Abstract 15997: The Effect of Combined Statin/Fibrate Therapy on Cardiovascular Disease is Influenced by Sex and Dyslipidemia: ACCORDION-Lipid Long-Term Follow-up
Introduction: In the long-term ACCORD-Lipid trial of 5,518 high risk patients with type 2 diabetes, combined statin+fibrate therapy failed to reduce the composite outcome of nonfatal myocardial infarction (MI), nonfatal stroke or cardiovascular (CV) death. Pre-specified subgroup analyses identified heterogeneity in treatment effect according to gender, with a benefit for men and possible harm for women, and possible benefit for patients with both high triglyceride and low HDL-C at baseline. At trial end, 4,644 ACCORD-Lipid Trial participants consented to be followed post-trial in the passive ACCORD Follow-On (ACCORDION) Study.
Hypothesis: Does a therapeutic strategy that initially used a fibrate to raise HDL-C/lower triglyceride levels and a statin for treatment of LDL-C for a mean of almost 5 years reduce the long-term (mean 9+ years) risk of major CVD events after 4+ more years of follow-up compared to a strategy that only used a statin for treatment of LDL-C?
Results: During about 9 years of follow-up (from ACCORD randomization to the end of ACCORDION), the hazard ratios between participants originally randomized to statin+fibrate versus statin alone were 0.93 (0.83-1.05 95%CI, p=0.25) for the primary outcome (nonfatal MI, nonfatal stroke or CV death); 0.94 (0.84 -1.06, p=0.32) for all-cause mortality, 0.93 (0.78-1.10, p=0.37) for nonfatal MI, and 0.84 (0.69-1.01, p=0.07) for cardiovascular mortality. These hazards are similar to those observed during the trial portion of follow-up. The heterogeneity of response for gender and presence of dyslipidemia observed in ACCORD-LIPID continued to be observed after the addition of post-trial events during the extended follow-up period with hazard ratios of 0.84 (0.73-0.96) for men and 1.30 (1.01-17) for women (interaction P=0.003) and 0.73 (0.56-0.95) for dyslipidemic and 0.99 (0.86-1.13) for non-dyslipidemic subgroups (interaction P=0.048).
Conclusions: Additional post-trial follow-up of ACCORD participants for a total of about 9 years of total follow-up did not alter the original ACCORD findings that in people with type 2 diabetes and other cardiovascular risk factors, long-term treatment with a fibrate+statin (compared to a statin alone) did not reduce the rate of CV events or all-cause mortality.
Author Disclosures: M.B. Elam: Research Grant; Significant; NHLBI. Other Research Support; Significant; Abbott/AbbVie, Merck. L.C. Lovato: None. H.N. Ginsberg: Honoraria; Modest; Sanofi Regeneron, Merck, Amgen, Lilly, BMS, Resverlogix, Cerenis. Consultant/Advisory Board; Modest; Sanofi Regeneron, Merck. Research Grant; Significant; Sanofi Regeneron, Merck, Amgen. Honoraria; Significant; Kowa.
- © 2015 by American Heart Association, Inc.