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Fish Oils Fail to Impact Endpoints in AF


The recent AFFORD trial suggests no clinical role for omega-3 fatty acids in preventing atrial fibrillation or in modulating disease markers.

The pathogenesis of atrial fibrillation (AF) is multifactorial and includes inflammation and oxidative stress. Fish oils, which possess intrinsic antiarrhythmic properties, also can have a beneficial effect on inflammation. Results of trials to date that examined the use of fish oil for the prevention of AF, however, have been mixed.

Most recently, the AFFORD trial, published in the Journal of the American College of Cardiology in October 2014, demonstrated that high-dose omega-3 fatty acids do not reduce AF recurrence or inflammation or oxidative stress markers. 

The AFFORD trial was a double-blind, randomized, placebo-controlled trial of 337 patients with symptomatic paroxysmal or persistent AF within 6 months of enrollment. Participants were randomized to receive 4 g/d of fish oil or placebo. The average age of patients in this study was 60 to 62 years, with 10%/16% diabetics and 48%/57% females, in the fish oil and placebo arms, respectively. After being followed for an average of 9 months for clinical and inflammatory endpoints, there was no difference observed between the fish oil and placebo arms in: (1) time to first of symptomatic AF occurrence lasting more than 30 seconds (64.1% vs 63.2%) (primary endpoint); (2) change in high-sensitivity C-reactive protein (hs-CRP) level (-11% for both); or (3) change in myeloperoxidase (MPO) level (-5% vs -9%). Despite the high dose, the fish oils were generally well tolerated without significant GI adverse effects leading to discontinuation (6 patients from the placebo and 5 from the fish oil groups).

Previous in vitro and some clinical studies have suggested that fish oils may exert an anti-inflammatory effect. However, this study showed that there was no differential effect on hs-CRP or MPO, and no clinical effect on AF recurrence. The prospective design and close attention to compliance with omega-3 index assessment are strengths of this study. There are some limitations as well: (1) the use of n-3 polyunsaturated fatty acid (PUFA) supplements, which contain both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a 2:1 ratio, may have blunted the beneficial effect of DHA compared with EPA; and (2) asymptomatic AF was not assessed with continuous Holter monitoring but instead with transtelephonic monitor.

Overall, the study provides compelling evidence that high-dose fish oils can be well tolerated but do not modulate the clinical recurrence of AF in low-risk patients with paroxysmal or persistent AF, at least when given in the short term. Whether fish oils have a role as a long-term therapy, following ablation therapy, as an adjunct to advanced antiarrhythmic therapy (ie, amiodarone), or following cardioversion for AF all remain to be explored in future studies.


Nigam A, Talajic M, Roy D, et al; AFFORD Investigators. Fish oil for the reduction of atrial fibrillation recurrence, inflammation, and oxidative stress.J Am Coll Cardiol. 2014;64:1441-1448. doi:10.1016/j.jacc.2014.07.956.

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