title: Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population.
abstract: BACKGROUND
  The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is evaluating the potential benefit for reduction in major cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40 mg/d of simvastatin therapy in patients who present with acute coronary syndromes and have low-density lipoprotein cholesterol (LDL-C) ≤ 125 mg/dL.
  
  
  METHODS
  The primary composite end point is CV death, nonfatal myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina (UA), and coronary revascularization (≥ 30 days postrandomization). The simvastatin monotherapy arm's LDL-C target is <70 mg/dL. Ezetimibe was assumed to further lower LDL-C by 15 mg/dL and produce an estimated ~8% to 9% treatment effect. The targeted number of events is 5,250.
  
  
  RESULTS
  We enrolled 18,144 patients with either ST-segment elevation MI (STEMI, n = 5,192) or UA/non-ST-segment elevation MI (UA/NSTEMI, n = 12,952) from October 2005 to July 2010. Western Europe (40%) and North America (38%) were the leading enrolling regions. The STEMI cohort was younger and had a higher percentage of patients naive to lipid-lowering treatment compared with the UA/NSTEMI cohort. The UA/NSTEMI group had a higher prevalence of diabetes, hypertension, and prior MI. Median LDL-C at entry was 100 mg/dL for STEMI and 93 mg/dL for UA/NSTEMI patients.
  
  
  CONCLUSIONS
  This trial is evaluating LDL-C lowering beyond previously targeted LDL-C levels. The results depend on achieving the desired separation of LDL-C with ezetimibe and on the assumption that ezetimibe's lowering of LDL-C will have similar event reduction efficacy as the LDL-C lowering from a statin. The results could affect future therapies and guidelines.
authors: Duke Clinical Research Institute, Durham, NC. Electronic address: michael.blazing@dm.duke.edu.
authors: Michael A
authors: MA
authors: Blazing
authors: Thrombolysis in Myocardial Infarction [TIMI] Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
authors: Robert P
authors: RP
authors: Giugliano
authors: Thrombolysis in Myocardial Infarction [TIMI] Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
authors: Christopher P
authors: CP
authors: Cannon
authors: Merck & Co., Rahway, NJ.
authors: Thomas A
authors: TA
authors: Musliner
authors: Merck & Co., Rahway, NJ.
authors: Andrew M
authors: AM
authors: Tershakovec
authors: Duke Clinical Research Institute, Durham, NC.
authors: Jennifer A
authors: JA
authors: White
authors: Duke Clinical Research Institute, Durham, NC.
authors: Craig
authors: C
authors: Reist
authors: Thrombolysis in Myocardial Infarction [TIMI] Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
authors: Amy
authors: A
authors: McCagg
authors: Thrombolysis in Myocardial Infarction [TIMI] Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
authors: Eugene
authors: E
authors: Braunwald
authors: Duke Clinical Research Institute, Durham, NC.
authors: Robert M
authors: RM
authors: Califf
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects*; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000069438:Ezetimibe