Comparative efficacy of omega-3 polyunsaturated fatty acids on major cardiovascular events: A network meta-analysis of randomized controlled trials

Prog Lipid Res. 2022 Nov:88:101196. doi: 10.1016/j.plipres.2022.101196. Epub 2022 Oct 28.


The role of omega-3 polyunsaturated fatty acids (PUFAs) in primary and secondary prevention on major cardiovascular events (MCE) is inconclusive due to the potential heterogeneity in study designs of formulas, dosages, and ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the findings of previous randomized controlled trials (RCTs). Here we conducted a comprehensive narrative review of pre-clinical studies and updated a network meta-analysis (NMA) to determine the comparative efficacy against MCE with different EPA/DHA dosages and formulas. We found that pure EPA was ranked the best option in the secondary prevention (hazard ratio: 0.72, 95% confidence interval: 0.65 to 0.81) from the NMA of 39 RCTs with 88,359 participants. There was no evidence of omega-3 PUFAs' efficacy in primary prevention. The mechanisms of omega-3 PUFAs' cardiovascular protection might link to the effects of anti-inflammation and stabilization of endothelial function from PUFA's derivatives including eicosanoids and the special pre-resolving mediators (SPMs).

Keywords: Cardiovascular disease; Major cardiovascular events; Network meta-analysis; Omega-3.

Publication types

  • Meta-Analysis
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / prevention & control
  • Docosahexaenoic Acids / pharmacology
  • Docosahexaenoic Acids / therapeutic use
  • Eicosapentaenoic Acid / pharmacology
  • Fatty Acids, Omega-3* / pharmacology
  • Fatty Acids, Omega-3* / therapeutic use
  • Humans
  • Network Meta-Analysis
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Fatty Acids, Omega-3
  • Eicosapentaenoic Acid
  • Docosahexaenoic Acids