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

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Abstract

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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Author information

Authors and Affiliations

  1. Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Xiaoming Jia, June K. Pickett, Mahmoud Al Rifai, Yochai Birnbaum, Vijay Nambi, Salim S. Virani & Christie M. Ballantyne

  2. Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Feng Gao

  3. Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA

    Vijay Nambi & Salim S. Virani

  4. Health Services Research and Development Center for Innovations in Quality Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA

    Salim S. Virani

  5. Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Salim S. Virani

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  1. Xiaoming Jia
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Contributions

Xiaoming Jia: conceptualization, methodology, and writing—original draft; Feng Gao: methodology and writing—original draft; Mahmoud Al Rifai: writing—review and editing; June K. Pickett: writing—review and editing; Yochai Birnbaum: writing—review and editing; Vijay Nambi: writing—review and editing; Salim S. Virani: writing—review andediting; Christie M. Ballantyne: writing—review and editing.

Corresponding author

Correspondence to Xiaoming Jia.

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Competing Interests

Xiaoming Jia, Feng Gao, Mahmoud Al Rifai, and June K. Pickett have nothing to disclose.

Christie M. Ballantyne: Grant/research support (paid to institution, not individual), Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron. Consultant: Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Esperion, Genentech, Gilead, Matinas BioPharma Inc., New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi-Synthelabo.

Yochai Birnbaum: Research grant AstraZeneca.

Vijay Nambi: Site PI study sponsored by Merck, Amgen. Provisional patent with Roche for use of biomarkers in prediction of heart failure.

Salim S. Virani: Honorarium, American College of Cardiology (Associate Editor for Innovations, acc.org); Steering Committee, Patient and Provider Assessment of Lipid Management (PALM registry) at the Duke Clinical Research Institute (no financial remuneration).

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Jia, X., Gao, F., Pickett, J.K. et al. Association Between Omega-3 Fatty Acid Treatment and Atrial Fibrillation in Cardiovascular Outcome Trials: A Systematic Review and Meta-Analysis. Cardiovasc Drugs Ther 35, 793–800 (2021). https://doi.org/10.1007/s10557-021-07204-z

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