Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) trial.

Objectives: The aim of this study was to evaluate the efficacy of polyunsaturated fatty acids (n-3 PUFA) for the prevention of recurrent atrial fibrillation (AF) in patients with normal sinus rhythm.

Background: Current pharmacological treatments to limit recurrent AF in patients with previous AF have limited efficacy and high rates of adverse events. Results of trials that tested the efficacy of n-3 PUFA provided heterogeneous results.

Methods: This was a prospective, randomized, double-blind, placebo-controlled, multicenter trial involving 586 outpatient participants with confirmed symptomatic paroxysmal AF that required cardioversion (n = 428), at least 2 episodes of AF in the 6 months before randomization (n = 55), or both (103). Patients were randomly allocated to n-3 PUFA (1 g/day) or placebo for 12 months. The primary endpoint was symptomatic recurrence of AF.

Results: There were no significant differences between patients allocated to placebo and those who received n-3 PUFA for the main outcome. At 12 months, 56 of 297 participants (18.9%) in the placebo group and 69 of 289 participants (24.0%) in the n-3 PUFA group had a recurrent symptomatic AF (hazard ratio: 1.28, 95% confidence interval: 0.90 to 1.83, p = 0.17). There was no difference between treatment with placebo and n-3 PUFA for any of the other pre-specified endpoints, including the composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding that occurred in 20 (6.7%) and 16 (5.5%) of patients randomized to placebo or n-3 PUFA, respectively (hazard ratio: 0.86, 95% confidence interval: 0.44 to 1.66, p = 0.65).

Conclusions: Pharmacological supplementation with 1 g of n-3 PUFA for 1 year did not reduce recurrent AF. (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation [FORWARD]; NCT00597220).