treatment, intensive BP or intensive glycemia treatment alone improved major CVD outcomes, without additional benefit from combining the two. In the ACCORD lipid trial, neither intensive lipid nor glycemia treatment produced an overall benefit, but intensive glycemia treatment increased mortality.