A review questions whether CETP inhibition can reduce cardiovascular events given the complex link between CETP loss-of-function and coronary risk (Curr Cardiol Rep 2011)

Based on epidemiologic studies conducted throughout the world, it is established that there is an inverse relationship between high-density lipoprotein cholesterol (HDL-C) and risk for coronary artery disease (CAD). The incidence of low HDL-C is high and increasing throughout the world. A variety of pharmacologic approaches are being developed to therapeutically modulate serum levels of HDL-C. One controversial approach to this is the use of molecules that inhibit the activity of cholesteryl ester transfer protein (CETP), an enzyme involved in neutral lipid transfer between lipoproteins. The inhibition of CETP can lead to substantial elevations in HDL-C. Based on a number of considerations, including the complex relationship between loss of function mutations in CETP and risk for CAD and the clinical experience with torcetrapib, it is difficult to predict if CETP inhibition will be associated with reductions in rates of atherosclerosis disease progression and risk for cardiovascular events.