Fish Oil and Postoperative Atrial Fibrillation：Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial

Dariush Mozaffarian, MD, DrPH; Roberto Marchioli, MD; Alejandro Macchia, MD; Maria G. Silletta, MS; Paolo Ferrazzi, MD; Timothy J. Gardner, MD; Roberto Latini, MD; Peter Libby, MD; Federico Lombardi, MD; Patrick T. O’Gara, MD; Richard L. Page, MD; Luigi Tavazzi, MD; Gianni Tognoni, MD; for the OPERA Investigators

JAMA. 2012;308(19):2001-2011. doi:10.1001/jama.2012.28733.

ABSTRACT
Context  Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results.

Objective  To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF.

Design, Setting, and Patients  The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment.

Intervention  Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first.

Main Outcome Measure  Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events.

Results  At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events.

Conclusion  In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF.