title: The ω-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial--rationale and design.
abstract: Postoperative atrial fibrillation/flutter (PoAF) commonly complicates cardiac surgery, occurring in 25% to 60% of patients. Postoperative atrial fibrillation/flutter is associated with significant morbidity, higher long-term mortality, and increased health care costs. Novel preventive therapies are clearly needed. In experiments and short-term trials, seafood-derived long-chain ω-3 polyunsaturated fatty acids (PUFAs) influence several risk factors that might reduce risk of PoAF. A few small and generally underpowered trials have evaluated effects of ω-3-PUFAs supplementation on PoAF with mixed results. The OPERA trial is an appropriately powered, investigator-initiated, randomized, double-blind, placebo-controlled, multinational trial to determine whether perioperative oral ω-3-PUFAs reduces occurrence of PoAF in patients undergoing cardiac surgery. Additional aims include evaluation of resource use, biologic pathways and mechanisms, postoperative cognitive decline, and safety. Broad inclusion criteria encompass a "real-world" population of outpatients and inpatients scheduled for cardiac surgery. Treatment comprises a total preoperative loading dose of 8 to 10 g of ω-3-PUFAs or placebo divided over 2 to 5 days, followed by 2 g/d until hospital discharge or postoperative day 10, whichever comes first. Based on anticipated 30% event rate in controls, total enrollment of 1,516 patients (758 per treatment arm) will provide 90% power to detect 25% reduction in PoAF. The OPERA trial will provide invaluable evidence to inform biologic pathways; proof of concept that ω-3-PUFAs influence cardiac arrhythmias; and potential regulatory standards and clinical use of this simple, inexpensive, and low-risk intervention to prevent PoAF.
authors: Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. dmozaffa@hsph.harvard.edu
authors: Dariush
authors: D
authors: Mozaffarian
authors: Roberto
authors: R
authors: Marchioli
authors: Tim
authors: T
authors: Gardner
authors: Paolo
authors: P
authors: Ferrazzi
authors: Patrick
authors: P
authors: O'Gara
authors: Roberto
authors: R
authors: Latini
authors: Peter
authors: P
authors: Libby
authors: Federico
authors: F
authors: Lombardi
authors: Alejandro
authors: A
authors: Macchia
authors: Richard
authors: R
authors: Page
authors: Massimo
authors: M
authors: Santini
authors: Luigi
authors: L
authors: Tavazzi
authors: Gianni
authors: G
authors: Tognoni
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000601:surgery; D006801:Humans; D011183:Postoperative Complications; D016896:Treatment Outcome
chemical_list: D015525:Fatty Acids, Omega-3