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Circulation. 2005;112:2762-2768
doi: 10.1161/CIRCULATIONAHA.105.549527
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(Circulation. 2005;112:2762-2768.)
© 2005 American Heart Association, Inc.


Arrhythmia/Electrophysiology

Prevention of Fatal Arrhythmias in High-Risk Subjects by Fish Oil n-3 Fatty Acid Intake

Alexander Leaf, MD; Christine M. Albert, MD, MPH; Mark Josephson, MD; David Steinhaus, MD; Jeffrey Kluger, MD; Jing X. Kang, MD, PhD; Benjamin Cox, BS; Hui Zhang, PhD; David Schoenfeld, PhD, for the Fatty Acid Antiarrhythmia Trial Investigators*

From the Department of Medicine (A.L., J.X.K., B.C., Fatty Acid Antiarrhythmia Trial Investigators), Massachusetts General Hospital and Harvard Medical School, Boston, Mass; Cardiovascular Division (C.M.A.), Department of Medicine, Massachusetts General Hospital, and the Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Mass; Division of Cardiology (M.J.), Beth Israel–Deaconess Medical Center and Harvard Medical School, Boston, Mass; Mid-America Heart Institute (D. Steinhaus), St. Luke’s Hospital, Kansas City, Mo; Arrhythmia/ICD Clinic (J.K.), Hartford Hospital, Hartford, Conn; and Biostatistics Center (H.Z., D. Schoenfeld), Department of Medicine, Massachusetts General Hospital and Harvard School of Public Health, Boston, Mass.

Correspondence to Alexander Leaf, MD, Massachusetts General Hospital, E 149 13th St, Charlestown, MA 02129. E-mail aleaf{at}partners.org

Received March 15, 2005; revision received July 13, 2005; accepted July 15, 2005.

Background— The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a randomized trial of post–myocardial infarction patients. Therefore, we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients.

Methods and Results— Four hundred two patients with implanted cardioverter/defibrillators (ICDs) were randomly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months. The primary end point, time to first ICD event for ventricular tachycardia or fibrillation (VT or VF) confirmed by stored electrograms or death from any cause, was analyzed by intention to treat. Secondary analyses were performed for "probable" ventricular arrhythmias, "on-treatment" analyses for all subjects who had taken any of their oil supplements, and "on-treatment" analyses only of those subjects who were on treatment for at least 11 months. Compliance with double-blind treatment was similar in the 2 groups; however, the noncompliance rate was high (35% of all enrollees). In the primary analysis, assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause (risk reduction of 28%; P=0.057). When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P=0.033. For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P=0.034).

Conclusions— Although significance was not achieved for the primary end point, this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias, regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias.


Key Words: fatty acids • cardioversion • arrhythmia • death, sudden • heart arrest




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