Statin therapy for the prevention of atrial fibrillation trial (SToP AF trial)

J Cardiovasc Electrophysiol. 2011 Apr;22(4):414-9. doi: 10.1111/j.1540-8167.2010.01925.x. Epub 2010 Oct 13.

Abstract

Background: Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation (NCT00252967).

Methods and results: In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n = 33) or placebo (n = 31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers (high-sensitivity C- reactive protein [hs-CRP], interleukin-6 [IL-6], interleukin-1β[IL-1β], tumor necrosis factor alpha [TNFα]) were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (P = 0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, P = 0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median [IR]: 29 [2-145] days versus 22 [7-70] days, P = 0.9). Although no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, P = 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, P = 0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (P = 0.03).

Conclusions: High-dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Atorvastatin
  • Atrial Fibrillation / blood*
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / prevention & control*
  • Biomarkers / blood
  • Double-Blind Method
  • Electric Countershock / adverse effects
  • Electric Countershock / methods
  • Female
  • Follow-Up Studies
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Oxidative Stress / physiology
  • Pyrroles / therapeutic use*
  • Treatment Outcome

Substances

  • Biomarkers
  • Heptanoic Acids
  • Inflammation Mediators
  • Pyrroles
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT00252967