Cholesteryl Ester Transfer Protein Inhibition Is Not Yet Dead—Pro. Issue 3 (March 2016)

• Record Type: Journal Article
• Authors: Barter, Philip J.; Rye, Kerry-Anne
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 36:Issue 3(2016)
• Publication Date: 2016-03
• Subjects: atherosclerosis -- cholesterol -- cholesterol-lowering drugs -- cholesterylester transfer protein genetics -- clinical trial -- lipoprotein; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.115.306879
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from nonatherogenic high-density lipoproteins to potentially proatherogenic non–high-density lipoprotein fractions. Human genetic studies and human cohort studies have concluded that CETP gene polymorphisms associated with decreased CETP activity are accompanied by a significantly lower risk of atherosclerotic cardiovascular disease. Inhibition of CETP in rabbits reduces development of diet-induced atherosclerosis. Inhibition of CETP in humans reduces non–high-density lipoprotein cholesterol while increasing high-density lipoproteins cholesterol, consistent with a reduced risk of having an atherosclerotic cardiovascular disease event. The failure of randomized human clinical outcome trials with 3 different CETP inhibitors may have been the consequence of either off-target adverse effects of the drug used or problems with the design of the trials. The hypothesis that CETP inhibition reduces atherosclerotic cardiovascular disease risk is still untested. The future of CETP inhibition as a cardio-protective strategy will depend on the outcome of the ongoing Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial with the CETP inhibitor, anacetrapib.