Abstract
BackgroundThe 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.MethodsWe 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).FindingsIn 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]).InterpretationOmega-3 FAs reduced cardiovascular mortality and improved cardiovascular outcomes. The cardiovascular risk reduction was more prominent with EPA monotherapy than with EPA+DHA.FundingNone.
Highlights
Omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, may reduce the risk of atheroscleroticResearch in contextEvidence before this studyEicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differ in their biological effects on membrane structure and lipid metabolism
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 [0.81À0.93]; p = 0.0001), coronary heart disease events (CHD) (RR, 0.91 [0.87À0.96]; p = 0.0002), major adverse cardiovascular events (MACE) (RR, 0.95 [0.92À0.98]; p = 0.002), and revascularization (RR, 0.91 [0.87À0.95]; p = 0.0001)
The leave-one-out meta-analysis Appendix p 10 and 11), or sensitivity analyses using fixed-effects model, or exclusion of older trials, trials with a high risk of bias, or trials with low cardiovascular disease risk did not influence the results (Appendix p 12). In this meta-analysis of 38 trials comprising 149,051 adult participants, we noted that omega-3 FA was associated with reducing cardiovascular mortality and other cardiovascular outcomes
Summary
Omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, may reduce the risk of atheroscleroticResearch in contextEvidence before this studyEicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differ in their biological effects on membrane structure and lipid metabolism. Omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, may reduce the risk of atherosclerotic. In this updated meta-analysis of 38 randomized controlled trials, omega-3 FAs were associated with reducing cardiovascular mortality and other cardiovascular outcomes. A meta-analysis of EPA trials showed greater relative risk reductions in cardiovascular outcomes than those of EPA+DHA. The effects of omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on cardiovascular outcomes are uncertain. The meta-analysis showed higher RR reductions with EPA monotherapy (0.82 [0.68À0.99]) than with EPA + DHA (0.94 [0.89À0.99]) for cardiovascular mortality, non-fatal MI (EPA: 0.72 [0.62À0.84]; EPA+DHA: 0.92 [0.85À1.00]), CHD events (EPA: 0.73 [0.62À0.85]; EPA+DHA: 0.94 [0.89À0.99]), as well for MACE and revascularization.
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