Effects of anacetrapib on plasma lipids in specific patient subgroups in the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) trial.

Abstract

BACKGROUND:

In the Determining the Efficacy and Tolerability of cholesteryl ester transfer protein (CETP) INhibition with AnacEtrapib (DEFINE) trial, anacetrapib added to statin produced robust low-density lipoprotein cholesterol (LDL-C)-lowering and high-density lipoprotein cholesterol (HDL-C)-raising vs placebo in patients with coronary heart disease (CHD). Predictors of the degree of LDL-C and HDL-C responses to anacetrapib, however, are poorly understood.

OBJECTIVE:

Lipid effects of anacetrapib in patient subgroups within the DEFINE trial (clinicaltrials.gov: NCT00685776) are reported.

METHODS:

The percent of placebo-corrected changes from baseline for LDL-C (estimated by Friedewald calculation [Fc-LDL-C]) and HDL-C after 24 weeks of anacetrapib 100 mg/day were compared among patients by age, gender, race, diabetes status, type of concomitant statin with or without other lipid therapies, and baseline HDL-C, Fc-LDL-C, and triglyceride (TG) levels.

RESULTS:

Percent decreases in Fc-LDL-C and increases in HDL-C with anacetrapib were similar (magnitude of difference generally <1/5 of the overall treatment effect) across subgroups by age, gender, diabetes status, lipid-modifying regimen, and baseline Fc-LDL-C, HDL-C, or TG. On the other hand, anacetrapib effects on Fc-LDL-C (-24% vs -41%) and HDL-C (+75% vs +139%) appeared to be less in black vs white patients, respectively.

CONCLUSION:

Effects of anacetrapib on Fc-LDL-C and HDL-C were generally comparable across subgroups, including being relatively independent of baseline Fc-LDL-C, HDL-C, or TG levels. The clinical impact of the lipid-modifying effects of anacetrapib is being evaluated in the cardiovascular disease outcomes trial, Randomized EValuation of the Effects of Anacetrapib though Lipid-modification (REVEAL).

• Authors: Eliot A Brinton, Uma Kher, Sukrut Shah, Christopher P Cannon, Michael Davidson, Antonio M Gotto, Tanya B Ashraf, Christine McCrary Sisk, Hayes Dansky, Yale Mitchel, Philip Barter, DEFINE Investigators
• Journal: Journal of clinical lipidology (J Clin Lipidol) 2015 Jan-Feb Vol. 9 Issue 1 Pg. 65-71 ISSN: 1933-2874 [Print] United States
• PMID: 25670362 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anticholesteremic Agents
• CETP protein, human
• Cholesterol Ester Transfer Proteins
• Cholesterol, HDL
• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipids
• Oxazolidinones
• anacetrapib

Topics

• Aged
• Anticholesteremic Agents (therapeutic use)
• Cholesterol Ester Transfer Proteins (antagonists & inhibitors, metabolism)
• Cholesterol, HDL (blood)
• Cholesterol, LDL (blood)
• Coronary Disease (drug therapy)
• Double-Blind Method
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Least-Squares Analysis
• Lipids (blood)
• Male
• Middle Aged
• Oxazolidinones (therapeutic use)
• Placebo Effect
• Treatment Outcome