Prevention of Fatal Arrhythmias in High-Risk Subjects by Fish Oil n-3 Fatty Acid Intake

Abstract

Background— The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a randomized trial of post–myocardial infarction patients. Therefore, we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients. Methods and Results— Four hundred two patients with implanted cardioverter/defibrillators (ICDs) were randomly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months. The primary end point, time to first ICD event for ventricular tachycardia or fibrillation (VT or VF) confirmed by stored electrograms or death from any cause, was analyzed by intention to treat. Secondary analyses were performed for “probable” ventricular arrhythmias, “on-treatment” analyses for all subjects who had taken any of their oil supplements, and “on-treatment” analyses only of those subjects who were on treatment for at least 11 months. Compliance with double-blind treatment was similar in the 2 groups; however, the noncompliance rate was high (35% of all enrollees). In the primary analysis, assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause (risk reduction of 28%; P =0.057). When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P =0.033. For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P =0.034). Conclusions— Although significance was not achieved for the primary end point, this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias, regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias.

n-3 fatty acids and cardiovascular disease

“…Surprisingly, in the study by Raitt et al 23 recurrent episodes of ventricular tachycardia or fibrillation occurred more frequently in patients on n-3 PUFA, and the time to event was reduced. In contrast to these findings, Leaf et al 20 observed a trend towards an increase in time to recurrent ventricular tachycardia or fibrillation or death in the n-3 PUFA group in the Fatty Acid Arrhythmia Trial (FAAT) in which 402 patients with an ICD were randomized to either 2.6 g/day n-3 PUFA or olive oil for 1 year. Moreover, Brouwer and coworkers 24 found no strong evidence of a protective effect of omega-3 PUFA given at a daily dose of 0.9 g for 1 year as compared to that of sunflower oil, against ventricular arrhythmias in 546 patients with ICD, although a trend towards decreased ventricular arrhythmias or death was noted in the subgroup of patients with a prior myocardial infarction.…”

“…Experimental work in animal models have shown that n-3 PUFA alter the electrophysiological properties of the heart, 20 and it has been suggested that stabilization of cell membranes might explain the anti-arrhythmic and anti-fibrillatory effects of n-3 PUFA. 21 The early effect of n-3 PUFA on total mortality and sudden death, as demonstrated by the time-course analysis of the results of the GISSI-Prevenzione study, supported a hypothesis of an anti-arrhythmic potential of n-3 PUFA.…”

“…21 The early effect of n-3 PUFA on total mortality and sudden death, as demonstrated by the time-course analysis of the results of the GISSI-Prevenzione study, supported a hypothesis of an anti-arrhythmic potential of n-3 PUFA. 22 Recently, three randomized clinical trials 20,23,24 have been performed in patients with an implantable cardioverter defibrillator (ICD), to evaluate the antiarrhythmic effects of n-3 PUFA. In the study by Raitt et al 23 no significant decrease in total mortality was observed among 200 patients with an ICD and a recent episode of sustained ventricular tachycardia or ventricular fibrillation receiving EPA/DHA 1.3g/day as compared to olive oil for 2 years.…”

n-3 Fatty acids and cardiovascular disease: Actions and molecular mechanisms

“…The biological effects of n-3 FA on atherosclerosis include preventing arrhythmias [8,12,[19][20][21][22][23][24], decreasing platelet aggregation [27][28][29], lowering plasma triglycerides [30][31][32][33][34][35], increasing HDL cholesterol and LDL particle size [36][37][38][39][40], decreasing blood pressure [42][43][44][45], reversing cholesterol accumulation from atheromatous plaques [46,47] and decreasing inflammation [48][49][50].…”

“…In the GISSI trial, Macchia et al [19] found that the effect of n-3 FA on sudden death reduction was greater in patients with left ventricular systolic dysfunction, suggesting that one primary effect of n-3 FA therapy in patients with prior myocardial infarction is antiarrhythmogenic. Subsequent studies have suggested that the major impact of n-3 FA on arrhythmias is in patients with prior MI [12,20,21]. Chrysohoou et al [22] in a sample of Greek adults found that patients who consumed 300 g fish/week or more had a 29.2% lower likelihood of having QTc intervals >0.45 s (P=0.03), therefore n-3 FA could provide antiarrhythmic protection at a population level.…”