title: Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.
abstract: BACKGROUND
  Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid-lowering studies have had conflicting results.
  
  
  METHODS
  We conducted a randomized, double-blind trial involving 1873 patients with mild-to-moderate, asymptomatic aortic stenosis. The patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily. The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes, aortic-valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary-artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events.
  
  
  RESULTS
  During a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35.3%) in the simvastatin-ezetimibe group and in 355 patients (38.2%) in the placebo group (hazard ratio in the simvastatin-ezetimibe group, 0.96; 95% confidence interval [CI], 0.83 to 1.12; P=0.59). Aortic-valve replacement was performed in 267 patients (28.3%) in the simvastatin-ezetimibe group and in 278 patients (29.9%) in the placebo group (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P=0.97). Fewer patients had ischemic cardiovascular events in the simvastatin-ezetimibe group (148 patients) than in the placebo group (187 patients) (hazard ratio, 0.78; 95% CI, 0.63 to 0.97; P=0.02), mainly because of the smaller number of patients who underwent coronary-artery bypass grafting. Cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P=0.01).
  
  
  CONCLUSIONS
  Simvastatin and ezetimibe did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis. Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis. (ClinicalTrials.gov number, NCT00092677.)
authors.affiliation: Division of Cardiology, Aker University Hospital, Trondheimsveien 235, N-0514 Oslo, Norway. anne@rossebo.net
authors.forename: Anne B
authors.initials: AB
authors.lastname: Rossebø
authors.forename: Terje R
authors.initials: TR
authors.lastname: Pedersen
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.forename: Philippe
authors.initials: P
authors.lastname: Brudi
authors.forename: John B
authors.initials: JB
authors.lastname: Chambers
authors.forename: Kenneth
authors.initials: K
authors.lastname: Egstrup
authors.forename: Eva
authors.initials: E
authors.lastname: Gerdts
authors.forename: Christa
authors.initials: C
authors.lastname: Gohlke-Bärwolf
authors.forename: Ingar
authors.initials: I
authors.lastname: Holme
authors.forename: Y Antero
authors.initials: YA
authors.lastname: Kesäniemi
authors.forename: William
authors.initials: W
authors.lastname: Malbecq
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Nienaber
authors.forename: Simon
authors.initials: S
authors.lastname: Ray
authors.forename: Terje
authors.initials: T
authors.lastname: Skjaerpe
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
authors.forename: Ronnie
authors.initials: R
authors.lastname: Willenheimer