The potential for CETP inhibition to reduce cardiovascular disease risk

ABSTRACT

Background: Although reductions in cardiovascular risk can be achieved by lowering low-density lipoprotein cholesterol, treated patients remain at substantial risk. Epidemiological studies have established that higher levels of high-density lipoprotein cholesterol (HDL-C) are strongly associated with reduced cardiovascular risk, and therefore raising levels of HDL-C may be beneficial. The activity of cholesteryl ester transfer protein (CETP) appears to be inversely correlated with HDL-C levels and thus CETP is an attractive target for intervention to raise levels of HDL-C and potentially reduce residual cardiovascular risk.

Objectives: This paper reviews the evidence for an atheroprotective role of higher levels of HDL‐C, the function of CETP in cholesterol metabolism, and the concept of CETP inhibition as a potential new strategy for decreasing cardiovascular risk. An analysis of clinical studies of CETP inhibition was also performed.

Methods: MEDLINE (1966 to June 2006), EMBASE (1974 to June 2006), and cardiology conference proceedings were searched for clinical trials of CETP inhibition.

Results: Thirteen reports involving vaccine-based and pharmacological inhibition of CETP were found. Modest and inconsistent elevation of HDL‐C was observed with vaccine-based therapy, whereas HDL-C elevation with pharmacological inhibitors was greater and more consistent.

Conclusions: Elevation of HDL‐C via CETP inhibition appears to be a potentially promising approach to reduce cardiovascular disease. Preliminary studies suggest benefits of CETP inhibition on serum lipid levels, and ongoing studies should establish the effects on atherosclerosis and cardiovascular events.

Key words: :

• CETi‐1
• Investigational drugs
• JTT‐705
• Torcetrapib