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

Khan SU, Lone AN, Khan MS, Virani SS, Blumenthal RS, Nasir K, Miller M, Michos ED, Ballantyne CM, Boden WE, Bhatt DL. Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis. EClinicalMedicine. 2021 Aug 1; 38:100997.

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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,, 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];   =  0.01), non-fatal myocardial infarction (MI) (RR, 0.87 [0.81-0.93];   =  0.0001), coronary heart disease events (CHD) (RR, 0.91 [0.87-0.96];   =  0.0002), major adverse cardiovascular events (MACE) (RR, 0.95 [0.92-0.98];   =  0.002), and revascularization (RR, 0.91 [0.87-0.95];   =  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.

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