Abstract 9649: Lipid-modifying Effects of Anacetrapib in Patients with Lower versus Higher Baseline Levels Of HDL-C, LDL-C, And TG: Pre-Specified Subgroup Analyses of the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) Trial

Abstract

Purpose : Low HDL-C is a risk factor for coronary heart disease which partly accounts for residual risk despite statin therapy. After 24 weeks of treatment, the addition of anacetrapib (ANA), a cholesteryl ester transfer protein (CETP) inhibitor to statin therapy increased HDL-C by 138% and reduced LDL-C by 40% in a 1623 patient safety and lipid efficacy Phase III trial (DEFINE). Sub-group analyses were performed to determine the degree to which ANA raises HDL-C and lowers LDL-C in patients with low baseline HDL-C and in patients with diabetes and other subgroups. Methods: Percent placebo-corrected HDL-C increases and LDL-C decreases from baseline after 24 weeks of ANA, 100 mg/day, were compared among patients according to baseline HDL-C, LDL-C, and TG levels above or below the median and in patients with diabetes. Results: Median baseline HDL-C, LDL-C, and TG were 40 mg/dL, 81 mg/dL, and 128 mg/dL, respectively. ANA produced robust increases in HDL-C in patients with baseline HDL-C below (152%) and above (127%) the median. In the lowest baseline quartile of HDL-C (15 to 34 mg/dL) levels also increased to a mean on-treatment HDL-C of 85 mg/dL. The percent increase in HDL-C was similar in patients with lower vs. higher baseline TG levels. ANA increased HDL-C similarly in diabetics compared to non-diabetics (130% vs 150%) with a mean on-treatment HDL-C of 100 vs. 102 respectively. The percent reduction in LDL-C with ANA was generally similar in patients with lower vs higher baseline LDL-C, HDL-C or TG levels and in patients with or without diabetes. Conclusion: ANA robustly increased HDL-C in all patients especially those with low HDL-C. Reductions in LDL-C with ANA were independent of baseline LDL-C, HDL-C, or TG levels. The clinical impact of these lipid-modifying effects of ANA in these sub-groups will be assessed in REVEAL-HPS3/TIMI55, a 30,000 patient clinical outcomes trial.