Perioperative supplementation with fish oil–derived fatty acids did not prevent postoperative atrial fibrillation in patients undergoing cardiac surgery, according to results from a large, randomized controlled trial.
Atrial fibrillation (AF) affects approximately one-third of patients who undergo cardiac surgery. Animal studies have suggested that the long-chain n-3-polyunsaturated fatty acids (PUFAs) found in fish oil have antiarrhythmic activity, and clinical trials have shown that habitual consumption of fish oil favorably affects physiological pathways that influence AF as well as overall cardiac mortality risk (J. Am. Coll. Cardiol. 2011;58:2047-67).
The new study, published online Nov. 5 in JAMA (doi:10.1001/jama.2012.28733) and presented simultaneously at the annual scientific sessions of the American Heart Association, demonstrated that fish oil supplementation beginning 2-5 days prior to cardiac surgery and continuing until hospital discharge did not reduce risk of postoperative atrial fibrillation.
For their research, Dr. Dariush Mozaffarian of the Harvard School of Public Health, Boston, and Dr. Roberto Marchioli of Consorzio Mario Negri Sud in Santa Maria Imbaro, Italy, and their colleagues randomized to fish oil capsules or placebo 1,516 patients who were scheduled for cardiac surgery at 28 centers in the United States, Italy, and Argentina.
Patients took 10 capsules, each 1-g capsule containing at least 840 mg of n-3-PUFAs, eicosapentaenoic acid (approximately 465 mg) plus docosahexaenoic acid (approximately 375 mg) as ethyl esters (Omacor) or matched placebo (olive oil) over 3-5 days before surgery, followed by two capsules per day until discharge or day 10 post surgery, whichever came first. The subjects’ average age was 64 years; 72% were men. Patients who took fish oil regularly were excluded from the study.
Centers were encouraged to use continuous electrocardiographic monitoring for at least 5 days post surgery. Twelve-lead ECGs were recommended daily and more frequently at the discretion of the treating physicians for symptoms or clinically suspected arrhythmia. Confirmatory rhythm strips or 12-lead ECGs were collected for all postoperative arrhythmias of at least 30 seconds’ duration.
AF episodes lasting 30 seconds or longer occurred after surgery in 233 (30.7%) controls and in 227 (30%) subjects given fish oil (odds ratio, 0.96 [95% confidence interval, 0.77-1.20]; P = .74). The two groups did not differ significantly in the number of AF episodes or the incidence of sustained AF episodes. Also, there was no significant difference in the risk of clinical bleeding, even though more than half of the study patients were also taking aspirin or other anticoagulants, the investigators reported.
Though the investigators hypothesized that they would see stronger efficacy of treatment among patients who consumed less than two servings a week of oily fish or those who had lower (<4%) plasma-PUFA levels at enrollment, no significant differences were found in those subgroups, they wrote.
Patients were identified and assigned to receive fish oil capsules for different durations (ranging from 2 to 5 days) prior to surgery, which could have resulted in the shorter durations being less effective, the investigators acknowledged. Subgroup analyses, however, did not detect significantly greater risk reduction associated with more days of fish oil before surgery.
The researchers noted that current best-practice guidelines for preventing postoperative AF were recommended to all participating surgical centers, "which could have reduced the influence of any additional therapy on risk of postoperative AF." Further, the supplement doses may have been too low to produce a benefit, even though phospholipid n-3-PUFA levels increased by an average of 40% by the time of surgery, "providing novel evidence that even short-term supplementation significantly influences circulating levels," they said.
Because of the known benefits of n-3-PUFAs on cardiovascular risk factors and physiologic pathways, "a more promising strategy may be long-term consumption to reduce the primary incidence of AF among ambulatory elderly adults with hypertension or other risk factors; such an approach should be tested in appropriately designed and powered clinical trials," the investigators wrote in their analysis.
The study was funded with grants from the National Institutes of Health, GlaxoSmithKline, Sigma Tau, and Pronova BioPharma, which also provided the capsules used in the study. None of the investigators declared conflicts of interest.