Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators

Abstract

Aims: To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials.

Methods and results: We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79).

Conclusion: These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.

Figure 1

Forest plot of hazard ratios and overall estimate of the effect of fish oil of time to first confirmed tachyarrhythmia or death in the studies. Leaf et al. and Brouwer et al. lasted 1 year and Raitt et al. 2 years; data refer only to the first year of intervention. Shaded squares indicate the point estimates for each trial (hazard ratios), with the size of the square proportional to the contribution (inverse variance random effects weight) of the study to the overall estimate. Heterogeneity χ² P = 0.108. I² (variation in ES attributable to heterogeneity) = 55.1%. The overall pooled estimate and 95% CI are indicated by the dotted line and the clear diamond.

Figure 2

Forest plot of hazard ratios and overall estimate of the effect of fish oil on the first occurrence of tachyarrhythmia or death after inclusion in the studies until 1 year of intervention in the subgroups of patients with a history of coronary heart disease or ischaemic heart disease (A) and in a subgroup of patients with ventricular tachycardia at entry (B). Leaf et al. and Brouwer et al. lasted 1 year and Raitt et al. 2 years; data refer only to the first year of intervention. Shaded squares indicate the point estimates for each trial (hazard ratios adjusted for baseline characteristics), with the size of the square proportional to the contribution (inverse variance random effects weight) of the study to the overall estimate. The overall pooled estimate and 95% confidence interval are indicated by the dotted line and the clear diamond. (A) Subgroup of patients with coronary heart disease/ischaemic heart disease at entry. Heterogeneity χ² P = 0.295. I² (variation in ES attributable to heterogeneity) = 18.1%. (B) Subgroup of patients with ventricular tachycardia at entry. Heterogeneity χ² P = 0.003. I² (variation in ES attributable to heterogeneity) = 82.5%.

Figure 3

Time to first ventricular tachycardia (sustained ventricular tachycardia or ventricular fibrillation) for all patients in the pooled analysis (Raitt et al. and Brouwer et al.) (log-rank P = 0.79).

Figure 4

Hazard ratios of fish oil treatment for time to first ventricular tachyarrhythmia in the pooled analyses (Raitt et al. and Brouwer et al.) in the entire study population (primary analysis) and subgroups (subgroup analyses). Analyses are adjusted for age, gender, ejection fraction (squared because of skewness of the distribution), current smoking, New York Heart Association class for angina pectoris, New York Heart Association class for dyspnoea, valvular heart disease, prior myocardial infarction, cardiomyopathy, ventricular tachycardia as index arrhythmia, ventricular fibrillation as index arrhythmia, and use of anti-arrhythmic medication at baseline.