• Peder L Myhre, Are A Kalstad, Sjur H Tveit, Kristian Laake, Erik B Schmidt, Pal Smith, NilsenDennis W TDWTDepartment of Cardiology, Stavanger University Hospital, Stavanger, Norway.Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway., Arnljot Tveit, Svein Solheim, Harald Arnesen, and Ingebjørg Seljeflot.
• Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
• J. Intern. Med. 2022 May 1; 291 (5): 637-647.

BackgroundThe 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.ObjectivesTo assess changes in EPA and DHA serum concentrations during n-3 PUFA supplementation and their association with incident cardiovascular events.MethodsIn 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).ResultsEPA 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).ConclusionGreater 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.© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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