A review finds genetic and plasma CETP-level studies give no clear answer on whether CETP inhibition will reduce atherosclerosis risk (Curr Drug Targets Cardiovasc Haematol Disord 2005)

Original title: Increasing high-density lipoprotein cholesterol through cholesteryl Ester transfer protein inhibition: a next step in the fight against cardiovascular disease?

Curr Drug Targets Cardiovasc Haematol Disord · 1 December 2005 · 5

Van der Steeg WA, El-Harchaoui K, Kuivenhoven JA, Kastelein JJ

This review examines cholesteryl ester transfer protein (CETP), its role in human lipid metabolism, and its relationship to atherosclerotic disease, as a candidate next step in cardiovascular prevention beyond LDL cholesterol lowering. Two small-molecule compounds, JTT-705 and torcetrapib, had been shown to effectively raise HDL cholesterol in humans without significant side effects, alone or combined with statins. However, the review notes that data from studies of genetic CETP deficiency, as well as studies relating plasma CETP levels to atherosclerosis risk, do not provide clear answers on whether raising HDL through CETP inhibition will translate into reduced atherosclerotic disease risk. Several long-term clinical studies addressing this question had recently been initiated, with results expected within the following years.

Original abstract

Over the past decades, lowering of LDL-cholesterol (LDL-c) levels has been established as the foundation for preventing atherosclerotic disease. It is, however, widely accepted that additional risk reduction has to come from modifying other risk factors than LDL-c. In this context, increasing HDL-cholesterol (HDL-c) levels by pharmacological inhibition of the cholesteryl ester transfer protein (CETP) is currently under intense investigation. Two small-molecule compounds, JTT-705 and Torcetrapib, have been shown to effectively increase HDL-c levels in humans, without inducing clinically significant side effects when used as monotherapy or combined with statins. Whether this approach will translate into a reduction in risk of atherosclerotic disease has not yet been established. Data from studies focusing on genetic CETP deficiency as well as those studying the relationship between CETP plasma levels and risk of atherosclerosis do not provide clear answers. Several long-term clinical studies addressing this crucial issue have recently been initiated, results of which will follow within the next few years. This review focuses on CETP, its role in human lipid metabolism and its relation to atherosclerotic disease. Furthermore, it summarizes the currently available data regarding pharmacological CETP inhibition. Finally, it will highlight a number of issues basic to the considerations of whether CETP inhibition will fulfill its promises.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.