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  • Erica S. Zado
    Corresponding Author: Erica S. Zado, PA-C, FHRS, Cardiovascular Division Founders 9 Hospital of the University of Pennsylvania 3400 Spruce Street Philadelphia, PA 19104
    The Section of Cardiac Electrophysiology, Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, PA
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Published:November 10, 2021DOI:
      There has been conflicting data regarding whether supplementation with omega 3 fatty acids increases the risk of atrial fibrillation (AF). The investigators (Gencer et al. Circulation 2021; online ahead of print. PMID: 34612056) sought to answer the question of whether use of omega 3 fatty acid increases risk of AF and to assess whether the dose of supplementation has an effect, through the use of meta-analysis of randomized trials. Following PRISMA guidelines for meta-analysis, the investigators searched databases for randomized, controlled, double-blind trials of omega 3 supplements versus placebo. The included studies needed to have at least 500 participants with a minimum follow-up of at least 1 year. From just over 4000 studies screened, 7 studies with 81,210 patients were included in this meta-analysis. Using a number of statistical techniques, these 7 trials were assessed in detail for aggregate results. Of these 7 trials, 5 trials with 58,939 (72.6%) patients studied lower dose (<1 gram/day) fatty acid supplements and the other 2 with 22,271 participants (27.4%) tested >1 gram/day. The mean age was 65.1 years with 39.2% female and median follow-up 4.9 years. AF occurred in 2,905 (3.6%) of patients included in the meta-analysis with a pooled hazard ratio of 1.25 (95% confidence interval 1.07-1.46, P=0.013). The pooled hazard ratio was higher in the high dose trials (>1 gram/day) at 1.25 (95% confidence interval 1.04-2.15, P=0.042) than in the low dose (<1 gram/day) trials (HR 1.12 with 95% confidence interval 1.03-1.22, P=0.024). In meta-regression analysis, the hazard ratio for risk of AF with every 1-gram increase in omega 3 fatty acid per day was 1.11, meaning that for every gram/day increase, there is 11% increase in risk of AF. The authors note a number of limitations including that no trial directly compared high versus low dose, different doses and formulations were used among the trials, and given the methodology used, subgroup analysis based on age and other clinical characteristics was not possible. Additionally, trial participants may not be similar to real-life users of omega 3 fatty acid supplements. The authors conclude that in this meta-analysis of 7 randomized controlled trials, omega 3 fatty acid supplements were associated with an increased risk of AF and the risk was greatest at a dose >1 gram/day.
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