title: The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial.
abstract: To examine the efficacy and safety of ezetimibe added to statin in patients with prior coronary artery bypass graft surgery (CABG) following hospitalization for an acute coronary syndrome (ACS).
  
  
  
  In the IMPROVE-IT trial, post-ACS patients with mean low density lipoprotein cholesterol (LDL-C) of 93.8 mg/dL at presentation were randomized to simvastatin/ezetimibe or simvastatin/placebo. The primary endpoint was cardiovascular death, major coronary event or stroke, and the median follow-up was 6 years. Efficacy and safety endpoints were examined by prior CABG status. Among 18 134 patients, 1684 (9.3%) had a prior CABG (median age 69 years, 82% male). During the trial, the median time-weighted LDL-C level was 55.0 mg/dL with simvastatin/ezetimibe vs. 69.9 mg/dL with simvastatin/placebo in patients with prior CABG (P < 0.001), and it was 53.6 mg/dL vs. 69.5 mg/dL, respectively, in patients without prior CABG (P < 0.001). The rate of the primary endpoint was higher in patients with vs. without prior CABG [56% vs. 32%, adj. hazard ratio 1.45, 95% confidence interval (CI) 1.33-1.58]. Patients with prior CABG receiving simvastatin/ezetimibe had an 8.8% (95% CI 3.1-14.6%) lower absolute risk over simvastatin/placebo in the primary endpoint, whereas patients without prior CABG had a 1.3% (95% CI 0-2.6%) lower absolute risk (P-interaction = 0.02). There were no between-group significant differences in safety endpoints.
  
  
  
  The clinical benefit of adding ezetimibe to statin appears to be enhanced in patients with prior CABG, supporting the use of intensive lipid lowering therapy in these high-risk patients following ACS.
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA.
authors: Alon
authors: A
authors: Eisen
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA.
authors: Christopher P
authors: CP
authors: Cannon
authors: Duke Clinical Research Institute, Durham, NC, USA.
authors: Michael A
authors: MA
authors: Blazing
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA.
authors: Erin A
authors: EA
authors: Bohula
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA.
authors: Jeong-Gun
authors: JG
authors: Park
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA.
authors: Sabina A
authors: SA
authors: Murphy
authors: Duke Clinical Research Institute, Durham, NC, USA.
authors: Jennifer A
authors: JA
authors: White
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA.
authors: Robert P
authors: RP
authors: Giugliano
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA ebraunwald@partners.org.
authors: Eugene
authors: E
authors: Braunwald
mesh_terms: D054058:Acute Coronary Syndrome; D000368:Aged; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008297:Male; D019821:Simvastatin; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000069438:Ezetimibe
keywords:  coronary artery bypass graft; acute coronary syndrome; cardiovascular events; ezetimibe; statin