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

Circulation
Q1
Nov 2005
Citations:395
Influential Citations:24
Interventional (Human) Studies
81
S2 IconPDF Icon

Enhanced Details

Methods
Randomized, double-blind, placebo-controlled multicenter trial conducted at 18 US centers; 402 adults with implanted cardioverter-defibrillators at high risk for fatal ventricular arrhythmias; mean age 65.7 years; 84.5% male; follow-up 12 months; primary endpoint: time to first VT/VF event or death; intention-to-treat analyses.
Intervention
Fish oil (n-3 fatty acids EPA+DHA) 2.6 g daily, delivered as four 1.0-g gelatin capsules of ethyl ester concentrate; duration 12 months; taken orally. Olive oil capsules identical in appearance served as placebo for 12 months.
Results
Fish oil reduced risk of VT/VF or death compared with olive oil. In intention-to-treat analysis using confirmed events only, time to first event favored fish oil (HR 0.72; 95% CI 0.51–1.01; P=0.057). Including probable events yielded a significant risk reduction (HR 0.69; 95% CI 0.49–0.97; P=0.033). Among participants adherent for at least 11 months, risk reduction was stronger (HR 0.62; 95% CI 0.39–0.97; P=0.034); multivariate adjustment further lowered HR (0.52–0.67; P=0.006–0.037). Overall, although the primary endpoint did not reach statistical significance, regular daily fish oil intake may significantly reduce potentially fatal ventricular arrhythmias in high-risk ICD patients and could be a safer alternative to antiarrhythmic drugs.
Limitations
35% noncompliance with supplementation; difficulties obtaining complete electrograms and ICD data; missing follow-up for some participants; reliance on probable events when electrograms unavailable; ICD storage limitations may affect event ascertainment; mid-study changes (extended follow-up to 12 months for all; primary endpoint changed from number of events to time-to-first-event) may affect interpretation; limited power for detecting interactions across subgroups; generalizability beyond ICD patients remains uncertain.

Abstract

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 hypothe...