Effects of anacetrapib on plasma lipids in specific patient subgroups in the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) trial

•Anacetrapib is an orally active, potent, selective inhibitor of CETP.•DEFINE showed robust lipid effects of anacetrapib + statin in CHD patients.•Lipid effects of anacetrapib across subgroups of DEFINE patients are reported.•Lipid effects of anacetrapib were generally comparable across subgroups.

BackgroundIn the Determining the Efficacy and Tolerability of cholesteryl ester transfer protein (CETP) INhibition with AnacEtrapib (DEFINE) trial, anacetrapib added to statin produced robust low-density lipoprotein cholesterol (LDL-C)-lowering and high-density lipoprotein cholesterol (HDL-C)-raising vs placebo in patients with coronary heart disease (CHD). Predictors of the degree of LDL-C and HDL-C responses to anacetrapib, however, are poorly understood.ObjectiveLipid effects of anacetrapib in patient subgroups within the DEFINE trial (clinicaltrials.gov: NCT00685776) are reported.MethodsThe percent of placebo-corrected changes from baseline for LDL-C (estimated by Friedewald calculation [Fc-LDL-C]) and HDL-C after 24 weeks of anacetrapib 100 mg/day were compared among patients by age, gender, race, diabetes status, type of concomitant statin with or without other lipid therapies, and baseline HDL-C, Fc-LDL-C, and triglyceride (TG) levels.ResultsPercent decreases in Fc-LDL-C and increases in HDL-C with anacetrapib were similar (magnitude of difference generally <1/5 of the overall treatment effect) across subgroups by age, gender, diabetes status, lipid-modifying regimen, and baseline Fc-LDL-C, HDL-C, or TG. On the other hand, anacetrapib effects on Fc-LDL-C (−24% vs −41%) and HDL-C (+75% vs +139%) appeared to be less in black vs white patients, respectively.ConclusionEffects of anacetrapib on Fc-LDL-C and HDL-C were generally comparable across subgroups, including being relatively independent of baseline Fc-LDL-C, HDL-C, or TG levels. The clinical impact of the lipid-modifying effects of anacetrapib is being evaluated in the cardiovascular disease outcomes trial, Randomized EValuation of the Effects of Anacetrapib though Lipid-modification (REVEAL).