Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study

Am Heart J. 2012 Apr;163(4):690-6. doi: 10.1016/j.ahj.2012.01.026.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticholesteremic Agents / therapeutic use*
  • Aortic Valve Stenosis / complications*
  • Atrial Fibrillation / diagnostic imaging
  • Atrial Fibrillation / epidemiology
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / pathology
  • Atrial Fibrillation / prevention & control*
  • Azetidines / therapeutic use*
  • Double-Blind Method
  • Ezetimibe
  • Female
  • Heart Ventricles / pathology
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Simvastatin / therapeutic use*
  • Stroke / epidemiology
  • Time Factors
  • Ultrasonography

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Simvastatin
  • Ezetimibe