Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation - OPERA


Data on the role of omega-3 supplementation in preventing postoperative atrial fibrillation (AF) (primary prevention) have been mixed. The current trial sought to compare the efficacy of 2 g daily of n-3 polyunsaturated fatty acid (PUFA) for the maintenance of normal sinus rhythm in patients undergoing cardiac surgery.


Omega-3 supplementation with 2 g daily of n-3 PUFA would reduce postoperative AF in patients undergoing cardiac surgery.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Age ≥18 years
  • Planned cardiac surgery after ≥1 day
  • Normal sinus rhythm on screening electrocardiogram (ECG)

    Number of screened applicants: 3,154
    Number of enrollees: 1,516
    Duration of follow-up: 30 days
    Mean patient age: 63.7 years
    Percentage female: 28%
    Ejection fraction: 56.7%
    New York Heart Association class: II (13.5%), III (9%), IV (1.4%)


  • Lack of normal sinus rhythm on screening ECG
  • Regular use of fish oil
  • Known allergy to fish or olive oil
  • Existing or planned cardiac transplant or use of ventricular assist device
  • Pregnancy

Primary Endpoints:

  • Occurrence of postoperative AF of at least 30 seconds in duration and documented by rhythm strip or 12-lead ECG

Secondary Endpoints:

  • Postoperative AF that was sustained (>1 hour), symptomatic, or treated with pharmacological or electrical cardioversion
  • Postoperative AF excluding atrial flutter
  • Time to first postoperative AF
  • Number of postoperative AF episodes per patient

Drug/Procedures Used:

Patients were randomized in a 1:1 fashion to either 2 g daily of n-3 PUFA (containing at least 840 mg of eicosapentaenoic acid [EPA] [approximately 465 mg] plus docosahexaenoic acid [DHA] [approximately 375 mg] as ethyl esters (Omacor; Pronova Bio-Pharma, Norway) or matching placebo (olive oil). Preoperative loading was done with 10 g of n-3 PUFA divided over 3-5 days (or 8 g over 2 days). Following cardiac surgery, patients received 2 g/d until hospital discharge or postoperative day 10, whichever occurred sooner.

Concomitant Medications:

  • Preoperative: Amiodarone (4%), beta-blockers (58%), statins (57%), antiplatelets or anticoagulants (61%), other antiarrhythmic agents (2%)
  • Postoperative: beta-blockers (76.9%), amiodarone (36.9%)

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 8% had a history of AF and 0.8% of ventricular tachycardia/ventricular fibrillation. Valve surgery was planned in 52% (73% aortic) and the mean EuroSCORE was 3.7. The mean left atrial diameter was 4.2 mm.

The primary endpoint of any first postoperative AF was similar between n-3 PUFA and placebo arms (30.0% vs. 30.7%; hazard ratio 0.96, 95% confidence interval 0.77-1.20, p = 0.74). Other endpoints including sustained, symptomatic, or treated AF were similar (29.6% vs. 30.5%, p = 0.70), number of postoperative episodes (p = 0.73), in-hospital major adverse cardiac events (1.7% vs. 2.6%, p = 0.18), 30-day all-cause mortality (1.1% vs. 2.0%, p = 0.14), 30-day arterial thromboembolism (0.7% vs. 1.7%, p = 0.047), and total length of stay (7 vs. 7, p = 0.48) were similar between the two arms.

Need for red blood cell transfusions during hospitalization (p < 0.0001) was lower in the n-3 PUFA arm, while minor adverse events commonly seen with fish oil, such as gastrointestinal upset, burping, and fish oil taste, occurred more commonly in the n-3 PUFA group. Other adverse events requiring study drug discontinuation were also similar between the two arms.


The results of the OPERA trial indicate that omega-3 supplementation with 10 g loading followed by 2 g daily of n-3 PUFA is not superior to placebo in preventing postoperative AF in patients undergoing cardiac surgery. This is the largest trial on this topic, and mirrors other recent data on lack of efficacy with omega-3 supplementation on AF prevention (both primary and secondary). These data are clinically relevant since many basic science studies have demonstrated antiarrhythmic effects with omega-3 supplementation. Longer-term follow-up of the current trial is necessary to ascertain possible benefits beyond 30 days in selected patients.


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

Mozaffarian D, Marchioli R, Macchia A, et al., on behalf of the OPERA Investigators. Fish Oil and Postoperative Atrial Fibrillation: The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial. JAMA 2012;Nov 5:[Epub ahead of print].

Keywords: Follow-Up Studies, Erythrocyte Transfusion, Ventricular Fibrillation, Electrocardiography, Eicosapentaenoic Acid, Primary Prevention, Length of Stay, Thromboembolism, Tachycardia, Ventricular, Docosahexaenoic Acids, Fatty Acids, Omega-3, Plant Oils, Esters, Confidence Intervals, Cardiac Surgical Procedures, Coronary Artery Bypass, Taste

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