Inhibition of CETP as a novel therapeutic strategy for reducing the risk of atherosclerotic disease.
Lowering low-density lipoprotein cholesterol (LDL-C) levels with statins is a proven strategy for reducing the risk of atherothrombotic cardiovascular disease (CVD). Yet, despite the success of statins in reducing cardiovascular event rates in at-risk patients, many will still experience further events. There is, therefore, a need to develop suitable therapies to reduce this residual risk. Low high-density lipoprotein cholesterol (HDL-C) levels are an important independent risk factor for CVD. Though fibrates, niacin, and statins have been shown to modestly raise HDL-C, there is increasing recognition of the need to develop therapies that can increase HDL-C more robustly. Such therapies may help supplement the LDL-C-lowering benefits of statins. Inhibition of cholesteryl ester transfer protein (CETP) has been identified as a possible strategy for substantially increasing HDL-C levels and CETP inhibitors have demonstrated clinical efficacy, in terms of increasing HDL-C, in preliminary clinical trials, and clinical trials based on outcomes are ongoing. Two CETP inhibitors, JTT-705 and torcetrapib, are now being evaluated more extensively.
Shah
Prediman K
PK
Division of Cardiology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. shahp@cshs.org
D000577:Amides; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004952:Esters; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D009154:Mutation / Q000235:genetics; D012307:Risk Factors; D013438:Sulfhydryl Compounds / Q000627:therapeutic use
D000577:Amides; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D004952:Esters; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; D002784:Cholesterol