The class
Schaefer argues CETP inhibitors fail to cut coronary risk because they disrupt normal HDL metabolism (Curr Opin Lipidol 2013)
Original title: Effects of cholesteryl ester transfer protein inhibitors on human lipoprotein metabolism: why have they failed in lowering coronary heart disease risk?
CETP inhibitors block transfer of cholesteryl ester from HDL to triglyceride-rich lipoproteins, raising HDL cholesterol and lowering triglyceride-rich lipoprotein and, in some cases, LDL cholesterol. Dalcetrapib and torcetrapib, tested in large trials of statin-treated coronary heart disease patients, showed no clinical benefit versus placebo, while anacetrapib and evacetrapib were undergoing large trials at the time of writing. Torcetrapib decreased the fractional catabolic rate of HDL apoA-I and apoA-II, increased the fractional catabolic rate of triglyceride-rich lipoprotein apoB-100 and apoE, and decreased triglyceride-rich lipoprotein apoB-48 production, but had no significant effect on fecal cholesterol excretion in humans, and anacetrapib likewise delays HDL apoA-I fractional catabolic rate. The review concludes that CETP inhibitors form complexes with CETP and HDL particles that may interfere with the many normal physiologic functions of HDL, including reverse cholesterol transport, offering a mechanistic explanation for why this drug class has so far failed to reduce coronary heart disease risk.
Original abstract
Purpose Of Review: To examine the recent advances in our knowledge of cholesteryl ester transfer protein (CETP) inhibitors, heart disease risk reduction, and human lipoprotein metabolism.
Recent Findings: CETP inhibitors block the transfer of cholesteryl ester from HDLs to triglyceride-rich lipoproteins (TRLs), thereby raising HDL cholesterol and lowering TRL cholesterol, and in some cases LDL cholesterol. Two CETP inhibitors, dalcetrapib and torcetrapib, have been tested in large clinical trials in statin-treated coronary heart disease patients and have shown no clinical benefit compared to placebo. Anacetrapib and evacetrapib, two potent CETP inhibitors, are now being tested in large clinical trials. Torcetrapib has been shown to decrease the fractional catabolic rate (FCR) of HDL apolipoproteins (apo) A-I and A-II, enhance the FCR of TRL apoB-100 and apoE, and decrease TRL apoB-48 production, but has no significant effects on fecal cholesterol excretion in humans. Anacetrapib also delays the FCR of HDL apoA-I.
Summary: CETP inhibitors form a complex between themselves, CETP, and HDL particles, which may interfere with the many physiologic functions of HDL, including reverse cholesterol transport. Available data would suggest that CETP inhibitors will fail as lipid-altering medications to reduce coronary heart disease risk because of interference with normal human HDL metabolism.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.