Omega-3 fatty acid supplements and risk of atrial fibrillation and 'micro-atrial fibrillation': A secondary analysis from the OMEMI trial

Abstract

Background & aims: Recent randomized clinical trials have raised concerns regarding potential off target adverse effects from supplementation of n-3 polyunsaturated fatty acids (PUFA) on atrial fibrillation (AF) risk. We aimed to assess risk and potential mediators of AF and 'micro-AF' from n-3 PUFA in post-myocardial infarction (MI) patients.

Methods: In the OMEMI trial, 70-82 y. o. patients with a recent MI were randomized to 1.8 g/day of eicosapentaenoic-/docosahexaenoic acid (EPA/DHA) or placebo (corn oil) for two years. New-onset AF and 'micro-AF' was recorded by clinical detection and by screening with Zenicor thumb-ECG (adjudicated by blinded investigators). Serum EPA and DHA were measured at baseline and study end.

Results: At baseline, 759 of 1014 (75%) patients had no AF history. These patients were aged 75 ± 4 years and 71% were male. During follow-up, 43 patients developed new-onset AF (39 clinically-detected and 4 by thumb-ECG screening). In addition, 27 patients had episodes of micro-AF, yielding a total of 70 patients with new-onset AF or 'micro-AF'. In the n-3 PUFA group 46 (11.9%) had AF/'micro-AF' (28 AF, 18 'micro-AF') and in the placebo group 24 (6.5%) had AF/micro-AF (15 AF, 9 micro-AF); HR 1.90 (95%CI 1.16-3.11), P = 0.011. Changes in serum EPA (but not DHA) mediated the effect from n-3 PUFA on AF risk, explaining 65% of the association.

Conclusion: Supplementation of n-3 PUFA post MI increases the risk of 'micro-AF' and AF, and increases in EPA seems to be an important mediator of the treatment effect from n-3 PUFA on the risk of AF.

Study registration: OMEMI Study; ClinicalTrails.gov identifier: NCT0184194.

Keywords: Atrial fibrillation; Docosahexaenoic acid; Eicosapentaenoic acid; Omega-3 PUFA.