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

Multicenter randomized trial in adults with implanted cardioverter-defibrillators at high risk for fatal ventricular arrhythmias. Eligible patients had prior cardiac arrest, sustained ventricular tachycardia, or syncope with inducible VT/VF; baseline characteristics were reported for about 200 fish oil participants and 202 placebo participants.

Participants received 4 1.0-g gelatin capsules daily of an ethyl ester concentrate of n-3 fatty acids from fish oil, providing a total EPA plus DHA dose of 2.6 g per day, for 12 months. The active capsules also contained tocopherol and butylated hydroxytoluene; the comparator was olive oil placebo.

Fish oil did not reach statistical significance for the primary end point of time to first ICD event or death, but it showed a favorable trend and signal in secondary and adherence-based analyses. At 12 months, events occurred in 28% of the fish oil group (n=57) versus 39% of the placebo group (n=78), with a relative risk of 0.72; when probable events were added, the relative risk was 0.69 (95% CL, 0.49 to 0.97; P=0.033), and multivariate adjustment gave an RR of 0.67 (95% CL, 0.49 to 0.97; P=0.024). On-treatment analysis for patients treated for at least 11 months favored fish oil as well (RR 0.62; 95% CL, 0.39 to 0.97; P=0.034; adjusted RR 0.52; P=0.0060). Total deaths were 25, with 13 in the fish oil group and 12 in placebo, and no serious adverse events were attributed to the oil supplements.

The primary endpoint narrowly missed conventional statistical significance (P=0.057), so the main claim rests partly on expanded-event and on-treatment analyses that are more vulnerable to bias. Follow-up was limited to 12 months, and the population was a selected, high-risk ICD cohort, which limits generalizability. Event counts were relatively modest, reducing precision for mortality and arrhythmia outcomes.