Abstract (as published in J Am Coll Cardiol)
Objective: The aim of this study was to evaluate the efficacy of polyunsaturated fatty acids (n-3 PUFA) for the prevention of recurrent atrial fibrillation (AF) in patients with normal sinus rhythm.
Background: Current pharmacological treatments to limit recurrent AF in patients with previous AF have limited efficacy and high rates of adverse events. Results of trials that tested the efficacy of n-3 PUFA provided heterogeneous results.
Methods: This was a prospective, randomized, double-blind, placebo-controlled, multicenter trial involving 586 outpatient participants with confirmed symptomatic paroxysmal AF that required cardioversion (n = 428), at least 2 episodes of AF in the 6 months before randomization (n = 55), or both (103). Patients were randomly allocated to n-3 PUFA (1 g/day) or placebo for 12 months. The primary endpoint was symptomatic recurrence of AF.
Results: There were no significant differences between patients allocated to placebo and those who received n-3 PUFA for the main outcome. At 12 months, 56 of 297 participants (18.9%) in the placebo group and 69 of 289 participants (24.0%) in the n-3 PUFA group had a recurrent symptomatic AF (hazard ratio: 1.28, 95% confidence interval: 0.90 to 1.83, p = 0.17). There was no difference between treatment with placebo and n-3 PUFA for any of the other pre-specified endpoints, including the composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding that occurred in 20 (6.7%) and 16 (5.5%) of patients randomized to placebo or n-3 PUFA, respectively (hazard ratio: 0.86, 95% confidence interval: 0.44 to 1.66, p = 0.65).
Authors’ Conclusion: Pharmacological supplementation with 1 g of n-3 PUFA for 1 year did not reduce recurrent AF.
O-3s & Secondary Prevention of Atrial Fibrillation
Macchia A Grancelli H Varini S Nul D Laffaye N Mariani J Ferrante D Badra R Figal J Ramos S Tognoni G and Doval HC on behalf of the GESICA Investigators (Epub ahead of print 2012 Dec 13). Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: Results of the FORWARD (randomized trial to assess efficacy of PUFA for the maintenance of sinus rhythm in persistent atrial fibrillation) trial. J Am Coll Cardiol. doi: 10.1016/j.jacc.2012.11.021.
Results from the current publication do not change the totality of the publicly available scientific evidence demonstrating a cardiovascular benefit of EPA and DHA in healthy populations, as well as in many populations with pre-existing cardiovascular ailments. Therefore, consumers should continue to eat fatty fish and take their omega-3 products for heart health.
What Else Should You Know?
The population of interest was diseased, not healthy.
Despite the current study being conducted like a drug trial, it was still a nutrition study and should have included some of the basics of a well-run nutrition study, including: precise composition of the n-3 PUFA supplement used, description of the subjects’ n-3 PUFA intake and status at both baseline and completion of the study, and description of the intake of other nutrients which may have interfered with the proposed action of interest. Studies, such as this one, attempt to be the ‘definitive study’ but without information on the nutrient(s) tested, it’s difficult to draw valid conclusions about the effects of supplemental intake.
The halting of the recruitment process mid-study resulted in an underpowered study, so this may not have been a failure to demonstrate an effect; rather a failure to detect an effect.
As in other studies failing to demonstrate an n-3 PUFA benefit, subjects in the current study were provided n-3 PUFAs in addition to receiving multiple drugs. This presents a significant challenge in trying to demonstrate a benefit of the n-3 PUFAs because patients are already taking drugs that contribute to achieving the same benefit as the n-3 PUFAs.
While the n-3 PUFA dose may have been similar to that used in the GISSI-Prevenzione trial (1, 2), baseline EPA/DHA plasma levels are very low in Argentina, so the dose may have been too low.
Global Organization for EPA and DHA Omega-3s (2013). Omega-3s & Secondary Prevention of Atrial Fibrillation [Peer commentary on the paper “Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: Results of the FORWARD (randomized trial to assess efficacy of PUFA for the maintenance of sinus rhythm in persistent atrial fibrillation) trial” by Macchia A Grancelli H Varini S Nul D Laffaye N Mariani J Ferrante D Badra R Figal J Ramos S Tognoni G and Doval HC on behalf of the GESICA Investigators (2013). J Am Coll Cardiol. doi: 10.1016/j.jacc.2012.11.021.].
1) GISSI-Prevenzione Investigators (1999). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 354:447-455.
2) Macchia A Varini S Grancelli H Nul D Laffaye N Ferrante D Tognoni G and Doval HC on behalf of the FORomegaARD investigators (2009). The rationale and design of the FORomegaARD Trial: A randomized, double-blind, placebo-controlled, independent study to test the efficacy of n-3 PUFA for the maintenance of normal sinus rhythm in patients with previous atrial fibrillation. Am Heart J 157:423-427.