title: 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.
  
  
  CONCLUSIONS
  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: Department of Atherometabolic Research, Utah Foundation for Biomedical Research, Utah Lipid Center, Salt Lake City, UT, USA. Electronic address: eliot.brinton@utah.edu.
authors: Eliot A
authors: EA
authors: Brinton
authors: Biostatistics, Merck & Co., Inc., Kenilworth, NJ, USA.
authors: Uma
authors: U
authors: Kher
authors: Clinical Research, Merck & Co., Inc., Kenilworth, NJ, USA.
authors: Sukrut
authors: S
authors: Shah
authors: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
authors: Christopher P
authors: CP
authors: Cannon
authors: Radiant Research, Chicago, IL, USA.
authors: Michael
authors: M
authors: Davidson
authors: Cardiac Disease Prevention, Weill Cornell Medical College, New York, NY, USA.
authors: Antonio M
authors: AM
authors: Gotto
authors: Clinical Operations, Merck & Co., Inc., Kenilworth, NJ, USA.
authors: Tanya B
authors: TB
authors: Ashraf
authors: Scientific Affairs, Merck & Co., Inc., Kenilworth, NJ, USA.
authors: Christine
authors: C
authors: McCrary Sisk
authors: Early Discovery, Merck & Co., Inc., Kenilworth, NJ, USA.
authors: Hayes
authors: H
authors: Dansky
authors: Clinical Research, Merck & Co., Inc., Kenilworth, NJ, USA.
authors: Yale
authors: Y
authors: Mitchel
authors: Centre for Vascular Research, University of New South Wales, Sydney, Australia.
authors: Philip
authors: P
authors: Barter
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D016018:Least-Squares Analysis; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000627:therapeutic use*; D015990:Placebo Effect; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D023303:Oxazolidinones; C530884:anacetrapib
keywords: Anacetrapib; Cholesteryl ester transfer protein inhibitors; High-density lipoproteins; Low-density lipoproteins; Plasma triglycerides