Torcetrapib
A review says the CETP crystal structure could enable inhibitors that avoid the nonproductive HDL-binding complex formed by torcetrapib (Curr Opin Cardiol 2007)
Original title: Where are we with high-density lipoprotein raising and inhibition of cholesteryl ester transfer for heart disease risk reduction?
This review examines recent research on raising HDL cholesterol via CETP inhibition for coronary heart disease risk reduction. CETP inhibitors prevent transfer of cholesteryl ester from HDL to triglyceride-rich lipoproteins; torcetrapib, one such inhibitor, binds to CETP on HDL and markedly raises HDL cholesteryl ester with no effect on fecal cholesterol excretion, but can raise blood pressure. A large clinical trial in coronary heart disease patients on atorvastatin was recently stopped early because of excess mortality with torcetrapib versus placebo, and two other trials reported no benefit on coronary atherosclerosis or carotid intimal medial thickness compared with atorvastatin alone. The authors argue the adverse effects of torcetrapib may be compound specific, and since the crystal structure of CETP is now known, more optimal CETP inhibitors could be developed that avoid forming the nonproductive complex with CETP on HDL particles reported for torcetrapib, alongside continued development of better-tolerated niacin preparations.
Original abstract
Purpose Of Review: To review recent research in the area of high-density lipoprotein raising and coronary heart disease risk reduction.
Recent Findings: A decreased high-density lipoprotein-cholesterol is an important coronary heart disease risk factor and raising high-density lipoprotein-cholesterol has been associated with coronary heart disease risk reduction. A relative new strategy for raising high-density lipoprotein-cholesterol, i.e. inhibition of cholesteryl ester transfer protein, is markedly effective. Cholesteryl ester transfer protein inhibitors prevent the transfer of cholesteryl ester from high-density lipoprotein to triglyceride-rich lipoproteins in exchange for triglyceride. One inhibitor, torcetrapib, binds to cholesteryl ester transfer protein on high-density lipoprotein, markedly raises high-density lipoprotein-cholesteryl ester and has no effect on fecal cholesterol excretion, but can raise blood pressure. A large clinical trial in coronary heart disease patients on atorvastatin was recently stopped prematurely because of excess mortality in those receiving torcetrapib vs. placebo and two other trials reported no benefit of torcetrapib on coronary atherosclerosis or carotid artery intimal medial thickness as compared with subjects on atorvastatin alone.
Summary: The adverse effects of torcetrapib may be compound-specific and, since the crystal structure of cholesteryl ester transfer protein is now known, it should be possible to develop more optimal cholesteryl ester transfer protein inhibitors that do not form a nonproductive complex with cholesteryl ester transfer protein on the high-density lipoprotein particle, as has been reported for torcetrapib. The alternative for high-density lipoprotein raising is to develop more effective and better tolerated niacin preparations.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.