AFFORD: Fish Oil Does Not Prevent AF Recurrence in Low-Risk Patients

October 02, 2014

MONTREAL, QC — For low-risk patients with symptomatic paroxysmal or persistent atrial fibrillation who are not currently taking antiarrhythmic medication, a high-dose fish oil does not prevent the recurrence of AF, nor does it appear to reduce inflammation or oxidative stress[1].

The results, say researchers, "provide conclusive evidence that fish oil has no role in the rhythm-control management of patients with paroxysmal or persistent AF."

These are the primary results of the Multicenter Study to Evaluate the Effect of n-3 Fatty Acids on Arrhythmia Recurrence in Atrial Fibrillation (AFFORD), a Canadian study led by Dr Anil Nigam (Montreal Heart Institute, QC) published in the October 7, 2014 issue of the Journal of the American College of Cardiology.

To heartwire , Nigam said the patients studied represent the lowest-risk population in the secondary-prevention studies testing omega-3 fatty acids on the incidence of AF recurrence. They selected this group of patients because they believed the atrial substrate, which is involved in the initiation and maintenance of AF, wouldn't be as modified compared with individuals with longstanding AF. The hope was that these patients might benefit from treatment with omega-3 polyunsaturated fatty acids (PUFAs).

"All of the other studies took patients that were already on antiarrhythmics and who had a longer history of atrial fibrillation," he said. "Yet even in this low-risk population, our treatment didn't have an effect."

The AFFORD study

In total, 337 patients with symptomatic paroxysmal or persistent AF (mean duration 2.5 years since first AF diagnosis in the fish-oil arm) were randomized to 4 g of fish oil per day or to placebo. The 4-g dose included 1600 mg of eicosapentaenoic acid (EPA) and 800 mg of docosahexaenoic acid (DHA). The trial included a three-week loading phase to ensure the adequate incorporation of the omega-3 fatty acids into the tissue.

After an average follow-up of 271 days, the AF-recurrence rate was 64.1% in the fish-oil arm and 63.2% in the placebo arm, a difference that was not statistically significant. Regarding inflammation and oxidative stress, which was assessed by high-sensitivity C-reactive protein (CRP) and myeloperoxidase (MPO), respectively, there was no significant improvement with fish oil compared with placebo. The investigators point out, however, that CRP and MPO levels were within normal limits at baseline.

In an analysis looking at the omega-3 index, which measures EPA and DHA content in erythrocyte membranes as a percentage of total membrane fatty acids and which is used to assess adherence, the results showed there was a doubling of the omega-3 index in the fish-oil arm, from 4% to 8%. Nigam said levels this high had been shown previously to prevent ventricular arrhythmias. "In our case, it wasn't enough to prevent atrial arrhythmias," he said.

To heartwire , Nigam said there were two aspects to the study. The first was a clinical question: does fish oil prevent AF recurrence? The other question was a mechanistic one, which hadn't been addressed by previous investigations. Studies have suggested that inflammation and oxidative stress contribute to the initiation of AF and its recurrence. Yet in this study, CRP and MPO were not elevated at baseline and there was no benefit of omega-3 PUFAs on these markers. This suggests that inflammation and oxidative stress might not play a role in the low-risk AF patient with a short history of the arrhythmia, he said.

What About Preventing AF?

In an editorial[2], Dr Christine Albert (Brigham and Women's Hospital, Boston, MA) agrees with the conclusions of the AFFORD investigators, stating that omega-3 PUFA supplements "cannot be recommended on the basis of the available data as therapeutic agents to prevent recurrent or incident AF."

In summing up the evidence, Albert notes that smaller studies have shown omega-3 PUFAs reduced AF recurrence after cardioversion and cardiac surgery, but these results were not replicated in larger trials. Moreover, in a meta-analysis of diverse clinical trials with omega-3 fatty acids, the pooled risk estimates suggest no benefit on arrhythmia recurrence in patients with established AF or on postoperative AF. These trials had wide heterogeneity, though, with different patient populations, designs, n-3 PUFA dosages and formations, and small sample sizes.

"Given the potential pleiotropic actions of n-3 PUFAs, it is quite plausible that these agents might be more effective at preventing, rather than reversing, the development of the atrial substrate associated with AF and/or that longer-term therapy may be required to have a significant impact on atrial remodeling in patients with established AF," suggested Albert.

There is currently a large-scale primary-prevention study of nearly 26 000 men and women in the US treated with vitamin D3 and/or 1 g of omega-3 fatty acids. The goal of the five-year Vitamin D and Omega-3 (VITAL) trial is to determine whether the supplements reduce the risk of cancer, heart disease, and stroke in healthy individuals. It is led by Drs JoAnn Manson and Julie Buring (Brigham and Women's Hospital), and the full results are expected in 2017.

The authors report no conflicts of interest.

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