Published: Sep 30, 2014
By Salynn Boyles, Contributing Writer, MedPage Today
Action Points
High-dose fish oil did not reduce atrial fibrillation recurrence compared to placebo in patients with a history of atrial fibrillation who were not receiving conventional antiarrhythmic therapy.
Additionally, fish oil did not reduce markers of inflammation or oxidative stress in this population.
High-dose fish oil failed to reduce atrial fibrillation (Afib) recurrence in patients with a history of Afib who were not receiving conventional antiarrhythmic therapy, Canadian researchers said.
The AFFORD trial’s primary endpoint was the time to first symptomatic or asymptomatic Afib recurrence lasting greater than 30 seconds, and among patients who took 4 g daily of fish oil, the primary endpoint occurred in 64.1%, versus 63.2% of patients in the placebo arm, for a hazard ratio of 1.10 (95% CI 0.84-1.45, P=0.48), reported Anil Nigam, MD, of the Montreal Heart Institute Research Center, and colleagues.
In addition, high-dose fish oil did not reduce inflammation or oxidative stress markers in the study population, which could explain its lack of efficacy, they wrote online in the Journal of the American College of Cardiology.
“The lack of a beneficial effect of fish oil on [Afib] recurrence in the AFFORD may be at least partially due to its lack of effect on these pathophysiological processes, which have been implicated in [Afib] development and progression,” they explained. “We believe that our results provide conclusive evidence that fish oil has no role in the rhythm-control management of patients with paroxysmal or persistent Afib.”
Fish Oil and Afib: The Backstory
Known as AFFORD, the study is one of several recent clinical trials — including a 2012 study presented at a meeting of the American Heart Association — that found no benefit for omega-3 fatty acids from fish oil for the prevention of Afib recurrence.
In the FORWARD trial of 586 patients at high risk for Afib recurrence, a year of daily fish oil supplements (1 g daily for 850-882 mg of ethyl esters) did not prolong time to recurrence or improve other outcomes in patients with prior paroxysmal Afib or recent cardioconversion for persistent Afib.
And in a 2010 study, high-dose (4-8 g per day) omega-3 supplements over 24 weeks failed to demonstrate an advantage over placebo for preventing Afib recurrences.
“To date, randomized trials of fish oil for the prevention of atrial fibrillation recurrence have provide mixed, generally negative results,” the researchers wrote, adding that AFFORD was comparable to the two largest studies (FORWARD and the 2010 trial with respect to sample size and methodology).
A major strength of the current study was the dosing size, they pointed out, as the 4 g per day dose is generally considered the highest dose of fish oil that is free from gastrointestinal side effects.
“A higher dose would have made blinding not feasible in the context of a randomized, placebo-controlled trial … we chose this dose because of our [unpublished] pilot data, showing potentially greater efficacy for the prevention of [Afib] recurrence relative to the standard 1-g/day dose recommended for the secondary prevention of coronary heart disease,” they explained.
Study Details
AFFORD enrolled 337 patients from 2009 to 2012 who had experienced symptomatic paroxysmal or persistent Afib within 6 months of enrollment. Patients were excluded if they had used n-3 PUFA supplements within 3 months of enrollment. They were randomized to fish oil or placebo and followed for an average of 271 days, up to 16 months.
Recurrence of afib was monitored by weekly transtelephonic monitoring transmissions to detect potentially asymptomatic episodes, while symptomatic episodes were assessed by transtelephonic monitor strips, 12-lead electrocardiography, or any implanted device.
The primary endpoint for the study was time to first asymptomatic or symptomatic afib recurrence lasting ≥30 seconds. Secondary endpoints included inflammation and oxidative stress, measured by high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (MPO) at baseline and 6-month follow up.
A total of 297 (88%) patients completed the study, and dropouts were distributed evenly among the fish-oil treatment and placebo groups.
In addition to similar rates of Afib recurrence, the two groups experienced similar levels of inflammation and oxidative stress. hc-CRP was not elevated at baseline (mean value of about 2 mg/dl), and decreased modestly in both groups. Similarly, MPO was within normal limits at baseline and decreased slightly in both groups.
Omega-3 Index, Afib Recurrence
While previous studies showed an inverse relationship between n-3 fatty acid blood content and risk of de novo Afib, the study is among the first to prospectively address the relationship between the omega-3 index and Afib recurrence, the researchers wrote.
They reported a doubling of the omega-3 index in patients in the fish oil group (about 8%) versus no change in the placebo group. They explained that, previously, an omega-3 index of about 8% was “noted to be associated with optimal cardioprotection and a 90% reduction in the risk of sudden cardiac death. Although we achieved this level in the AFFORD, fish oil did not provide protection against recurrent atrial arrhythmias.”
Potential study limitations included the formulation of n-3 PUFA supplements used, which contained eicosapentaenoic acid (EPA) and (docosahexaenoic acid) DHA in a 2:1 ratio, and the fact that study participants were not fitted with implantable loop recorders, which are costly but provide optimal detection of Afib recurrence. The researchers also did not control for dietary sources of omega-3 fatty acid.
And while they did observe a trend toward a higher risk of cardiovascular death and hospitalization in the fish oil supplement group, they considered this association spurious due to the small numbers and multiple testing.
The study was funded by the Canadian Institutes for Health Research and the Heart and Stroke Foundation of Quebec.
Genuine Health provided the study medication and placebo capsules.
Nigam and co-authors declared no relevant relationships with industry.
From the American Heart Association: