November 17, 2010
2 min read

DEFINE: Anacetrapib raises HDL, lowers LDL

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

American Heart Association Scientific Sessions 2010

CHICAGO — The experimental cholesteryl ester transfer protein inhibitor anacetrapib was associated with marked increases in HDL levels and decreases in LDL levels without raising BP, according to new study results.

Researchers for the Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib (DEFINE) trial enrolled 1,623 patients with or at high risk for CHD taking statins and randomly assigned in a double-blinded, 1:1 fashion to receive either 100 mg daily of anacetrapib (n=811; Merck) or placebo (n=812). The primary outcomes of interest were the percent changes from baseline in LDL at 24 weeks, with percent changes from baseline in HDL as a secondary endpoint.

According to the study results, LDL was reduced by 39.8% from 81 mg/dL to 45 mg/dL (P<.001) in patients taking anacetrapib vs. placebo. The researchers also reported a 138.1% increase in HDL levels in the anacetrapib group (from 41 mg/dL at baseline to 101 mg/dL at 24 weeks; P<.001). There were no reported changes in BP through 76 weeks, nor were changes in electrolyte or aldosterone levels reported.

Additionally, prespecified adjudicated CV events occurred in 16 patients in the anacetrapib group vs. 21 in the placebo group (P=.40). Torcetrapib, a previously evaluated cholesteryl ester transfer protein inhibitor, was associated with an increase in CV events, but the researchers suggested that the event distribution in DEFINE (via Bayesian analysis) yielded a predictive probability of 94% that anacetrapib would not be associated with a 25% increase in CV events seen with torcetrapib.

“We’re very encouraged with these results,” Christopher P. Cannon, MD, of Brigham and Women’s Hospital in Boston and senior investigator of the TIMI study group, said in a press conference. “This is a moderate-sized safety study, so we have reassurance that we can move forward and really test this [drug].”

Cannon and Rory Collins, MD, FAHA, professor at Oxford University, announced the next step in testing anacetrapib – a study enrolling 30,000 patients with heart disease and a background of statin use. The study is scheduled to have 4-year follow-up.

The DEFINE study was funded by Merck Research Laboratories. – by Eric Raible and Stacey Fisher

For more information:

  • Cannon C. LBCT IV, Abstract 21824. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.


The results [of this study] mean that it’s (anacetrapib) very potent with an impressive change in the lipid profile. Such change is incurred without increases in BP, and lipid changes are likely to provide prognostic benefit. However, it remains to be shown that the HDL particle during treatment with anacetrapib is actually becoming biologically normal. And what is further required, well, we heard it already – proof of outcome benefit in a large, randomized trial, and we heard that this is on the way.

– Thomas Luscher, MD
Professor and Chairman of Cardiology
University Hospital Zurich, Switzerland

Twitter Follow on Twitter.