A double-blind, placebo-controlled, multinational randomized trial of more than 1,500 cardiac surgery patients revealed that ingestion of fish oil prior to and after surgery had no impact on the rate of post-surgical atrial fibrillation (AF). Findings from OPERA were presented Nov.5 at the American Heart Association meeting in Los Angeles and and simultaneously published in the Journal of the American Medical Association.
The OPERA (Omega-3 Fatty Acids for the Prevention of Post-Operative Atrial Fibrillation) trial enrolled 1,516 patients over the age of 18 who were scheduled for cardiac surgery on the following day or later who demonstrated the presence of sinus rhythm on screening electrocardiogram (ECG). Patients were enrolled from 28 centers in the U.S., Italy and Argentina. The study took place between August 2010 and June 2012.
Dariush Mozaffarian, MD, of the Harvard School of Public Health in Boston, and colleagues block randomized patients to receive either 1 gram capsules containing 840mg of eicosapentaenoic acid plus docosahexaenoic acid (Omacor, ProNova BioPharma), or a matched placebo of olive oil. Patients and treating physicians were all blind as to treatment assignment.
The mean of age of the patients in the fish oil group was slightly higher (63.8 years vs. 63.6 years) and 72.7 percent of the patients in the fish oil group were men vs. 71.6 percent of the patients in the placebo group. The groups were well-matched according to all other relevant criteria.
All patients received preoperative loading doses of 10 capsules over several days and two capsules per day until hospital discharge or postoperative day 10, whichever came first.
Hospitals administered ECG at least daily or more often at the discretion of the treating physician. The primary endpoint was postoperative AF of at least 30 seconds duration documented by rhythm strip or 12-lead ECG. Secondary endpoints were postoperative AF that was sustained, symptomatic or treated with pharmacological or electronic cardioversion; postoperative AF excluding atrial flutter, time to first postoperative AF and number of postoperative hospital episodes per patient.
The results of the trial showed little difference between the groups. In the placebo group, 30.7 percent of patients reached the primary endpoint compared to 30 percent in the fish oil group. There were no significant variations in the rates of secondary postoperative AF endpoints between patients in the two groups. The researchers did find an association between lowered risk of postoperative AF among patients undergoing surgery on the aortic or mitral valves.
The patients receiving fish oil received significantly fewer packed red blood cell transfusions. Otherwise, there was no difference in bleeding events between the two groups, a result the researchers claimed confirmed findings in smaller trials that fish oil did not increase bleeding risk.
"Our findings provide no evidence that short-term [fish oil] supplementation provides clinically relevant anti-arrhythmic effects in the acute setting of cardiac surgery," Mozaffarian et al wrote. "The effects of cardiac surgery on neurohormonal, oxidative and inflammatory activation and atrial remodeling may simply be too great to be countered by most drugs."
The researchers went on to comment that postsurgical AF remains an intractable problem, and urged more investigation of the "physiological, structural and molecular underpinnings of postoperative AF to allow novel targeted preventive and therapeutic interventions."
Noting that other studies have demonstrated that fish oil favorably influences blood pressure, systemic vascular resistance, heart rate and many other factors related to cardiac health, the authors opined that the outcome of OPERA and other recent studies "point toward a reduction in cardiac death as the principal cardiovascular benefit of long-term" use of fish oil.