title: On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT).
abstract: BACKGROUND
  We aimed to determine the efficacy and safety of adding ezetimibe (Ez) to simvastatin (S) in a post-acute coronary syndrome (ACS) population in a prespecified on-treatment analysis.
  
  
  METHODS
  We evaluated 17,706 post-ACS patients from the IMPROVE-IT trial who had low-density lipoprotein cholesterol values between 50 and 125 mg/dL and who received Ez 10 mg/d with S 40 mg/d (Ez/S) or placebo with simvastatin 40 mg/d (P/S). The primary composite end point was cardiovascular death, myocardial infarction, unstable angina, coronary revascularization ≥30 days postrandomization, or stroke. The on-treatment analysis included patients who received study drug for the duration of the trial or experienced a primary end point or noncardiovascular death within 30 days of drug discontinuation.
  
  
  RESULTS
  Mean low-density lipoprotein cholesterol values at 1 year were 71 mg/dL for P/S and 54 mg/dL for Ez/S (absolute difference -17 mg/dL = -24%; P < .001). The 7-year Kaplan-Meier estimate of the primary end point occurred in 32.4% in the P/S arm and 29.8% in the Ez/S arm (absolute difference 2.6%; HRadj0.92 [95% CI 0.87-0.98]; P = .01). The absolute treatment effect favoring Ez/S was 30% greater than in the intention-to-treat analysis of IMPROVE-IT.
  
  
  CONCLUSIONS
  This analysis provides additional support for the efficacy and safety of adding Ez to S in this high-risk, post-ACS population.
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC. Electronic address: michael.blazing@duke.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Blazing
authors.affiliation: TIMI Study Group, Boston, MA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
authors.affiliation: TIMI Study Group, Boston, MA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: Monash University, Melbourne, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tonkin
authors.affiliation: Baylor College of Medicine and Houston Methodist DeBakey Heart and Vascular Center, Houston, TX.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Lady Davis Carmel Medical Center, Haifa, Israel.
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.affiliation: Merck & Co, Inc., Kenilworth, NJ.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Musliner
authors.affiliation: Merck & Co, Inc., Kenilworth, NJ.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tershakovec
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: White
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Craig
authors.initials: C
authors.lastname: Reist
authors.affiliation: TIMI Study Group, Boston, MA.
authors.forename: Amy
authors.initials: A
authors.lastname: McCagg
authors.affiliation: TIMI Study Group, Boston, MA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects; D008078:Cholesterol, LDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods / Q000706:statistics & numerical data; D000069438:Ezetimibe / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019821:Simvastatin; D000069438:Ezetimibe