Review narrates the CETP inhibitor class from the mortality excess of torcetrapib to the still-pending REVEAL and ACCELERATE trials (Curr Opin Cardiol 2013)

Purpose Of Review: To highlight the recent data evaluating pharmacological manipulation of HDL cholesterol (HDL-C) and examine whether medication-induced changes were associated with improved clinical outcomes and reduced short-term and long-term cardiovascular risks. The review focuses on the studies with niacin and the new cholesteryl ester transfer protein (CETP) inhibitors torcetrapib, dalcetrapib, anacetrapib and evacetrapib.

Recent Findings: Several large randomized clinical trials have evaluated drug therapy on HDL-C and cardiovascular outcomes. Two studies have evaluated the clinical outcomes following HDL-C raising with niacin. Data from the Heart Protection 2 Treatment of HDL to Reduce the Incidence of Vascular Events and The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health trials both demonstrated no clinical benefit from use of niacin therapy when added to background statin therapy with regard to short-term and long-term cardiovascular risk reduction. Both studies demonstrated excess side-effects from use of niacin. A number of clinical trials have evaluated HDL-C modification from use of a CETP inhibitor. All of the studies have demonstrated significant increases in HDL-C. To date, the outcome data are not favorable. Use of torcetrapib was associated with excess mortality. Use of dalcetrapib had no effect on short-term and long-term cardiovascular events. Two outcome studies with anacetrapib and evacetrapib are ongoing and will report out in a few years' time.

Summary: Pharmacological manipulation of HDL-C has not improved the cardiovascular outcomes. Several agents have caused harm or unacceptable side-effects. Further studies are needed before one can recommend the use of additional lipid-modifying therapies beyond statins.