Abstract 15035: Effects on Lipids and Safety Following Cessation of Treatment with Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib in Patients with or at High Risk for Coronary Heart Disease
The cholesteryl ester transfer protein inhibitor anacetrapib was shown to raise high-density lipoprotein (HDL) cholesterol and reduce low-density lipoprotein (LDL) cholesterol, with an acceptable side-effect profile, in patients with coronary heart disease or at high risk for coronary heart disease in the DEFINE (Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib) trial. The purpose of this study was to assess lipids and safety during a 12-week reversal period after cessation of anacetrapib. 1623 patients on statin therapy entered the 76-week active treatment phase and were randomized to anacetrapib 100 mg daily or placebo. After completion of the active treatment phase (week 76) or upon early discontinuation of the study medication, a total of 1398 patients entered the 12-week reversal phase. Evidence of a persistent drug effect on lipid endpoints was observed after completion of the 12-week reversal period (week 88) in patients allocated to the anacetrapib arm. Persistent placebo-adjusted mean percent reductions from baseline were observed for LDL-C (-18.6%), non-HDL-C (-17.6%), and Apo B (-10.2%), while persistent placebo-adjusted mean percent increases were evident for measures of HDL-C (73.1%) and Apo A-I (24.5%). Sustained placebo-adjusted treatment effects on lipids following the reversal period were approximately 50-60% compared to the active treatment phase results. Residual plasma drug levels were also observed 12 weeks after the cessation of anacetrapib. No patterns of clinically important elevations in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed between the treatment groups. In conclusion, 12 weeks after cessation of active treatment in the DEFINE trial, persistent lipid effects remained in the anacetrapib arm compared to placebo. Cessation of treatment with anacetrapib was well tolerated.
- © 2011 by American Heart Association, Inc.