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JAMA. 2012 Nov 21;308(19):2001-11.

Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial.

Collaborators (189)

Marchioli R, Mozaffarian D, Gardner TJ, Ferrazzi P, O'Gara PT, Macchia A, Santini M, Tavazzi L, Tognoni G, Page RL, Lombardi F, Albert CM, Maggioni AP, Murray KT, Latini R, Libby P, Harris B, Saffitz JE, Siscovick D, Stein P, Corradi D, Masson S, Brown NJ, Ely E, Jackson JC, Shintani A, Milne GL, Song X, Sellke FW, Silletta MG, Pioggiarella R, Marfisi L, King SL, Mills KE, Ogunleye A, Schelling NH, Wu J, Ferrazzi P, Simon C, Iascone M, Sinatra R, Benedetto U, Dreas L, Aleksova A, Rinaldi M, Salizzoni S, Marchetto G, Lamarra M, Pagliaro M, Jori MC, Dozza L, Calvi S, Casabona R, Zingarelli E, Flocco R, Eusebio A, Raffa G, Tarelli G, Parolari A, Cavallotti L, Miyasoedova V, Laguzzi F, Gregorini R, Mangia F, Gazzoli F, Raviola E, Viganò M, Livi U, Pompei E, Salvador L, Lamascese N, Bilotta M, Martinelli L, Cannata A, Brown NJ, Byrne J, Leacche M, Petracek MR, Ball SK, Jessen ME, Weyant M, Damiano RJ Jr, Sellke FW, Singh AK, McDonald MJ, Bolman R 3rd, Conboy DA, Burgess A, Puskas JD, VanderWoude J Jr, Bell MC, Sethi G, Lee DC, Favaloro RR, Hershson AR, Figal JC, Domenech A, Halac M, Nicolosi LN, Morós CG, Rubio Mdel C, Suárez RF, Cacheda H, Casal JP, Medrano JC, Cucurell MC, Scattini F, Nojek C, Camporrotondo M, Mozaffarian, Silletta, Scarano M, Herrington DM, Brooks MM, De Caterina R, Gillinov M, Padeletti L, Pellegrini F, Rothschild BB, Rubinstein F, Diep PQ, Guzman JB, Palmarini L, Sacchetti S, Flamminio AV, Marfisi R, Scarano M, Afshin A, Huang H, Otite F, Ambrosio M, Lincesso A, Pezzoli L, Anzini M, Carriere C, Belfiore R, Fortunato G, Pellegrini A, Raviola E, Reale V, Sorrentino P, Schiavina G, Negrosanti M, Ravenni G, Moro F, Brambilla M, Nava C, Giroli M, Daprati A, Gennari M, Cusihuaman DE, Spagnolo B, Francia M, Stanca M, Paris M, Berwick D, Lusona B, Castiglione N, De Biasio M, Daffarra C, Ahmad R, Meisch CA, Maltais S, Balaguer J, Donahue T, Guyton RA, Thourani V, Halkos M, Lattouf O, Baio KT, Levine SR, Pitts ZE, Janssen K, Ruhlman M, Sharp S, Pang K, Mungo MN, Servián AL, Battellini R, Marenchino R, Kotowicz V, Cesáreo V, Sánchez R, Romero V, Avila S, Donnini F, Biancospino L, Laurino R, Portalea R.

Author information

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Erratum in

  • JAMA. 2013 Mar 6;309(9):876.



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.


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


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.


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.


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.


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.


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. TRIAL REGISTRATION Identifier: NCT00970489.

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