Association between omega-3 fatty acid treatment and atrial fibrillation in cardiovascular outcome trials: a systematic review and meta-analysis
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 Conclusion While overall AF event rates were low, n-3 FA treatment is associated with increased…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Jia et al. found lower risk for AF among the five low dose omega-3 FA studies compared with risk in three higher risk studies.
“Jia et al. found lower risk for AF among the five low dose omega-3 FA studies compared with risk in three higher risk studies3.”
From Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals (2026) · cites this paper as [3]
Prior meta-analyses of omega-3 and AF included at most eight trials.
“However, these meta-analyses included at most eight trials.”
From Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals (2026) · cites this paper as [3]
Recent meta-analyses of randomized controlled trials have raised concerns that omega-3 fatty acid supplementation may increase the risk of incident atrial fibrillation, potentially in a dose-dependent manner.
“Recent meta-analyses of randomized controlled trials (RCTs) have raised concerns that omega-3 fatty acid (FA) supplementation may increase the risk of incident atrial fibrillation (AF), potentially in a dose-dependent manner.”
From Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals (2026) · cites this paper as [3]
Cites
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., Granowitz, C., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812792 · Cited by 3,317 · see citing works
Self-citationRauch, B., Schiele, R., Schneider, S., Diller, F., Victor, N., Gohlke, H., Gottwik, M., Steinbeck, G., Del Castillo, U., Sack, R., et al. (2010) · Circulation · doi:10.1161/circulationaha.110.948562 · Cited by 607 · see citing works
n–3 Fatty Acids in Patients with Multiple Cardiovascular Risk Factors
The Risk and Prevention Study Collaborative Group (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1205409 · Cited by 510 · see citing works
Bischoff-Ferrari, H. A., Vellas, B., Rizzoli, R., Kressig, R. W., da Silva, J. A. P., Blauth, M., Felson, D. T., McCloskey, E. V., Watzl, B., Hofbauer, L. C., et al. (2020) · JAMA · doi:10.1001/jama.2020.16909 · Cited by 353 · see citing works
Ballantyne, C. M., Bays, H. E., Kastelein, J. J., Stein, E., Isaacsohn, J. L., Braeckman, R. A., & Soni, P. N. (2012) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.05.031 · Cited by 342 · see citing works
Self-citationEffects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction
Kalstad, A. A., Myhre, P. L., Laake, K., Tveit, S. H., Schmidt, E. B., Smith, P., Nilsen, D. W. T., Tveit, A., Fagerland, M. W., Solheim, S., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.052209 · Cited by 311 · see citing works
Kastelein, J. J. P., Maki, K. C., Susekov, A., Ezhov, M., Nordestgaard, B. G., Machielse, B. N., Kling, D., & Davidson, M. H. (2014) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2013.10.003 · Cited by 233 · see citing works
Kowey, P. R., Reiffel, J. A., Ellenbogen, K. A., Naccarelli, G. V., & Pratt, C. M. (2010) · JAMA · doi:10.1001/jama.2010.1735 · Cited by 201 · see citing works
Effects of Omega-3 Fatty Acid Supplements on Arrhythmias
Parish, S., Mafham, M., Offer, A., Barton, J., Wallendszus, K., Stevens, W., Buck, G., Haynes, R., Collins, R., Bowman, L., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.044165 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Omega-3 and risk of atrial fibrillation: vagally-mediated double-edged sword
O'Keefe, E. L., O'Keefe, J. H., Abuissa, H., Metzinger, M., Murray, E., Franco, G., Lavie, C. J., & Harris, W. S. (2025) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2024.11.003 · Cited by 12 · see citing works
Gupta, K., Hirsch, J. R., Kalsi, J., Patel, V., Gad, M. M., & Virani, S. S. (2023) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-01079-7 · Cited by 9 · see citing works
Self-citationAbuknesha, N. R., O’Keefe, J. H., Qian, F., Tintle, N. L., Lin, Y., Sun, Y., Qian, H.-Z., Aisen, P. S., Albert, C. M., Aronson, W. J., et al. (2026) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.125.014785 · Cited by 1 · see citing works
- Authors
- Jia, X., Gao, F., Pickett, J. K., Al Rifai, M., Birnbaum, Y., Nambi, V., Virani, S. S., & Ballantyne, C. M.
- Affiliations
- Baylor College of Medicine (US)
- Michael E. DeBakey VA Medical Center (US)
- Corresponding author
- Jia, Xiaoming
- Venue
- Cardiovascular Drugs and Therapy
- Published
- 2021-05-31
- Volume
- 35
- Issue
- 4
- Pages
- 793-800
- ISSN
- 0920-3206 (ISSN-L)
- 1573-7241
- OpenAlex
- W3165493665
- Cited by
- 27
- References
- 9
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 6 · 2022: 2 · 2021: 1
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cardiovascular Drugs and Therapy (publishedVersion)
- PubMed (publishedVersion)
- eCommons - AKU (Aga Khan University) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- omega-3 fatty acids, atrial fibrillation, stroke risk, dose-response relationship, cardiovascular outcome trials, omega-3 supplementation, cardiovascular risk factors, triglyceride-rich lipoproteins, triglyceride metabolism, endothelial dysfunction, blood pressure, coagulation
- MeSH terms
- Atrial Fibrillation, Dose-Response Relationship, Drug, Humans, Fatty Acids, Omega-3, Drug Monitoring, Risk Assessment, Dietary Supplements, Stroke
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
