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Recent clinical trials evaluating benefit of drug therapy for modification of HDL cholesterol

Wright, R. Scott

Current Opinion in Cardiology: July 2013 - Volume 28 - Issue 4 - p 389–398
doi: 10.1097/HCO.0b013e328362059d
CLINICAL TRIALS: Edited by Harvey D. White

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.

Division of Cardiology, Mayo Clinic, Minnesota, USA

Correspondence to R. Scott Wright, MD, FACC, FESC, FAHA, Professor of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel: +1 507 284 0783; fax: +1 507 266 0228; e-mail: wright.scott@mayo.edu

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins