Anacetrapib
Were the benefits of REVEAL with anacetrapib really major? A critical evaluation says not significant in years one or two, and modest overall (Expert Opin Pharmacother 2018)
Original title: Cardiovascular outcomes trial with anacetrapib in subjects with high cardiovascular risk - are major benefits REVEALed?
Earlier CETP inhibitors, torcetrapib, dalcetrapib and evacetrapib, raised HDL cholesterol without reducing cardiovascular outcomes in high-risk patients. This evaluation critically assesses the REVEAL trial, in which anacetrapib also inhibited CETP, raised HDL cholesterol and lowered LDL cholesterol. After three years, REVEAL showed cardiovascular benefit with anacetrapib but not a reduction in coronary artery deaths, and the reduction in events was not statistically significant in years one or two individually. In the expert opinion of the author, the benefit of anacetrapib was not major and may not generalise to real-world populations with lower medication adherence than in the trial, and LDL-cholesterol lowering and off-target mechanisms, rather than HDL-cholesterol raising, may explain both the beneficial and any toxic effects. Anacetrapib is noted to have a good safety profile. A sceptical reading of the headline result of REVEAL rather than new trial data.
Original abstract
The actions of the cholesteryl ester transfer protein (CETP) inhibitors (torcetrapib, dalcetrapib and evacetrapib) include increasing high-density lipoprotein (HDL) cholesterol, but they do not reduce cardiovascular outcomes in subjects with high cardiovascular risk. Anacetrapib also inhibits CETP, increases HDL cholesterol and lowers low-density lipoprotein (LDL) cholesterol. Areas covered: This evaluation is of the REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification) trial, which was a cardiovascular outcomes trial with anacetrapib in subjects with high cardiovascular risk. Consideration is given as to whether increasing HDL cholesterol, lowering LDL cholesterol or other mechanisms/factors underlying the positive outcome with this CETP inhibitor. Expert opinion: After three years, the REVEAL trial with anacetrapib, demonstrated cardiovascular benefits, but not a reduction in coronary artery deaths. The reductions were not significant in years one and two. Thus, in my opinion, the benefits of anacetrapib were not major, and may not apply in 'real' world populations where adherence to medicines is lower than in REVEAL. Also, lowering LDL cholesterol and off-target mechanisms of anacetrapib may have contributed to any beneficial and/or toxic effects. Anacetrapib has a good safety profile.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.