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.
Keywords: Atherosclerosis, HDL, LDL, cardiovascular risk, lipids, lipoproteins. cholesterol, dyslipidemia.
Current Pharmaceutical Design
Title:The Promise of Cholesteryl Ester Transfer Protein (CETP) Inhibition in the Treatment of Cardiovascular Disease
Volume: 19 Issue: 17
Author(s): A.E. Bochem, J.A. Kuivenhoven and E.S.G. Stroes
Affiliation:
Keywords: Atherosclerosis, HDL, LDL, cardiovascular risk, lipids, lipoproteins. cholesterol, dyslipidemia.
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.
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Cite this article as:
Bochem A.E., Kuivenhoven J.A. and Stroes E.S.G., The Promise of Cholesteryl Ester Transfer Protein (CETP) Inhibition in the Treatment of Cardiovascular Disease, Current Pharmaceutical Design 2013; 19 (17) . https://dx.doi.org/10.2174/1381612811319170022
DOI https://dx.doi.org/10.2174/1381612811319170022 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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