Outcomes trials
Review tallies the HDL-C and LDL-C effects of each CETP inhibitor ahead of anacetrapib and evacetrapib outcomes in 2017 (Curr Pharm Des 2013)
Original title: The promise of cholesteryl ester transfer protein (CETP) inhibition in the treatment of cardiovascular disease
This review discusses the role of HDL cholesterol (HDL-C) in atherogenesis and the promise of cholesteryl ester transfer protein (CETP) inhibition for cardiovascular disease prevention beyond statins. CETP inhibition reliably raises HDL-C in humans, but the first CETP inhibitor tested in phase III trials, torcetrapib, increased mortality, likely from vasopressor effects specific to that compound. Dalcetrapib subsequently raised HDL-C by 30% without any effect on cardiovascular outcomes, challenging the HDL-C hypothesis, while anacetrapib and evacetrapib, then in phase III trials, had shown no adverse effects and increased HDL-C by 129% to 151% and decreased LDL-C by 36% to 41%, with anacetrapib also lowering lipoprotein(a) by 17%. The authors anticipate these combined lipid effects will reduce cardiovascular risk, with results expected in 2017.
Original abstract
There is a strong need to reduce the risk of cardiovascular disease (CVD) beyond the use of statins that lower low-density lipoprotein cholesterol (LDL-C). The inverse relationship of high-density lipoprotein cholesterol (HDL-C) with cardiovascular disease suggests HDL-C raising therapy as a novel target. This review discusses the role of HDL-C in atherogenesis as well as the promise of cholesteryl ester transfer protein (CETP) inhibition in CVD prevention. While genetic studies show conflicting results on correlations between HDL-C and CVD, experimental studies have yielded sufficient encouraging data to proceed with the development of HDL-C raising strategies. CETP inhibition has been shown to successfully increase HDL-C levels in man. However, the first CETP inhibitor tested in phase III trials increased mortality possibly due to torcetrapib-specific vasopressor effects. More recently, dalcetrapib did not show an effect on CVD outcome while raising HDL-C by 30%, thereby refuting the HDL-C hypothesis. Anacetrapib and evacetrapib are currently tested in phase III clinical trials and have not shown adverse effects thus far. Both compounds not only increase HDL-C by 129-151%, they also decrease LDL-C (36-41%) and anacetrapib lowers Lp(a) (17%). Combined, these effects are anticipated to decrease CVD risk and the results will be revealed in 2017.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.