Abstract:

Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high-density lipoprotein (HDL) to apolipoprotein B (ApoB)-containing lipoproteins. Inhibition of CETP can increase high-density lipoprotein cholesterol (HDL-C) while reducing low-density lipoprotein cholesterol (LDL-C). Early epidemiological studies proposed the hypothesis that “raising HDL-C confers cardiovascular protection”, which greatly promoted the development of CETP inhibitors. However, results from multiple large-scale clinical trials in recent years have shown that simply increasing HDL-C does not consistently translate into cardiovascular benefits. Instead, the therapeutic effects may be more closely related to the reduction of ApoB-containing atherogenic lipoprotein burden. Here, we systematically summarize the physiological functions of CETP and its role in the development and progression of atherosclerosis, review the development history and major clinical trial outcomes of CETP inhibitors, compare the differences among various agents in reducing ApoB-containing lipoproteins and improving clinical outcomes, and discuss the future prospects and research challenges of this drug class, with the aim of providing references for individualized lipid-lowering therapy in atherosclerotic cardiovascular disease.

Key words: cholesteryl ester transfer protein (CETP), CETP inhibitors, HDL-C, LDL-C, atherosclerotic cardiovascular disease