Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib.

Full Abstract

BACKGROUND: Residual cardiovascular (CV) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol (LDL-C). New therapies to raise high-density lipoprotein cholesterol (HDL-C) are currently being investigated. Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that raises HDL-C and reduces LDL-C when administered alone or with a statin. Adverse effects on blood pressure, electrolytes, and aldosterone levels, seen with another drug in this class, have not been noted in studies of anacetrapib to date. METHODS: Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHD risk equivalents (clinical trials.gov NCT00685776). Eligible patients at National Cholesterol Education Program-Adult Treatment Panel III LDL-C treatment goal on a statin, with or without other lipid-modifying medications, are treated with anacetrapib, 100 mg, or placebo for 18 months, followed by a 3-month, poststudy follow-up. The primary end points are percent change from baseline in LDL-C and the safety and tolerability of anacetrapib. Comprehensive preplanned interim safety analyses will be performed at the 6- and 12-month time points to examine treatment effects on key safety end points, including blood pressure and electrolytes. A preplanned Bayesian analysis will be performed to interpret the CV event distribution, given the limited number of events expected in this study. RESULTS: A total of 2,757 patients were screened at 153 centers in 20 countries, and 1,623 patients were randomized into the trial. Lipid results, clinical CV events, and safety outcomes from this trial are anticipated in 2010.

Author information

Author/s: Cannon, Christopher P (CP); Dansky, Hayes M (HM); Davidson, Michael (M); Gotto, Antonio M (AM); Brinton, Eliot A (EA); Gould, A Lawrence (AL); Stepanavage, Michael (M); Liu, Sherry Xueyu (SX); Shah, Sukrut (S); Rubino, Joseph (J); Gibbons, Patrice (P); Hermanowski-Vosatka, Anne (A); Binkowitz, Bruce (B); Mitchel, Yale (Y); Barter, Philip (P); DEFINE investigators;

Affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA. cpcannon(-atsign-)partners.org

Journal and publication information

Publication Type: Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Journal: American heart journal (Am Heart J), published in United States. (Language: eng)

Reference: 2009-Oct; vol 158 (issue 4) : pp 513-519.e3

Dates: Created 2009/09/28; Completed 2009/10/20;

PMID: 19781408, status: MEDLINE (last retrieval date: 10/20/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.