The promise of cholesteryl ester transfer protein (CETP) inhibition in the treatment of cardiovascular disease

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 t...

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Bibliographic Details
Published inCurrent pharmaceutical design Vol. 19; no. 17; p. 3143
Main Authors Bochem, A E, Kuivenhoven, J A, Stroes, E S G
Format Journal Article
LanguageEnglish
Published United Arab Emirates 2013
Subjects
Animals
Benzodiazepines - pharmacology
Benzodiazepines - therapeutic use
Cardiovascular Diseases - drug therapy
Cholesterol Ester Transfer Proteins - antagonists & inhibitors
Cholesterol Ester Transfer Proteins - genetics
Cholesterol, HDL - blood
Humans
Oxazolidinones - pharmacology
Oxazolidinones - therapeutic use
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Summary: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.
ISSN:1873-4286
DOI:10.2174/1381612811319170022