Good Results For Anacetrapib Trial For Those With Coronary Heart Disease

Editor's Choice
Main Category: Heart Disease
Also Included In: Cardiovascular / Cardiology;  Cholesterol
Article Date: 17 Nov 2010 - 19:00 PST


A Phase III trial showed that Merck's investigational CETP inhibitor, Anacetrapib lowered bad cholesterol (LDL) and raised good cholesterol (HDL) considerably in patients with coronary heart disease or risk equivalents, researchers have reported in the NEJM (New England Journal of Medicine). Of note, is that Anacetrapib's impact on blood cholesterol levels are achieved without the safety concerns that were present with its predecessor, torcetrapib.

The trial, known as DEFINE (Determining the EFficacy and Tolerability of CETP Inhibition with AnacEtrapib), involving 1,623 showed no significant differences from a placebo in the primary safety measures of the study. There were no significant differences in blood pressure, serum electrolytes, or aldeosterone levels.

By week 76 of the trial, 16 anacetrapib patients (2%) had myocardial infarction, stroke, unstable angina or cardiovascular death, compared to 21 (2.6%) on the placebo.

At week 24 LDL cholesterol dropped by 40% and HDL cholesterol rose by 138% in the anacetrapib group.

Michael Mendelsohn, M.D., senior VP and franchise head, Cardiovascular, Merck Research Laboratories, said:

"These results are promising and serve as the basis for our decision to further develop anacetrapib. We look forward to continuing to study anacetrapib in a large cardiovascular clinical outcomes trial."

DEFINE, a randomized, double-blind, placebo-controlled trial, lasted 18-months and included 1,600 participants in 20 different countries at high risk of coronary heart disease. They were all already on statins and were at guideline-established LDL cholesterol goal. The study's aim was to determine how good the drug was at modifying lipid levels, as well as checking its safety and tolerability in doses of 100mg daily, added to ongoing statin treatment, with or without other lipid-modifying agents.

The authors concluded in their NEJM report:

Treatment with anacetrapib had robust effects on LDL and HDL cholesterol, had an acceptable side-effect profile, and, within the limits of the power of this study, did not result in the adverse cardiovascular effects observed with torcetrapib.

"Safety of Anacetrapib in Patients with or at High Risk for Coronary Heart Disease"
Christopher P. Cannon, M.D., Sukrut Shah, Ph.D., R.Ph., Hayes M. Dansky, M.D., Michael Davidson, M.D., Eliot A. Brinton, M.D., Antonio M. Gotto, Jr., M.D., D.Phil., Michael Stepanavage, M.S., Sherry Xueyu Liu, M.S., Patrice Gibbons, M.S., Tanya B. Ashraf, B.A., Jennifer Zafarino, M.S., Yale Mitchel, M.D., and Philip Barter, M.D., Ph.D. for the DEFINE Investigators
NEJM November 17, 2010 (10.1056/NEJMoa1009744)


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