Neither idea is likely after VITAL and VITAL-Rhythm, said Dr. Schnabel, who spoke as an invited discussant after Albert’s formal presentation at AHA 2020.
That omega-3 fatty acid supplements may not improve AF incidence or risks has also been evident from many clinical trials and observational studies. Several, including REDUCE-IT, included some evidence for increasing risk for AF with marine-oil supplement intake. That may have happened in VITAL-Rhythm as well.
“While there was no evidence that the omega-3 three fatty acids prevented atrial fibrillation, there was a signal of perhaps more atrial fibrillation in the omega-3 fatty-acids group,” said Dr. Piccini, who directs his center’s electrophysiology clinical trials program.
A sensitivity analysis limited to participants who adhered to their assigned regimens, as opposed to the main intention-to-treat (ITT) analysis, showed a nonsignificant 13% increased hazard ratio for incident AF for the marine-oil supplement group. It reached a P value of .09, which can be interpreted as a trend.
“There are a few studies that have now showed a trend or an increased incidence of arrhythmia in patients treated with omega-3 fatty acids,” Dr. Piccini noted. “I don’t think it’s definitive, but it’s certainly something to keep an eye on.”
VITAL-Rhythm included an electrocardiography (ECG) substudy, yet to be reported, that should yield more insights about any such effects of marine-oil or vitamin D supplements in the trial, Dr. Albert said at the briefing.
The ancillary study assigned its 25,119 patients (mean age, 67 years; 51% women) to take vitamin D3 at 2000 IU/day, marine-oil supplements containing omega-3 fatty acids at 840 mg per day – 460 mg eicosapentaenoic acid (EPA) plus 380 mg docosahexaenoic acid (DHA) (Omacor, Pronova BioPharma) – or their placebos in a 2 x 2 randomization.
Incident cases of AF were identified through annual questionnaires in which the participants self-reported whether they had received a physician diagnosis of the arrhythmia, supplemented by Centers for Medicare & Medicaid Services claims data for AF hospital and clinical visits. Those led to a review of inpatient and outpatient records, from which AF events were adjudicated by an endpoint committee.
An electrocardiogram (72.9%) or physician’s report (27.1%) confirmed the AF diagnosis as the protocol required.
By those standards, 900 incident cases were identified, for a rate of 3.6% over a median of 5.3 years. They were paroxysmal in 58.4%, persistent in 38.4%, and indeterminant in 3.1%, Dr. Albert reported.
Of the 12,542 patients assigned to marine-oil caps by ITT, 469 (3.74%) developed incident AF in the ITT analysis, compared to 431 of 12,577 (3.43%) who received placebo, for an adjusted hazard ratio (HR) of 1.09 (95% CI, 0.96-1.24; P = .19).
The results were similar in two sensitivity analyses, one of which omitted patients with AF who may have had symptoms before randomization and another excluding those whose incident AF was identified solely in CMS data. But in the third “on treatment” sensitivity analysis, the HR for events was 1.13 (95% CI, 0.98-1.30; P = .09).
Outcomes for the vitamin D randomization were nearly the same, for an HR of 1.09 (95% CI, 0.96-1.25; P = .19) by ITT; the results were similar in all three sensitivity analyses.