Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus

By H. Ginsberg, M. Elam, L. Lovato, J. Crouse, Lawrence A Leiter, P. Linz, W. Friedewald, John B. Buse, H. Gerstein, J. Probstfield and 7 more. New England Journal of Medicine, 2010

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BACKGROUND We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease. METHODS We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. RESULTS The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P = 0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P = 0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P = 0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P = 0.057 for interaction). CONCLUSIONS The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

Subfields: Endocrinology, Diabetes and Metabolism, Surgery

View Paper: https://www.semanticscholar.org/paper/4cc5c0f4a6be20b153f22c2a1571f2234644503a

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In Endocrinology, Diabetes and Metabolism

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Citations in the corpus

Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes – Mechanisms, Management, and Clinical Considerations (2016, positive): “Inclusion in the ACCORD-Lipid substudy did not require high triglyceride and low HDL cholesterol levels, a group which might benefit most from fibrate therapy.(210) Although there was no difference in the annual rate of the primary composite outcome of major adverse cardiovascular events (nonfatal m”
CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY. (2016, background): “The addition of fenofibrate to statins in the ACCORD study showed no benefit in the overall cohort in which mean baseline triglycerides and HDL-C were within normal limits (204).”
Metabolic syndrome update. (2016, background): “In another RCT in patients with diabetes, adding fenofibrate to statin therapy found no benefit [96]; but in a subgroup with hypertriglyceridemia, a nearly significant decrease in risk (p 1⁄4 0.”
Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management (2011, background): “those without this profile).(106,107) Analyses from FIELD”
Dyslipidemia in Obesity: Mechanisms and Potential Targets (2013, background): “However, there is controversy about the effectiveness of fibrate therapy on top of statin therapy since the ACCORD trial was unable to confirm a beneficial effect on cardiovascular endpoints by fenofibrate combined with statins in diabetic patients [156].”