CHICAGO – High-dose, prescription omega-3 fatty acids did no better than placebo in preventing the recurrence of symptomatic paroxysmal atrial fibrillation episodes in the P-OM3 trial.
At 24 weeks, the primary end point of symptomatic recurrence of atrial fibrillation (AF) or flutter in patients with paroxysmal AF occurred in 52% of those receiving prescription omega-3 and 48% of those given placebo, a nonsignificant difference.
Those results were consistent across all prespecified subgroups, including age; gender; smoking status; and use of ACE inhibitors, angiotensin II receptor blockers, or statins, Dr. Peter R. Kowey reported at the annual scientific sessions of the American Heart Association.
In addition, the median annualized numbers of AF/flutter rescue episodes were similar: 2.17 in the placebo group vs. 2.24 in the prescription omega-3 group.
Patients with symptomatic paroxysmal AF made up the majority (82%) of the 663-patient trial, as this group was thought most likely to respond to omega-3 polyunsaturated fatty acids. All patients were without substantial structural heart disease and in normal sinus rhythm at baseline without the use of antiarrhythmic drugs.
Secondary analyses showed no statistically significant differences in the rates of symptomatic AF or flutter among patients with persistent AF treated with prescription omega-3 (50%) or placebo (33%), and between treatment groups when both the paroxysmal and persistent AF patients were combined (52% vs. 46%, respectively), he said.
Although previous trials have produced mixed results regarding the efficacy of omega-3 fatty acids in atrial fibrillation, the current trial "demonstrated incontrovertibly" that patients with paroxysmal AF who received this drug did no better than those who received placebo, Dr. Kowey, chief of cardiovascular disease with Main Line Health, Lankenau Hospital in Wynnewood, Pa., said during a press briefing.
Invited discussant Dr. Christine Albert of Brigham and Women’s Hospital in Boston said that the current data are sorely needed because of the large number of patients taking omega-3 fatty acids, but that patients should wait before abandoning the popular drug. She pointed out that observational studies of fish intake and AF have shown a benefit in elderly patients as well as a potentially negative effect in younger patients, suggesting that omega-3 fatty acids may have different effects in different patient populations.
This raises the question of whether subtypes of AF may still benefit from omega-3, including post-operative AF, older patients with chronic heart failure or structural heart disease, and those with persistent or chronic AF, Dr. Albert said.
The phase III OPERA trial is currently testing whether peri-operative omega-3 fatty acids will decrease the occurrence of post-op AF, compared with placebo, in patients undergoing cardiac surgery. She also noted that P-OM3 did not address the longer-term effects of omega-3, whether lower doses could be more effective, and whether omega-3 fatty acids could be useful in the primary prevention of AF.
"The take-home point is that right now we really don’t have any evidence that these omega-3 fatty acids prevent symptomatic atrial fibrillation in paroxysmal patients," Dr. Albert said. "I do think there is a role for further large-scale randomized trials, which are ongoing."
As expected, prescription-grade omega-3 was extremely well tolerated in P-OM3, with a very low incidence of any adverse event and no difference in rates of serious adverse events, Dr. Kowey said. In all, 5% of the placebo group and 4% of the omega-3 group discontinued therapy because of an adverse event.
The trial randomized 542 patients with symptomatic paroxysmal AF and 121 patients with persistent AF to 8 g/day of prescription omega-3 for 7 days and 4 g/day thereafter or placebo. Of these, 527 paroxysmal patients and 118 persistent AF patients were evaluable, with the remainder lost to follow-up, excluded for lack of ECG monitoring data, or withdrawing.
GlaxoSmithKline funded the P-OM3 trial. Dr. Kowey has served as a consultant for Reliant Pharmaceuticals and GSK. Dr. Albert disclosed consulting fees and honoraria from Novartis and research grants from Siemens and St. Jude Medical.