The class
A review names failed CETP-inhibitor and niacin trials as key evidence complicating the HDL-cholesterol paradigm for cardiovascular prevention (Clin Pharmacol Ther 2014)
Original title: High-density lipoproteins in the prevention of cardiovascular disease: changing the paradigm
This review reconciles the classic inverse association between HDL cholesterol and cardiovascular events, and the atheroprotective functions of HDL and apolipoprotein A1 shown in animal models such as macrophage cholesterol efflux promotion, vascular inflammation inhibition, and endothelial function enhancement, with recent clinical trials of HDL-cholesterol-raising drugs, including niacin and cholesteryl ester transfer protein (CETP) inhibitors, which have been disappointing. The review examines the current state of the science regarding HDL as a therapeutic target for coronary heart disease, noting that HDL cholesterol has been used as a surrogate measure of HDL function despite the causal nature of the HDL-cardiovascular-risk association being called into question by genetics studies and randomized clinical trials.
Original abstract
High-density-lipoprotein cholesterol (HDL-C) has been identified in population studies as an independent inverse predictor of cardiovascular events. Although the causal nature of this association has been questioned, HDL and its major protein, apolipoprotein (apo)A1, have been shown to prevent and reverse atherosclerosis in animal models. In addition, HDL and apoA1 have several putatively atheroprotective functions, such as the ability to promote efflux of cholesterol from macrophages in the artery wall, inhibit vascular inflammation, and enhance endothelial function. Therefore, HDL-C and apoA1 have been investigated as therapeutic targets for coronary heart disease. However, recent clinical trials with drugs that raise HDL-C, such as niacin and inhibitors of cholesteryl ester transfer protein, have been disappointing. Here, we review the current state of the science regarding HDL as a therapeutic target.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.