Abstract 19724: Hypertriglyceridemia and Low HDL-C Predicts Fenofibrate Response in The ACCORD-Lipid Trial
Background: The ACCORD-Lipid trial assessed effects of combination fenofibrate and simvastatin therapy on cardiovascular disease (CVD) in Type 2 Diabetes (T2DM). CVD events were not significantly reduced with combination therapy in the entire cohort. A prespecified analysis identified an ACCORD subgroup with baseline triglyceride ≥ 204 mg/dl and HDL-C ≤ 34 mg/dl (HTG/LHDL) in whom there was a suggestion of heterogeneity in their response to combination therapy vs. all other participants (interaction p=0.057). The purpose of this post-hoc analysis is to identify characteristics of this subgroup that distinguish it from the remainder of the cohort.
Methods: We examined lipid changes CVD events, and baseline characteristics of ACCORD-Lipid participants with HTG/LHDL (N=941) at baseline versus the other 4548 ACCORD-Lipid participants.
Results: The CVD event rate in the HTG/LHDL subgroup was 12.4% in those treated with combination therapy versus 17.3% in those receiving simvastatin alone (HR=0.69, 95% CI 0.49 - 0.97, p=0.03); the CVD event rate in all other participants was 10.1% in both treatment groups. The mean baseline HDL-C in the HTG/LHDL subgroup (N= 941) was 29.5 ± 3.7 and median TG was 285 mg/dl. Mean LDL-C was 97.3 + 32.5 mg/dl. Members of the HTG/LDHL subgroup were more likely to be male (80% vs 68.1%), white (80% vs 68.5%), and to have had a history of prior CVD (40.5% vs 35.7%). Members of the HTG/LHDL subgroup were also more likely to have microvascular disease at baseline, including peripheral neuropathy (48.8% vs 44.6%) , macroalbuminuria (7.7% vs 6.9%), and microalbuminuria (36.8% vs 29.2%). There were no differences in duration of diabetes or median HbA1c between the two groups. The HTG/LHDL subgroup responded to fenofibrate therapy with greater increase in HDL-C (+4.5 vs +1.6 mg/dl; p=<0.0001) and greater decrease in median TG (-122.5 vs -25.0 mg/dl; p =<0.0001) after 48 months of treatment.
Conclusions: Despite no effect overall in ACCORD-Lipid, a prespecified subgroup of ACCORD-Lipid participants with baseline TG ≥ 204 mg/dl and HDL-C ≤ 34 mg/dl may have experienced fewer CVD events following treatment with combination fenofibrate-simvastatin therapy. This group is also characterized by a higher prevalence of males, white race, and prior CVD.
- © 2010 by American Heart Association, Inc.