title: The promise of cholesteryl ester transfer protein (CETP) inhibition in the treatment of cardiovascular disease.
abstract: There is a strong need to reduce the risk of cardiovascular disease (CVD) beyond the use of statins that lower low-density lipoprotein cholesterol (LDL-C). The inverse relationship of high-density lipoprotein cholesterol (HDL-C) with cardiovascular disease suggests HDL-C raising therapy as a novel target. This review discusses the role of HDL-C in atherogenesis as well as the promise of cholesteryl ester transfer protein (CETP) inhibition in CVD prevention. While genetic studies show conflicting results on correlations between HDL-C and CVD, experimental studies have yielded sufficient encouraging data to proceed with the development of HDL-C raising strategies. CETP inhibition has been shown to successfully increase HDL-C levels in man. However, the first CETP inhibitor tested in phase III trials increased mortality possibly due to torcetrapib-specific vasopressor effects. More recently, dalcetrapib did not show an effect on CVD outcome while raising HDL-C by 30%, thereby refuting the HDL-C hypothesis. Anacetrapib and evacetrapib are currently tested in phase III clinical trials and have not shown adverse effects thus far. Both compounds not only increase HDL-C by 129-151%, they also decrease LDL-C (36-41%) and anacetrapib lowers Lp(a) (17%). Combined, these effects are anticipated to decrease CVD risk and the results will be revealed in 2017.
authors: Academic Medical Center, Department of Vascular Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors: A E
authors: AE
authors: Bochem
authors: J A
authors: JA
authors: Kuivenhoven
authors: E S G
authors: ES
authors: Stroes
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D006801:Humans; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D023303:Oxazolidinones; D001569:Benzodiazepines; C568301:evacetrapib; C530884:anacetrapib