The class
Chapman and colleagues place CETP at the center of how statins, fibrates, niacin, and CETP inhibitors modulate HDL (Eur Heart J 2010)
Original title: Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors
This review examines cholesteryl ester transfer protein (CETP) as a central modulator not only of HDL and apolipoprotein A-I metabolism but also of triglyceride-rich particles and LDL, transferring cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins while moving triglycerides mainly from VLDL to HDL. CETP activity is elevated in insulin-resistant, hypertriglyceridemic dyslipidemia and is closely tied to premature atherosclerosis and cardiovascular risk, making CETP inhibition an attractive strategy for raising HDL-C. The authors appraise evidence that statins, fibrates, and niacin act partly through effects on CETP, and compare these mechanisms with those of CETP inhibitors then in development, including dalcetrapib and anacetrapib, designed to directly normalize HDL/apoA-I levels and HDL antiatherogenic activity. The authors conclude that ongoing long-term, large-scale outcome trials of these CETP inhibitors are essential to establish their safety and efficacy for reducing residual cardiovascular risk.
Original abstract
Subnormal plasma levels of high-density lipoprotein cholesterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. Cholesteryl ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. Cholesteryl ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. Cholesteryl ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.