No association of omega-3 fatty acid supplements with CV risk reduction
Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks Meta-analysis of 10 Trials Involving 77917 IndividualsAung T, Halsey J, Kromhout D, et al. - JAMA Cardiol 2018; published online ahead of print
Data on the prevention of coronary heart disease (CHD) and major vascular events related to omega-3 fatty acids (FA) are conflicting [1-4]. Several guidelines indicated that it is debatable whether omega-3 FAs may exert a protective effect and more evidence is needed to justify their prescription [5,6]. In contrast, the American Heart Association recommended that the intake of omega-3 FAs for CHD prevention is likely justified in individuals with prior CHD and those with HFrEF . In this meta-analysis, the association between the consumption of omega-3 FA supplements and the risk of fatal CHD, non-fatal MI, stroke, major vascular events and all-cause mortality, and major vascular events in subgroups was evaluated.
Eligible for the meta-analysis were randomized clinical trials of marine-derived very-long-chain omega-3 FA supplements compared with placebo, or open-label control studies, with at least 500 participants and a scheduled duration of treatment of at least 1 year. Marine-derived omega-3 FAs include eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) found in fish and other seafood; no minimum daily dose of EPA or DHA was specified.
The pre-specified endpoints included non-fatal myocardial infarction (MI), death caused by CHD, stroke, coronary or non-coronary arterial revascularization events, major vascular events (a composite of the first occurrence of non-fatal MI or death caused by CHD, non-fatal or fatal stroke; or any revascularization procedure), and all-cause mortality.
The PRISMA guidelines  were followed for the conduct of meta-analysis of randomized trials. Pooled tabular data were obtained from 9 trials, and the detailed published results of 1 more study were used. The 10 studies together included 77,917 participants.
- During a mean follow-up of 4.4 years (1.0 – 6.2), omega-3FA supplementation (226-1800 mg/day EPA and 0-1700 mg/day) was not significantly associated with the RRs for: any CHD event (RR: 0.96; 95%CI: 0.90-1.01; P=0.12), CHD death (RR: 0.93; 99%CI: 0.83-1.03; P=0.05), non-fatal MI (RR: 0.97; 99%CI: 0.87-1.08; P=0.40), major vascular events (RR: 0.97; 95%CI: 0.93–1.01; P=0.10), stroke (RR: 1.03; 95%CI: 0.93-1.13; P=0.56), revascularization events (RR: 0.99; 95%CI: 0.94-1.04; P=0.61), all-cause mortality (RR: 0.96; 95%CI: 0.92-1.01; P=0.16)
- No significant heterogeneity was observed between the results of individual trials for non-fatal MI, CHD death, any CHD event, or all major vascular events.
- The results were similar after adjustment for multiple testing, and in pre-specified subgroups, including those defined by gender, history of CHD, history of diabetes, pretreatment levels of total cholesterol, high-density lipoprotein levels, low density lipoprotein levels, triglyceride levels, or prior use of statin therapy.
- There was some evidence of heterogeneity in the associations of omega-3 FAs with major vascular events by age (unadjusted P = 0.02) and by history of stroke (P = 0.06).
A large meta-analysis showed that omega-3 FA supplementation is not associated with a reduction in fatal and non-fatal CHD and other major vascular events. These data do not support the recommendation to use of ~1 g/d of omega-3-fatty acid supplements for the prevention of CV events. It will be interesting to see whether higher doses of omega-3 FAs (3-4 g/d) may have significant effects on risk of major vascular events.