title: Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study.
abstract: BACKGROUND
  Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS).
  
  
  METHODS
  Asymptomatic patients with mild-to-moderate AS (n = 1,421) were randomized (1:1) to double-blind simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years. The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram at a core laboratory reading center. Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events.
  
  
  RESULTS
  During the course of the study, new-onset AF was detected in 85 (6%) patients (14.2/1,000 person-years of follow-up). At baseline, patients who developed AF were, compared with those remaining in sinus rhythm, older and had a higher left ventricular mass index a smaller aortic valve area index. Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717). In contrast, age (hazard ratio [HR] 1.07 [95% CI 1.05-1.10], P < .001) and left ventricular mass index (HR 1.01 [95% CI 1.01-1.02], P < .001) were independent predictors of new-onset AF. The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes (HR 1.65 [95% CI 1.02-2.66], P = .04) and 4-fold higher risk of nonfatal nonhemorrhagic stroke (HR 4.04 [95% CI 1.18-13.82], P = .03).
  
  
  CONCLUSIONS
  Simvastatin and ezetimibe were not associated with less new-onset AF. Older age and greater left ventricular mass index were independent predictors of AF development. New-onset AF was associated with a worsening of prognosis.
authors.affiliation: Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark. casperbang@hotmail.com
authors.forename: Casper N
authors.initials: CN
authors.lastname: Bang
authors.forename: Anders M
authors.initials: AM
authors.lastname: Greve
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.forename: Kenneth
authors.initials: K
authors.lastname: Egstrup
authors.forename: Christa
authors.initials: C
authors.lastname: Gohlke-Baerwolf
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Nienaber
authors.forename: Simon
authors.initials: S
authors.lastname: Ray
authors.forename: Anne B
authors.initials: AB
authors.lastname: Rossebø
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001024:Aortic Valve Stenosis / Q000150:complications*; D001281:Atrial Fibrillation / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D001384:Azetidines / Q000627:therapeutic use*; D004311:Double-Blind Method; D000069438:Ezetimibe; D005260:Female; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D019821:Simvastatin / Q000627:therapeutic use*; D020521:Stroke / Q000453:epidemiology; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D019821:Simvastatin; D000069438:Ezetimibe