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.