Anacetrapib is a new drug that raises HDL levels and reduces LDL levels by inhibiting the cholesteryl ester transfer protein (CETP). Another CETP inhibitor, torcetrapib, was withdrawn from development when it was found to increase rates of cardiovascular outcomes and death (JW Cardiol Nov 5 2007). Investigators have now conducted an international, manufacturer-funded, randomized, double-blind, placebo-controlled trial of anacetrapib in 1623 patients (mean age, 63) with or at high risk for coronary disease (55% and 45%, respectively).

By week 24, the mean LDL level had decreased significantly more in anacetrapib patients (from 81 mg/dL to 45 mg/dL) than in placebo patients (from 82 mg/dL to 77 mg/dL). The mean HDL level had increased significantly — and markedly — more with anacetrapib (from 41 mg/dL to 101 mg/dL) than with placebo (from 40 mg/dL to 46 mg/dL). Reductions in apolipoprotein B levels and increases in apolipoprotein A-I levels were greater in anacetrapib patents than in placebo patients — by 21.0% and 44.7%, respectively. All lipid changes persisted throughout the 76-week study period.

Study treatment was discontinued in 143 patients (142 on anacetrapib and 1 on placebo) whose LDL levels fell below 25 mg/dL. The rate of study-drug discontinuation for other reasons was similar in the two groups (14.6% and 17.4%, respectively). The rate of adverse events did not differ appreciably between the two groups. A prespecified, adjudicated safety endpoint (cardiovascular death, myocardial infarction, hospitalization for unstable angina, or stroke) occurred in 2.0% of anacetrapib patients and 2.6% of placebo patients, a nonsignificant difference. In all, 11 patients in the anacetrapib group and 8 in the placebo group died.

Comment: It is important to note that this study was designed to assess safety and changes in lipid levels, and that it was underpowered to assess the efficacy of anacetrapib for preventing clinical cardiovascular events. Nonetheless, anacetrapib demonstrated profound LDL-lowering and HDL-raising effects and appeared to have none of the adverse cardiovascular effects observed with torcetrapib. These results provide a strong rationale for the large clinical outcomes trial that will surely follow.

— Joel M. Gore, MD

Published in Journal Watch Cardiology November 17, 2010

Citation(s):

Cannon CP et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med 2010 Nov 16; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa1009744).

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Review and add to remarks on this article

• prognosis
  JJ Mendoza, issste hospital, 18 Nov 2010 1:20 PM EST
  Specialty: Cardiovascular Disease
  do exist any large observational placebo control study with this drug related to improve cardiovascular morbimortality?