Abstract (as published in JAMA)
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 Postoperative 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 > or = 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.
Authors’ Conclusion: In this large multinational trial among [intensely treated] patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF.
O-3s & Atrial Fibrillation
Mozaffarian D Marchioli R Macchia A Silletta MG Ferrazzi P Gardner TJ Latini R Libby P Lombardi F O’Gara PT Page RL Tavazzi L and Tognoni G for the OPERA Investigators (2012). Fish Oil and Postoperative Atrial Fibrillation The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial. JAMA 308(19):doi:10.1001/jama.2012.28733.
Results from the current publication do not change the totality of the publicly available scientific evidence demonstrating a cardiovascular benefit of EPA and DHA in healthy populations, as well as in many populations with pre-existing cardiovascular ailments. Therefore, consumers should continue to eat fish and take their omega-3 products for heart health.
What Else Should You Know?
While very short (2-3 days only) preoperative loading of n-3 PUFAs (compared to placebo) followed postoperatively for up to ten days did not reduce the risk of postoperative AF, keep in mind that's a very specific scenario and the results should not be over-generalized. That is, it's possible that longer term consumption of n-3 PUFAs prior to surgery would be beneficial. The authors themselves suggest that long-term consumption may be the best way to see a benefit. “Our design cannot exclude potential benefits of much longer durations (e.g., weeks to years) of n-3 PUFA supplementation for altering systemic physiology and risk of AF in other clinical contexts.” Optimally, n-3 PUFAs should be consumed over a lifetime, as part of an overall healthy diet.
There were some exciting secondary findings that approached significance and clearly warrant further investigation, including the n-3 PUFA group (compared to placebo) demonstrating a decrease in in-hospital major adverse cardio events, as well as a decrease in death at 30 days. While further investigation is necessary to determine if these are chance findings, if they are not then this is an instance when clinical significance can occur in the absence of statistical significance.
Authors’ comment- “…the overall evidence from subsequent experiments, observational studies, and clinical trials continues to point toward a reduction in cardiac death as the principal cardiovascular benefit of long-term n-3-PUFA intake.”
Authors’ comment-“Many drugs have been tested but failed to prevent postoperative AF; others, such as β-blockers and amiodarone, only partly reduce risk. The effects of cardiac surgery on neuro-hormonal, oxidative, and inflammatory activation and atrial remodeling may simply be too great to be countered by most drugs, including n-3-PUFAs.”
Global Organization for EPA and DHA Omega-3s (2012). O-3s & Atrial Fibrillation [Peer commentary on the paper “Fish Oil and Postoperative Atrial Fibrillation The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial” by Mozaffarian D Marchioli R Macchia A Silletta MG Ferrazzi P Gardner TJ Latini R Libby P Lombardi F O’Gara PT Page RL Tavazzi L and Tognoni G for the OPERA Investigators (2012). JAMA 308(19):doi:10.1001/jama.2012.28733.].