Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial

J Intern Med. 2022 May;291(5):637-647. doi: 10.1111/joim.13442. Epub 2022 Jan 4.


Background: The cardiovascular benefit from n-3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear.

Objectives: To assess changes in EPA and DHA serum concentrations during n-3 PUFA supplementation and their association with incident cardiovascular events.

Methods: In the OMEMI trial, elderly patients with a recent AMI were randomized to 1.8 g/day of EPA/DHA or control (corn oil) for 2 years. The primary outcome was a composite of AMI, coronary revascularization, stroke, heart failure hospitalization, or all-cause death (major adverse cardiovascular event [MACE]) and the secondary outcome was new-onset atrial fibrillation (AF).

Results: EPA and DHA measurements were available in 881 (92% of survivors) participants at randomization and study completion. EPA and DHA increased in the active treatment arm (n = 438) by a median of 87% and 16%, respectively. Greater on-treatment increases in EPA and DHA were associated with decreasing triglycerides, increasing high-density lipoprotein cholesterol, and lower baseline EPA and DHA concentrations. Greater on-treatment increases in EPA were associated with lower risk of MACE (adjusted hazard ratio 0.86 [95% confidence interval, CI, 0.75-0.99], p = 0.034), and higher risk of AF (adjusted hazard ratio (HR) 1.36 [95% CI 1.07-1.72], p = 0.011). Although there were similar tendencies for DHA changes and outcomes, these associations were not statistically significant (HR 0.84 [0.66-1.06] for MACE and 1.39 [0.90-2.13] for AF).

Conclusion: Greater on-treatment increases in EPA were associated with lower risk of MACE and higher risk of new-onset AF. These data suggest that the cardiovascular effects of increasing n-3 PUFA levels through supplements are complex, involving both potential benefits and harm.

Keywords: atrial fibrillation; cardiovascular events; docosahexaenoic acid; eicosapentaenoic acid; omega-3.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrial Fibrillation* / drug therapy
  • Dietary Supplements
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid / pharmacology
  • Eicosapentaenoic Acid / therapeutic use
  • Fatty Acids, Omega-3* / therapeutic use
  • Humans
  • Myocardial Infarction* / epidemiology


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