Omega-3 Fatty Acids and Sudden Cardiac Death: An Updated Meta-Analysis of Randomized Trials

Abstract

Introduction: Observational studies suggested that marine omega-3 polyunsaturated fatty acids (PUFA) reduce sudden cardiac death (SCD). However, recent large trials have yielded conflicting results, necessitating a comprehensive update.
Methods: We performed a systematic review and meta-analysis of RCTs comparing omega-3 PUFA supplements (≥1 g/day) to placebo or usual care, with SCD as a prespecified outcome. Searched PubMed, Scopus, and Cochrane from inception to January 2024. Risk ratios (RR) calculated using random-effects.
Results: 14 RCTs (n=138,916) were included. Overall RR for SCD was 0.92 (95%CI 0.83–1.02; p=0.11). Heterogeneity moderate (I²=48%). In trials with high baseline omega-3 index (<4%), RR 0.79 (0.66–0.94); in those with higher baseline, RR 1.04 (0.92–1.18). No significant effect on total mortality (RR 0.97). Secondary prevention trials (post-MI) showed borderline benefit (RR 0.85, 0.72–1.00).
Discussion: The null overall finding contrasts with earlier meta-analyses. The benefit appears confined to populations with low habitual fish intake or low omega-3 status. Advances in background medical therapy (statins, revascularization) may have attenuated incremental benefit.
Conclusions: Omega-3 PUFA supplementation does not significantly reduce SCD in general populations but may benefit those with low baseline omega-3 status. Targeted rather than universal supplementation is recommended.