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

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.