title: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.
abstract: BACKGROUND
  Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.
  
  
  METHODS
  We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.
  
  
  RESULTS
  The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups.
  
  
  CONCLUSIONS
  When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).
authors.affiliation: From the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, and Harvard Medical School, Boston (C.P.C., R.P.G., A.M., K.I., E.A.B., S.D.W., E.B.); Duke Clinical Research Institute (DCRI), Durham, NC (M.A.B., J.A.W., C.R., R.M.C.); Montreal Heart Institute, Montreal (P.T.); Vivantes Neukölln Medical Center, Berlin (H.D.); Lady Davis Carmel Medical Center, Haifa, Israel (B.S.L.); Canisius-Wilhelmina Ziekenhuis, Nijmegen (T.O.O.), and the Netherlands Leiden University Medical Center, Leiden (J.W.J.) - both in the Netherlands; Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy (G.M.D.F.); National Institute of Cardiology, Warsaw, Poland (W.R.); and Merck, Kenilworth, NJ (P.D.L., A.M.T., T.A.M.).
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Michael A
authors.initials: MA
authors.lastname: Blazing
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.forename: Amy
authors.initials: A
authors.lastname: McCagg
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: White
authors.forename: Pierre
authors.initials: P
authors.lastname: Theroux
authors.forename: Harald
authors.initials: H
authors.lastname: Darius
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.forename: Ton Oude
authors.initials: TO
authors.lastname: Ophuis
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Gaetano M
authors.initials: GM
authors.lastname: De Ferrari
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.forename: Paul
authors.initials: P
authors.lastname: De Lucca
authors.forename: KyungAh
authors.initials: K
authors.lastname: Im
authors.forename: Erin A
authors.initials: EA
authors.lastname: Bohula
authors.forename: Craig
authors.initials: C
authors.lastname: Reist
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tershakovec
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Musliner
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D019821:Simvastatin; D000069438:Ezetimibe