Fish oil and postoperative atrial fibrillation: The omega-3 fatty acids for prevention of post-operative atrial fibrillation (OPERA) randomized trial

OPERA Investigators

Research output: Contribution to journalArticle

147 Citations (Scopus)

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 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 ≥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 majoradverse 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%] vs224 [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.

Original languageEnglish (US)
Pages (from-to)2001-2011
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume308
Issue number19
DOIs
StatePublished - Nov 21 2012
Externally publishedYes

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Fish Oils
Omega-3 Fatty Acids
Atrial Fibrillation
Placebos
Thoracic Surgery
Atrial Flutter
Patient Acceptance of Health Care
Hemorrhage
Electric Countershock
Argentina
Italy
Capsules
Esters
Randomized Controlled Trials
Odds Ratio
Outcome Assessment (Health Care)
Morbidity
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{bf39452e281c43759f8a296710b21877,
title = "Fish oil and postoperative atrial fibrillation: The omega-3 fatty acids for prevention of post-operative atrial fibrillation (OPERA) randomized trial",
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 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 ≥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 majoradverse 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{\%}] vs224 [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.",
author = "{OPERA Investigators} and Dariush Mozaffarian and Roberto Marchioli and Alejandro Macchia and Silletta, {Maria G.} and Paolo Ferrazzi and Gardner, {Timothy J.} and Roberto Latini and Peter Libby and Federico Lombardi and O'Gara, {Patrick T.} and Page, {Richard L.} and Luigi Tavazzi and Gianni Tognoni and Massimo Santini and Albert, {Christine M.} and Maggioni, {Aldo P.} and Murray, {Katherine T.} and William Harris and Saffitz, {Jeffery E.} and David Siscovick and Phyllis Stein and Domenico Corradi and Serge Masson and Brown, {Nancy J.} and Ely, {E. Wesley} and Jackson, {James C.} and Ayumi Shintani and Milne, {Ginger L.} and Xiaoling Song and Sellke, {Frank W.} and Raffaella Pioggiarella and Lorenzo Marfisi and King, {Sarah L.} and Mills, {Kristen E.} and Adeyemi Ogunleye and Schelling, {Namasha H.} and Jason Wu and Caterina Simon and Maria Iascone and Riccardo Sinatra and Umberto Benedetto and Lorella Dreas and Aneta Aleksova and Mauro Rinaldi and Stefano Salizzoni and Giovanni Marchetto and Mauro Lamarra and Marco Pagliaro and Jori, {Maria Cristina} and Luca Dozza",
year = "2012",
month = "11",
day = "21",
doi = "10.1001/jama.2012.28733",
language = "English (US)",
volume = "308",
pages = "2001--2011",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "19",

}

TY - JOUR

T1 - Fish oil and postoperative atrial fibrillation

T2 - The omega-3 fatty acids for prevention of post-operative atrial fibrillation (OPERA) randomized trial

AU - OPERA Investigators

AU - Mozaffarian, Dariush

AU - Marchioli, Roberto

AU - Macchia, Alejandro

AU - Silletta, Maria G.

AU - Ferrazzi, Paolo

AU - Gardner, Timothy J.

AU - Latini, Roberto

AU - Libby, Peter

AU - Lombardi, Federico

AU - O'Gara, Patrick T.

AU - Page, Richard L.

AU - Tavazzi, Luigi

AU - Tognoni, Gianni

AU - Santini, Massimo

AU - Albert, Christine M.

AU - Maggioni, Aldo P.

AU - Murray, Katherine T.

AU - Harris, William

AU - Saffitz, Jeffery E.

AU - Siscovick, David

AU - Stein, Phyllis

AU - Corradi, Domenico

AU - Masson, Serge

AU - Brown, Nancy J.

AU - Ely, E. Wesley

AU - Jackson, James C.

AU - Shintani, Ayumi

AU - Milne, Ginger L.

AU - Song, Xiaoling

AU - Sellke, Frank W.

AU - Pioggiarella, Raffaella

AU - Marfisi, Lorenzo

AU - King, Sarah L.

AU - Mills, Kristen E.

AU - Ogunleye, Adeyemi

AU - Schelling, Namasha H.

AU - Wu, Jason

AU - Simon, Caterina

AU - Iascone, Maria

AU - Sinatra, Riccardo

AU - Benedetto, Umberto

AU - Dreas, Lorella

AU - Aleksova, Aneta

AU - Rinaldi, Mauro

AU - Salizzoni, Stefano

AU - Marchetto, Giovanni

AU - Lamarra, Mauro

AU - Pagliaro, Marco

AU - Jori, Maria Cristina

AU - Dozza, Luca

PY - 2012/11/21

Y1 - 2012/11/21

N2 - 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 ≥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 majoradverse 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%] vs224 [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.

AB - 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 ≥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 majoradverse 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%] vs224 [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.

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U2 - 10.1001/jama.2012.28733

DO - 10.1001/jama.2012.28733

M3 - Article

C2 - 23128104

AN - SCOPUS:84869170925

VL - 308

SP - 2001

EP - 2011

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 19

ER -