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

Eliot A. Brinton, Uma Kher, Sukrut Shah, Christopher P. Cannon, Michael Davidson, Antonio M. Gotto, Tanya B. Ashraf, Christine Mc Crary Sisk, Hayes Dansky, Yale Mitchel, Philip Barter, Investigators DEFINE Investigators

Research output: Contribution to journalArticle

22 Scopus citations

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 Lipidmodification (REVEAL).

Original languageEnglish (US)
Pages (from-to)65-71
Number of pages7
JournalJournal of Clinical Lipidology
Volume9
Issue number1
DOIs
StatePublished - 2015

Keywords

  • Anacetrapib
  • Cholesteryl ester transfer
  • High-density lipoproteins
  • Low-density lipoproteins
  • Plasma triglycerides
  • Protein inhibitors

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

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