title: Cholesteryl ester transfer protein inhibition to reduce cardiovascular risk: Where are we now?
abstract: Elevated low-density lipoprotein-cholesterol (LDL-C) and reduced high-density lipoprotein-cholesterol (HDL-C) are major risk factors for the development of cardiovascular disease. One approach to raising HDL-C is to inhibit the cholesteryl ester transfer protein (CETP), a plasma protein that promotes transfer of cholesteryl esters from HDL and other lipoprotein fractions. Drugs that inhibit CETP increase HDL-C and some lower LDL-C. However, the development of torcetrapib, the first CETP inhibitor to be tested in a human clinical outcomes trial, was terminated because it caused an excess of deaths and cardiovascular events. There is evidence, however, that torcetrapib had adverse off-target effects unrelated to CETP inhibition. This has opened the way for retesting of the hypothesis that CETP inhibitors will be anti-atherogenic in studies conducted with agents such as dalcetrapib and anacetrapib that do not share the off-target effects of torcetrapib. Clinical outcome trials with dalcetrapib and anacetrapib are currently under way.
authors.affiliation: The Heart Research Institute, 7 Eliza Street, Newtown, Sydney 2042, Australia. barterp@hri.org.au
authors.forename: Philip
authors.initials: P
authors.lastname: Barter
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D000577:Amides; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D053480:Cholesterol Ester Transfer Proteins / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004952:Esters; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use; D012306:Risk; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000577:Amides; D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D004952:Esters; D023303:Oxazolidinones; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; C530884:anacetrapib