A.E. Bochem, J.A. Kuivenhoven and E.S.G. Stroes Pages 3143 - 3149 ( 7 )
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.
Atherosclerosis, HDL, LDL, cardiovascular risk, lipids, lipoproteins. cholesterol, dyslipidemia.
Academic Medical Center, Department of Vascular Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.