Abstract 20114: Effect of Fenofibrate Therapy on Cardiovascular Disease in Men versus Women with Type 2 Diabetes in the ACCORD-Lipid Trial
Background: The ACCORD-Lipid trial assessed effects of combination fenofibrate and simvastatin therapy on cardiovascular disease (CVD) endpoints in Type 2 Diabetes (T2DM). There was no significant reduction in CVD events with combination therapy in ACCORD-Lipid. However, a pre-specified subset analysis showed a significant heterogeneity in response to fenofibrate therapy by sex (P=0.01 for interaction), with men (M) but not women (W) appearing to benefit.
Methods: We examined CVD event rates (MI, stroke, fatal CVD), lipid changes and baseline characteristics among ACCORD-Lipid participants stratified by M (N=3824) and W (N=1694).
Results: The CVD event rate was 13.3% and 11.2% in males treated with placebo or fenofibrate respectively (HR=0.82, 95% CI 0.69-0.99, p=0.04) compared with 6.6% and 9.1% in females (HR=1.38, 95% CI 0.98-1.95, p=0.069). Baseline characteristics in male and female ACCORD-Lipid participants are presented in the table below. Basline HDL-C, LDL-C, Triglyceride, and BMI was higher in women. Women had lower prevalence of prior CVD, white race, peripheral neuropathy, microalbuminuria and lower waist circumference compared to men. Changes in HDL-C and TG in response to fenofibrate treatment were comparable in M vs W (+2.0% vs +2.3% and -43.1% vs -45.9% respectively, p=0.09 and 0.91). LDL-C response to combined fenofibrate-simvastatin treatment was greater in women vs men (-22.6% vs -16.3%, p=0.004).
Conclusions: Despite no effect overall in ACCORD-Lipid, addition of fenofibrate to statin therapy was associated with a 12%, nominally significant lower number of CVD events in M, and a non-statistically significant 38% higher number of CVD events in W. Although W exhibited slightly higher HDL-C, higher frequency of non-white race, and less prior CVD and microvascular disease at baseline than M, it is not clear why W failed to experience reduced CVD event rates with combination lipid therapy. This has not been observed in other fibrate trials.
- © 2010 by American Heart Association, Inc.