Cardiovascular outcomes trial with anacetrapib in subjects with high cardiovascular risk - are major benefits REVEALed?

Introduction : 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.