The class
Review questions whether HDL cholesterol is a modifiable treatment target after disappointing CETP inhibitor trials (JRSM Cardiovasc Dis 2019)
Original title: Is high-density lipoprotein a modifiable treatment target or just a biomarker for cardiovascular disease?
This review examines three decades of pharmaceutical strategies aimed at raising HDL cholesterol against the strong epidemiological link between low HDL-C and cardiovascular risk. It focuses on cholesteryl ester transfer protein (CETP) inhibitors, a drug class that raises circulating HDL-C by blocking the exchange of cholesteryl ester from HDL for triacylglycerol in larger lipoproteins such as VLDL and LDL. Despite this pharmacological success in raising HDL-C, recent trials of CETP inhibitors have not shown clinical benefit. The author discusses the evidence linking HDL-C to cardiovascular risk and the implications of these disappointing CETP inhibitor trial results for whether HDL-C itself is a valid modifiable treatment target or merely a biomarker.
Original abstract
Epidemiological data strongly support the inverse association between high-density lipoprotein cholesterol concentration and cardiovascular risk. Over the last three decades, pharmaceutical strategies have been partially successful in raising high-density lipoprotein cholesterol concentration, but clinical outcomes have been disappointing. A recent therapeutic class is the cholesteryl ester transfer protein inhibitor. These drugs can increase circulating high-density lipoprotein cholesterol levels by inhibiting the exchange of cholesteryl ester from high-density lipoprotein for triacylglycerol in larger lipoproteins, such as very low-density lipoprotein and low-density lipoprotein. Recent trials of these agents have not shown clinical benefit. This article will review the evidence for cardiovascular risk associated with high-density lipoprotein cholesterol and discuss the implications of the trial data for cholesteryl ester transfer protein inhibitors.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.