Omega-3 fatty acid supplements do not reduce CV risk

07/02/2018

A large meta-analysis showed that omega-3 fatty acid supplementation is not associated with a reduction in fatal and non-fatal CHD and other major vascular events.

Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks Meta-analysis of 10 Trials Involving 77917 Individuals
Literature - Aung T, Halsey J, Kromhout D, et al - JAMA Cardiol 2018; published online ahead of print

Background

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 [7]. 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 [8] 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.

Main results

  • 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 (unadj P=0.02) and by history of stroke (P=0.06).

Conclusion

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-FA supplements for the prevention of CV events. It will be interesting to see whether higher doses of omega-3 FA (3-4 g/d) may have significant effects on risk of major vascular events.

References

1. Tavazzi L, Maggioni AP, Marchioli R, et al; Gissi-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1223-1230.

2. Kromhout D, Giltay EJ, Geleijnse JM; Alpha Omega Trial Group. N-3 fatty acids and cardiovascular events aftermyocardial infarction. N Engl J Med. 2010;363(21):2015-2026.

3. Einvik G, Klemsdal TO, Sandvik L, et al. A randomized clinical trial on N-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk. Eur J Cardiovasc Prev Rehabil. 2010;17(5):588-592.

4. Bosch J, Gerstein HC, Dagenais GR, et al; ORIGIN Trial Investigators. N-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367(4):309-318.

5. Piepolo MF, Hoes AW, Agewal S, et al. 2016 guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-2381.

6. Catapano AL, Graham I, De Backer G, et al; Authors/Task Force Members; Additional Contributor. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016; 37(39):2999-3058.

7. Siscovick DS, Barringer TA, Fretts AM, et al. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease: a science advisory from the American Heart Association. Circulation. 2017;135 (15):e867-e884.

8. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100.

Find this article online at JAMA Cardiol 2018

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