A Randomized, Placebo‐Controlled Trial of Omega‐3 Fatty Acids for Inhibition of Supraventricular Arrhythmias After Cardiac Surgery: The FISH Trial

Abstract

BackgroundOmega-3 polyunsaturated fatty acids (n3-PUFAs) might have antiarrhythmic properties, but data conflict on whether n3-PUFAs reduce rates of atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG). We hypothesized that n3-PUFAs would reduce post-CABG AF, and we tested this hypothesis in a well-powered, randomized, double-blind, placebo-controlled, multicenter clinical trial.Methods and ResultsPatients undergoing CABG were randomized to pharmaceutical-grade n3-PUFAs 2 g orally twice daily (minimum of 6 g) or a matched placebo ≥24 hours before surgery. Gas chromatography was used to assess plasma fatty acid composition of samples collected on the day of screening, day of surgery, and postoperative day 4. Treatment continued either until the primary end point, clinically significant AF requiring treatment, occurred or for a maximum of 2 weeks after surgery. Two hundred sixty patients were enrolled and randomized. Before surgery, n3-PUFA dosing increased plasma n3-PUFA levels from 2.9% to 4% and reduced the n6:n3-PUFA ratio from 9.1 to 6.4 (both P<0.001). Similar changes were noted on postoperative day 4. There were no lipid changes in the placebo group. The rate of post-CABG AF was similar in both groups (30% n3-PUFAs versus 33% placebo, P=0.67). The post-CABG AF odds ratio for n3-PUFAs relative to placebo was 0.89 (95% confidence interval 0.52–1.53). There were no differences in any secondary end points.ConclusionsOral n3-PUFA supplementation begun 2 days before CABG did not reduce AF or other complications after surgery.Clinical Trial Registrationurl: http://www.clinicaltrials.gov Unique identifier: NCT00446966. (J Am Heart Assoc. 2012;1:e000547 doi: 10.1161/JAHA.111.000547.)

Do Fish Oil Omega-3 Fatty Acids Enhance Antioxidant Capacity and Mitochondrial Fatty Acid Oxidation in Human Atrial Myocardium via PPARγ Activation?

“…Although some small clinical trials showed early success in mitigating POAF with this therapy, the results of recent RCT's have been disappointing (6,8,9). These results may not be surprising, however, when viewed in the context of the large number of unanswered questions with regard to mechanism and appropriate treatment duration.…”

“…Specific focus was placed on assessing mitochondrial function and redox parameters, as these have been described to become altered in the heart with n-3 PUFA intake. Importantly, the therapeutic regimen used in this study is unique in that the dose of n-3 PUFAs is much higher, and the duration of therapy is longer, than in recent RCTs where n-3 PUFA therapy in the perioperative setting has been explored (6,8,9).…”

Omega-3 Fatty Acid Blood Levels

“…58,59 Recent investigations have reported no significant effect of 1 to 6 g/d fish oil several days before surgery, continuing postsurgery for 7 to 10 days, and achieving a mean EPA+DHA of 4.35%. 43,60,61 This suggests that supplementation around the time of heart surgery does not significantly reduce postoperative AF.…”

The effects of omega-3 polyunsaturated fatty acids on cardiac rhythm: A critical reassessment

“…Epidemiological data provide strong evidence for an inverse relationship between fatty fish consumption and cardiac mortality (Kromhout et al, 1985;Daviglus et al, 1997) while both experimental studies (McLennan et al, 1988;Billman et al, 1994) and clinical secondary preventions trials (Burr et al, 1989;Marchioli et al, 2002) have reported salutary actions of n−3 PUFAs against ventricular arrhythmias and sudden cardiac death. However, more recent studies in patients with heart disease (Burr et al, 2003;Raitt et al, 2005;Brouwer et al, 2006b;Yokoyama et al, 2007;GISSI-HF investigators, 2008;Kromhout et al, 2010;Rauch et al, 2010) or animals have yielded conflicting results, particularly with regards to the prevention of atrial fibrillation (Kowey et al, 2010;Mozaffarian et al, 2012;Sandesara et al, 2012). Thus, a scientific consensus on the effects of n−3 PUFA on cardiac rhythm has yet to be reached.…”