The class
Review argues the time is right to test CETP inhibition in randomized human atherosclerosis trials (Arterioscler Thromb Vasc Biol 2003)
Original title: Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis
This review lays out the case for CETP as a novel HDL-raising, atherosclerosis-inhibiting target. It notes CETP inhibition retards atherogenesis in rabbits, a species with naturally high CETP, while mouse studies (a species lacking CETP activity) have given mixed results, and that humans with heterozygous CETP deficiency and HDL cholesterol above 60 mg/dL have reduced coronary heart disease risk, though evidence of increased atherosclerosis in CETP-deficient subjects without raised HDL is harder to interpret. Small-molecule CETP inhibitors had by then been tested in humans and shown to raise HDL cholesterol while lowering LDL cholesterol and apoB, leading the authors to argue it was important and timely to test in randomized human trials whether pharmacological CETP inhibition actually retards atherosclerosis.
Original abstract
Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from antiatherogenic HDLs to proatherogenic apolipoprotein B (apoB)-containing lipoproteins, including VLDLs, VLDL remnants, IDLs, and LDLs. A deficiency of CETP is associated with increased HDL levels and decreased LDL levels, a profile that is typically antiatherogenic. Studies in rabbits, a species with naturally high levels of CETP, support the therapeutic potential of CETP inhibition as an approach to retarding atherogenesis. Studies in mice, a species that lacks CETP activity, have provided mixed results. Human subjects with heterozygous CETP deficiency and an HDL cholesterol level >60 mg/dL have a reduced risk of coronary heart disease. Evidence that atherosclerosis may be increased in CETP-deficient subjects whose HDL levels are not increased is difficult to interpret and may reflect confounding or bias. Small-molecule inhibitors of CETP have now been tested in human subjects and shown to increase the concentration of HDL cholesterol while decreasing that of LDL cholesterol and apoB. Thus, it seems important and timely to test the hypothesis in randomized trials of humans that pharmacological inhibition of CETP retards the development of atherosclerosis.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.