SOFA: Study of omega-3 fatty acids and ventricular arrhythmia. A multicenter, randomized clinical trial.

Background Very long-chain n-3 polyunsaturated fatty acids (n-3 PUFA, also named omega-3 fatty acids) from fish may reduce risk of sudden death through reducing the susceptibility for cardiac arrhythmia. However, current evidence is not conclusive. Objective The Study on Omega-3 Fatty acids and ventricular Arrhythmia (SOFA) investigated the effect of n-3 fatty acids from fish on the incidence of recurrent ventricular arrhythmia and all-cause mortality in patients with an implantable cardioverter defibrillator (ICD). Methods SOFA is a parallel, placebo-controlled, double blind trial performed in 26 clinical centres across Europe. We randomized 546 patients with an ICD to treatment with either 2 g/d of fish oil (n= 273) or placebo (n=273), and followed them for a period of 234 +/- 125 days (mean +/- SD). Patients were eligible if they had experienced spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) within one year before enrolment. Patients were excluded if they had used supplemental n-3 fatty acids during the past three months, or if they consumed more than 267 mg/day of n-3 fatty acids from fish or seafood. The primary endpoint was spontaneous ventricular tachyarrhythmia episodes as recorded by the ICD, or all-cause mortality. Results 70% of patients in the fish oil group versus 67% in the placebo group survived free from VT or VF (p=0.24, log-rank test, intention to treat analysis). The hazard ratio for occurrence of at least one event was 0.84 (95% CI: 0.62-1.13) for patients receiving fish oil. The hazard ratio for compliant patients was 0.73 (0.51-1.06; n=399, per protocol analysis). In subgroup (intention to treat) analyses the hazard ratio was 0.76 (0.51-1.11) for 302 patients with a VT (and no other index arrhythmias) at entrance and 0.72 (0.49-1.05) for patients with prior myocardial infarction (MI; n=342). Conclusion SOFA does not indicate a strong protective effect of intake of n-3 fatty acids from fish oil on life-threatening ventricular arrhythmia in ICD patients. In patients who previously experienced an MI there was a non-significant trend towards a beneficial effect