Omega-3 fatty acids supplementation associated with increased risk of incident AF

Omega-3 fatty acids supplementation and risk of atrial fibrillation: an updated meta-analysis of randomized controlled trials

Literature - Lombardi M, Carbone S, Del Buono MG et al., - Eur Heart J Cardiovasc Pharmacother. 2021 Apr 28;pvab008. doi: 10.1093/ehjcvp/pvab008.

Introduction and methods

Omega-3 fatty acids (O3FA) are being utilized to reduce the risk of CV events in adults at high risk for, or with established CVD and elevated triglycerides. However, safety results of CVOTs investigating O3FA supplementation showed a higher incidence of AF events in patients taking O3FA, compared to those on placebo. This meta-analysis investigated whether O3FA supplementation, compared with placebo, is associated with an increased risk of incident AF.

Five RCTs were included in this study-level meta-analysis: REDUCE-IT, ASCEND, R&P, STRENGTH and OMEMI [1-5]. The primary endpoint of the analysis was onset of AF.

Main results

  • The random effect model showed that O3FA supplementation was associated with an increased risk of onset of AF, compared to placebo (Incidence Rate Ratio [IRR] 1.37, 95%CI 1.22-1.54, P<0.001).
  • No significant heterogeneity and no publication bias were found.


This meta-analysis of five RCTs showed that O3FA supplementation, compared to placebo, is associated with an increased risk of incident AF in patients with elevated triglycerides and at elevated CV risk.


1. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, Tardif J-C, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11–22.

2. Kromhout D, Giltay EJ, Geleijnse JM; For the AOTG. N-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 2010;363:2015–2026.

3. Roncaglioni MC, Tombesi M, Avanzini F, Barlera S, Caimi V, Longoni P, Marzona I, Milani V, Silletta MG, Tognoni G, Marchioli R; Risk and Prevention Study Collaborative Group. N-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med 2013;368:1800–1808.

4. Nicholls SJ, Lincoff AM, Garcia M, Bash D, Ballantyne CM, Barter PJ, Davidson MH, Kastelein JJP, Koenig W, McGuire DK, Mozaffarian D, Ridker PM, Ray KK, Katona BG, Himmelmann A, Loss LE, Rensfeldt M, Lundström T, Agrawal R, Menon V, Wolski K, Nissen SE. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA 2020;324:2268–2280.

5. Kalstad AA, Myhre PL, Laake K, Tveit SH, Schmidt EB, Smith P, Nilsen DWT, Tveit A, Fagerland MW, Solheim S, Seljeflot I, Arnesen H; OMEMI Investigators. Effects of n-3 fatty acid supplements in elderly patients after myocardial infarction: a randomized controlled trial. Circulation 2020.

Find this article online at Eur Heart J Cardiovasc Pharmacother.

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