Outcomes trials
CETP inhibitor trials show cardiovascular benefit tracks with ApoB reduction rather than HDL-C elevation (Yi Chuan 2026)
Original title: Progress on cholesteryl ester transfer protein-related genes and CETP inhibitor therapy
This narrative review summarises the physiological role of cholesteryl ester transfer protein in atherosclerosis and traces the development of the drug class from the initial HDL-C hypothesis to current clinical understanding. It compares the mechanisms and outcomes of early and contemporary CETP inhibitors, noting that large-scale trials demonstrated HDL-C elevation alone does not guarantee cardiovascular protection. The authors conclude that clinical efficacy aligns more closely with the reduction of ApoB-containing atherogenic lipoprotein burden, framing future research around individualised lipid-lowering strategies and residual risk management.
Original 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.
the classHDL biologyLDL and apoBoutcomes trialspharmacology
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 September 2026. Methods.