Fish Oil Research With Omega-3 for Atrial Fibrillation Recurrence Delaying - FORWARD


Data on the role of omega-3 supplementation in maintaining normal sinus rhythm (NSR) in patients with atrial fibrillation (AF) (secondary prevention) have been mixed. The current trial sought to compare the efficacy of 1 g daily of n-3 polyunsaturated fatty acid (PUFA) for the maintenance of NSR in patients with AF.


Omega-3 supplementation with 1 g daily of n-3 PUFA would be efficacious in maintaining NSR in patients with AF.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Age ≥21 years
  • Outpatient diagnosis of previous symptomatic AF (paroxysmal or persistent) AF who were currently in NSR
  • ≥2 symptomatic episodes of documented AF in the 6 months before randomization, with the last episode occurring within 3-90 days before randomization (paroxysmal AF), or successful electrical or pharmacological cardioversion for persistent AF performed within 3-28 days before randomization
  • If age <65 years, must have ≥1 characteristic of moderate to high risk of stroke

    Number of screened applicants: 1,967
    Number of enrollees: 586
    Duration of follow-up: 1 year
    Mean patient age: 66.1 years
    Percentage female: 45%
    Ejection fraction: 60%


  • Lone AF
  • CHF (class IV)
  • Acute coronary syndrome or cardiac surgery in the previous 3 months
  • Significant valvular disease
  • Wolff-Parkinson-White syndrome
  • Planned or recent implantation of cardiac devices
  • Ablative treatment for AF
  • Any arrhythmia associated with an acute reversible condition, chronic obstructive pulmonary disease, pregnancy or lactation

Primary Endpoints:

  • Time to first recurrence of symptomatic or asymptomatic AF documented by a 12-lead ECG

Secondary Endpoints:

  • Hierarchical composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, CHF development, severe bleeding
  • All-cause hospitalizations
  • Survival free of thromboembolic events
  • Hospitalizations for cardiovascular reasons

Drug/Procedures Used:

Patients with symptomatic paroxysmal or persistent AF were randomized in a 1:1 fashion to either 1 g daily of n-3 PUFA (which provide 850-882 mg eicosapentaenoic acid/docosahexaenoic acid ethyl esters) or matching placebo (olive oil).

Concomitant Medications:

Amiodarone (64%), beta-blockers (61%), aspirin (51%), anticoagulation (42%)

Principal Findings:

A total of 586 patients were randomized, 289 to n-3 PUFA and 297 to placebo. Baseline characteristics were fairly similar between the two arms. Approximately 73% had undergone cardioversion and 10% had manifested at least two episodes of AF within 6 months; the rest had both features. Approximately 14% had congestive heart failure (CHF), 5% had prior stroke, and 12% had coronary artery disease. The baseline heart rate was 64 bpm. Early study drug termination due to gastrointestinal intolerance was similar between the two arms (2.0% vs. 2.7% patients, respectively).

The primary endpoint of survival free of AF was similar between n-3 PUFA and placebo arms (23.9% vs. 18.9%; hazard ratio 1.28, 95% confidence interval 0.77-1.89, p = 0.17). Other endpoints were similar including all-cause mortality (1.4% vs. 1.7%), all-cause hospitalization (16.6% vs. 14.1%), and the composite endpoint (5.5% vs. 6.7%) (p > 0.05 for all).


The results of the FORWARD trial indicate that omega-3 supplementation with 1 g daily of n-3 PUFA is not superior to placebo in patients with mostly persistent AF in maintaining NSR. This is one of the larger trials on this topic and adds to the body of literature on the utility (or lack thereof) of omega-3 in preventing recurrent AF. The totality of evidence seems to suggest no overall benefit. Longer-term follow-up of the current trial is necessary.


Macchia A, Grancelli H, Varini S, et al. 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. J Am Coll Cardiol 2012;Dec 19:[Epub ahead of print].

Presented by Dr. Alejandro Macchia at the American Heart Association Scientific Sessions, Los Angeles, CA, November 5, 2012.

Keywords: Stroke, Secondary Prevention, Fish Oils, Fatty Acids, Omega-3, Electric Countershock, Heart Failure, Atrial Fibrillation, Heart Rate, Eicosapentaenoic Acid

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