Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis

EClinicalMedicine. 2021 Jul 8:38:100997. doi: 10.1016/j.eclinm.2021.100997. eCollection 2021 Aug.


Background: The effects of omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on cardiovascular outcomes are uncertain. We aimed to determine the effectiveness of omega-3 FAs on fatal and non-fatal cardiovascular outcomes and examine the potential variability in EPA vs. EPA+DHA treatment effects.

Methods: We searched EMBASE, PubMed, ClinicalTrials.gov, and Cochrane library databases through June 7, 2021. We performed a meta-analysis of 38 randomized controlled trials of omega-3 FAs, stratified by EPA monotherapy and EPA+DHA therapy. We estimated random-effects rate ratios (RRs) with (95% confidence intervals) and rated the certainty of evidence using GRADE. The key outcomes of interest were cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation (AF). The protocol was registered in PROSPERO (CRD42021227580).

Findings: In 149,051 participants, omega-3 FA was associated with reducing cardiovascular mortality (RR, 0.93 [0.88-0.98]; p = 0.01), non-fatal myocardial infarction (MI) (RR, 0.87 [0.81-0.93]; p = 0.0001), coronary heart disease events (CHD) (RR, 0.91 [0.87-0.96]; p = 0.0002), major adverse cardiovascular events (MACE) (RR, 0.95 [0.92-0.98]; p = 0.002), and revascularization (RR, 0.91 [0.87-0.95]; p = 0.0001). The meta-analysis showed higher RR reductions with EPA monotherapy (0.82 [0.68-0.99]) than with EPA + DHA (0.94 [0.89-0.99]) for cardiovascular mortality, non-fatal MI (EPA: 0.72 [0.62-0.84]; EPA+DHA: 0.92 [0.85-1.00]), CHD events (EPA: 0.73 [0.62-0.85]; EPA+DHA: 0.94 [0.89-0.99]), as well for MACE and revascularization. Omega-3 FA increased incident AF (RR, 1.26 [1.08-1.48]). EPA monotherapy vs. control was associated with a higher risk of total bleeding (RR: 1.49 [1.20-1.84]) and AF (RR, 1.35 [1.10-1.66]).

Interpretation: Omega-3 FAs reduced cardiovascular mortality and improved cardiovascular outcomes. The cardiovascular risk reduction was more prominent with EPA monotherapy than with EPA+DHA.

Funding: None.

Keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Meta-analysis; Omega-3 fatty acid.