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Association Between Omega-3 Fatty Acid Treatment and Atrial Fibrillation in Cardiovascular Outcome Trials: A Systematic Review and Meta-Analysis.

Jia X, Gao F, Pickett JK, Al Rifai M, Birnbaum Y, Nambi V, Virani SS, Ballantyne CM. Association Between Omega-3 Fatty Acid Treatment and Atrial Fibrillation in Cardiovascular Outcome Trials: A Systematic Review and Meta-Analysis. Cardiovascular drugs and therapy. 2021 Aug 1; 35(4):793-800.

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PURPOSE: Data on the relationship between omega-3 fatty acid (n-3 FA) therapy with atrial fibrillation (AF) have been inconsistent. We investigate the association between n-3 FA and risk for AF by pooling data from available large, cardiovascular outcome trials. METHODS: We performed a systematic search on PubMed and Embase for studies on n-3 FA with AF as an outcome measure. Large ( = 1000 participants) randomized controlled trials with? = 1-year follow-up period were included. The association between n-3 FA and risk of AF or stroke was assessed. Mantel-Haenszel random effects model was used to calculate risk ratios (RR) with 95% confidence intervals (CI). We then performed meta-regression to evaluate effect on AF by dose of n-3 FA therapy. RESULTS: A total of 8 randomized control trials encompassing 83,112 participants were included in the meta-analysis. Of these, five trials assessed a lower dose of n-3 FA ( = 1 g daily, n? = 61,096) while 3 trials assessed a higher dose ( > 1 g daily, n? = 22,016). In meta-analysis, a significant association was noted between n-3 FA treatment and risk of AF (4.0% vs 3.3%; RR 1.24, 95% CI 1.11-1.38, p? = 0.0002). There was a modest but still significant association in the lower dose (n-3 FA? = 1 g daily) sub-group (RR 1.12, 95% CI 1.04-1.21, p? = 0.004) and stronger association in the higher dose (n-3 FA? > 1 g daily) sub-group (RR 1.51, 95% CI 1.26-1.80, p? < 0.001; p-interaction between low versus high subgroups? = 0.003). There was no increase in stroke risk (RR 1.04, 95% CI 0.90-1.20). Meta-regression demonstrated a significant association between dose of n-3 FA with risk for AF events (log RR 0.103, 95% CI 0.048-0.159, p? < 0.001). CONCLUSION: While overall AF event rates were low, n-3 FA treatment is associated with increased risk for AF.

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