Safety of inhibition of cholesteryl ester transfer protein with anacetrapib: the DEFINE study

Abstract

Inhibition of cholesteryl ester transfer protein is a strategy under investigation for raising HDL cholesterol levels and addressing residual cardiovascular risk after effective reduction of LDL cholesterol. In the Phase III DEFINE trial conducted in patients with or at high risk for coronary heart disease, anacetrapib reduced LDL cholesterol levels by 39.8% after 24 weeks compared with placebo and demonstrated an acceptable safety profile through 76 weeks of treatment (the primary end points). Anacetrapib caused a placebo-adjusted 138.1% increase in HDL cholesterol levels, with no alterations in blood pressure, aldosterone or electrolytes. The trial also provided reassurance that anacetrapib would not be associated with a 25% increase in cardiovascular events, as seen with a previous cholesteryl ester transfer protein inhibitor. Sustained effects on lipids were observed 12 weeks following cessation of anacetrapib treatment. Anacetrapib is being evaluated in an ongoing cardiovascular outcomes trial.

Keywords::

• anacetrapib
• cholesteryl ester transfer protein inhibitor
• clinical trial
• coronary heart disease
• HDL cholesterol
• lipid-modifying therapy

Financial & competing interests disclosure

AM Gotto Jr is a consultant for AstraZeneca, Janssen, Kowa, Merck and Roche and serves on the Board of Directors for Aegerion Pharmaceuticals and Arisaph Pharmaceuticals. He is a member of advisory boards for DuPont, Haptocure, VascuVis and Vatera Capital. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.