High-Dose Marine Omega-3s Raise Risk for Atrial Fibrillation

This transcript has been edited for clarity.

Hello. This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital.

I'd like to talk with you about a recent report in Circulation: a meta-analysis of randomized clinical trials of the marine omega-3 fatty acids and risk for atrial fibrillation (AF). The report was led by Dr Baris Spencer from Geneva, Switzerland, and by Dr Christine Albert at Cedars-Sinai Medical Center. I'd like to acknowledge that I was also a co-author of this report and that it included the vitamin D and omega-3 trial VITAL, of which I am a principal investigator, and Dr Christine Albert is the principal investigator of the ancillary study, Vital Rhythm, which included AF endpoints.

This meta-analysis included seven large-scale randomized clinical trials of the marine omega-3s and where they had ascertained AF endpoints. Four of the trials were testing relatively low doses of the marine omega-3s (< 1 g/day), and three of the trials tested high-dose omega-3s (> 1 g/day). In the lower-dose category were the VITAL trial, the GISSI heart failure trial, and the ASCEND trials. The higher-dose category included the REDUCE-IT and STRENGTH trials.

These seven trials, which included more than 81,000 participants, found that the risk for AF was elevated with the omega-3s, with a hazard ratio of 1.25. That was strongly statistically significant, but there was also evidence of a dose response. The trials had tested lower doses (< 1 g/day) and, individually, they did not show a significant increase in AF. In aggregate, however, there was a 12% increase in AF risk. In the high-dose (> 1 g/day) trials, there was a 49%-50% risk. In a dose-response gradient analysis, for each 1 g increase in the dose of the omega-3s, there was an 11% increase in the risk for AF — a strongly significant interaction.