Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 34 Trials including 114,326 Individuals

Background: Recent meta-analyses of randomized controlled trials (RCTs) have raised concerns that treatment with omega-3 fatty acids may increase risk of atrial fibrillation (AF). However, these meta-analyses included at most eight trials. The aim of this current meta-analysis was to expand the search by including other eligible omega-3 RCTs with AF incidence data, incorporating both published and unpublished data. Methods: Eligible studies were RCTs investigating daily doses of ≥500 mg/d of docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). Additional inclusion criteria included ≥12 months treatment with EPA/DHA, participants ≥ 50 years of age, and where possible, the absence of known AF/atrial flutter at baseline. The primary outcome was occurrence of new-onset AF. Our primary hypothesis was that risk for AF would simultaneously depend on both omega-3 dose (above or below 1500 mg/d) and background cardiovascular disease (CVD) risk status, and that their combined impact on AF risk would be synergistic. Results: A total of 34 RCTs (36 datasets; n=114,326) were included in this meta-analysis. Only studies including patients at high-risk for CVD who were treated with high-doses of EPA/DHA (>1500 mg/day) showed a statistically significant increase in AF risk with a pooled odds ratio (OR) of 1.48 (95% CI, 1.21-1.81) and an absolute risk difference of 0.8% (0.40-1.1%). None of the other three groups showed statistically significant levels of AF risk (ORs 1.07 (high risk, low dose), 1.06 (low risk, low dose) and 0.95 (low risk, high dose). Conclusion: This meta-analysis suggests that treatment with EPA/DHA is most likely to increase risk for AF in patients at high-risk for CVD who are treated with high doses of EPA/DHA. The risk for AF should be balanced against the benefits of EPA/DHA in making treatment decisions.