Do Cholesteryl Ester Transfer Protein Inhibitors Have a Role in the Treatment of Cardiovascular Disease?
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Cholesteryl ester transfer protein (CETP) plays an important role in lipid metabolism and has presented an attractive target for drug development, primarily resting on the hope that CETP inhibition would reduce cardiovascular events through its ability to increase levels of high-density lipoprotein cholesterol (HDL-C). However, clinical development of CETP inhibitors has proven disappointing, with a spectrum of results spanning from evidence of harm, to futility, to only modest benefit in large-scale cardiovascular outcomes trials. A number of additional insights from genomic studies have suggested potential benefits from these agents in specific clinical settings. We review the current state of CETP inhibitors as an approach to targeting cardiovascular risk.
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No external funds were used to prepare this manuscript.
Conflict of interest
SJN has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, Novartis, InfraReDx, and Sanofi-Regeneron and is a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi-Regeneron and Novo Nordisk. AJN has no conflicts of interest that are directly relevant to the content of this article.
- 21.Nicholls SJ, Tuzcu EM, Brennan DM, Tardif JC, Nissen SE. Cholesteryl ester transfer protein inhibition, high-density lipoprotein raising, and progression of coronary atherosclerosis: insights from ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation). Circulation. 2008;118(24):2506–14.CrossRefGoogle Scholar
- 32.Bloomfield D, Carlson GL, Sapre A, Tribble D, McKenney JM, Littlejohn TW 3rd, et al. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am Heart J. 2009;157(2):352–360 e2.CrossRefGoogle Scholar
- 40.Brousseau ME, O’Connor JJ Jr, Ordovas JM, Collins D, Otvos JD, Massov T, et al. Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency: Veterans Affairs HDL Cholesterol Intervention Trial. Arterioscler Thromb Vasc Biol. 2002;22(7):1148–54.CrossRefGoogle Scholar
- 41.Ridker PM, Pare G, Parker AN, Zee RY, Miletich JP, Chasman DI. Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: genomewide analysis among 18,245 initially healthy women from the Women’s Genome Health Study. Circ Cardiovasc Genet. 2009;2(1):26–33.CrossRefGoogle Scholar
- 46.Barter PJ, Rye KA, Tardif JC, Waters DD, Boekholdt SM, Breazna A, et al. Effect of torcetrapib on glucose, insulin, and hemoglobin A1c in subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial. Circulation. 2011;124(5):555–62.CrossRefGoogle Scholar