Anacetrapib
Anacetrapib lipid effects and detectable plasma drug persist for years after stopping treatment (Am J Cardiol 2014)
Original title: Evaluation of lipids, drug concentration, and safety parameters following cessation of treatment with the cholesteryl ester transfer protein inhibitor anacetrapib in patients with or at high risk for coronary heart disease
This study followed 1,398 DEFINE trial patients through a 12-week reversal period after 18 months of anacetrapib treatment, which had previously reduced LDL cholesterol by 39.8% and increased HDL cholesterol by 138.1%. At 12 weeks off study drug, patients previously on anacetrapib still showed placebo-adjusted decreases from baseline in LDL cholesterol (18.6%), non-HDL cholesterol (17.6%), and apolipoprotein B (10.2%), and increases in HDL cholesterol (73.0%) and apolipoprotein A-I (24.5%), alongside residual plasma anacetrapib levels around 40% of on-treatment steady-state trough levels. No clinically important elevations in liver enzymes, blood pressure, or electrolytes occurred during the reversal phase. A small subset (n = 30) still had detectable low concentrations of anacetrapib in plasma 2.5 to 4 years after the last dose, showing that the lipid effects and tissue drug levels of anacetrapib wash out far more slowly than typical small-molecule pharmacokinetics would predict.
Original abstract
The aim of this study was to assess the effects on lipids and safety during a 12-week reversal period after 18 months of treatment with anacetrapib. The cholesteryl ester transfer protein inhibitor anacetrapib was previously shown to reduce low-density lipoprotein cholesterol by 39.8% (estimated using the Friedewald equation) and increase high-density lipoprotein (HDL) cholesterol by 138.1%, with an acceptable side-effect profile, in patients with or at high risk for coronary heart disease in the Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial. A total of 1,398 patients entered the 12-week reversal-phase study, either after completion of the active-treatment phase or after early discontinuation of the study medication. In patients allocated to anacetrapib, placebo-adjusted mean percentage decreases from baseline were observed at 12 weeks off the study drug for Friedewald-calculated low-density lipoprotein cholesterol (18.6%), non-HDL cholesterol (17.6%), and apolipoprotein B (10.2%); placebo-adjusted mean percentage increases were observed for HDL cholesterol (73.0%) and apolipoprotein A-I (24.5%). Residual plasma anacetrapib levels (about 40% of on-treatment apparent steady-state trough levels) were also detected 12 weeks after cessation of anacetrapib. No clinically important elevations in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed during the reversal phase. Preliminary data from a small cohort (n = 30) revealed the presence of low concentrations of anacetrapib in plasma 2.5 to 4 years after the last anacetrapib dose. In conclusion, after the cessation of active treatment, anacetrapib plasma lipid changes and drug levels decreased to approximately 40% of on-treatment trough levels at 12 weeks after dosing, but modest HDL cholesterol elevations and low drug concentrations were still detectable 2 to 4 years after the last dosing.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.