The ω-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial--rationale and design

Am Heart J. 2011 Jul;162(1):56-63.e3. doi: 10.1016/j.ahj.2011.03.035. Epub 2011 Jun 12.

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.

Trial registration: ClinicalTrials.gov NCT00970489.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / prevention & control*
  • Cardiac Surgical Procedures / adverse effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Fatty Acids, Omega-3 / administration & dosage*
  • Follow-Up Studies
  • Heart Diseases / surgery
  • Humans
  • Postoperative Complications
  • Treatment Outcome

Substances

  • Fatty Acids, Omega-3

Associated data

  • ClinicalTrials.gov/NCT00970489