Outcomes trials
CETP inhibition is not yet dead, argues a pro perspective ahead of the REVEAL trial (Arterioscler Thromb Vasc Biol 2016)
Original title: Cholesteryl Ester Transfer Protein Inhibition Is Not Yet Dead--Pro
In a paired perspective piece, Barter and Rye argue that cholesteryl ester transfer protein (CETP) inhibition remains a viable cardioprotective strategy despite earlier trial failures. They note that human genetic and cohort studies link CETP polymorphisms associated with lower CETP activity to significantly lower cardiovascular risk, that CETP inhibition reduces diet-induced atherosclerosis in rabbits, and that inhibiting CETP in humans lowers non-HDL cholesterol while raising HDL cholesterol. The authors argue the failure of three prior CETP inhibitor outcome trials may reflect off-target drug effects or trial design issues rather than a flawed hypothesis, and that the question remains genuinely untested pending results of the ongoing REVEAL trial with anacetrapib.
Original abstract
Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from nonatherogenic high-density lipoproteins to potentially proatherogenic non-high-density lipoprotein fractions. Human genetic studies and human cohort studies have concluded that CETP gene polymorphisms associated with decreased CETP activity are accompanied by a significantly lower risk of atherosclerotic cardiovascular disease. Inhibition of CETP in rabbits reduces development of diet-induced atherosclerosis. Inhibition of CETP in humans reduces non-high-density lipoprotein cholesterol while increasing high-density lipoproteins cholesterol, consistent with a reduced risk of having an atherosclerotic cardiovascular disease event. The failure of randomized human clinical outcome trials with 3 different CETP inhibitors may have been the consequence of either off-target adverse effects of the drug used or problems with the design of the trials. The hypothesis that CETP inhibition reduces atherosclerotic cardiovascular disease risk is still untested. The future of CETP inhibition as a cardio-protective strategy will depend on the outcome of the ongoing Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial with the CETP inhibitor, anacetrapib.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.