Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis - PubMed (original) (raw)

Abstract

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.

© 2021 The Author(s).

Conflict of interest statement

Dr. Deepak L. Bhatt reports grants from Amarin, grants from AstraZeneca, grants from Bristol-Myers Squibb, grants from Eisai, grants from Ethicon, grants from Medtronic, grants from Sanofi Aventis, grants from The Medicines Company, unfunded research collaborations with FlowCo, grants and other from PLx Pharma, unfunded research collaborations with Takeda, personal fees from Duke Clinical Research Institute, personal fees from Mayo Clinic, personal fees from Population Health Research Institute, personal fees, non-financial support and other from American College of Cardiology, personal fees from Belvoir Publications, personal fees from Slack Publications, personal fees from WebMD, personal fees from Elsevier. Dr Bhatt is on the edvisoty board of Medscape Cardiology and Regado Biosciences, and on the borad of directoprs of Boston VA Research Institute, reports personal fees and non-financial support from Society of Cardiovascular Patient Care, non-financial support from American Heart Association, personal fees from HMP Global, grants from Roche, personal fees from Harvard Clinical Research Institute (now Baim Institute for Clinical Research), other from Clinical Cardiology, personal fees from Journal of the American College of Cardiology, other from VA, grants from Pfizer, grants from Forest Laboratories/AstraZeneca, grants from Ischemix, other from St. Jude Medical (now Abbott), other from Biotronik, grants and other from Cardax, other from Boston Scientific, grants from Amgen, grants from Lilly, grants from Chiesi, grants from Ironwood, personal fees from Cleveland Clinic, personal fees from Mount Sinai School of Medicine, other from Merck, grants from Abbott, grants from Regeneron, other from Svelte, grants and other from PhaseBio, grants from Idorsia, grants from Synaptic, personal fees from TobeSoft, grants, personal fees and other from Boehringer Ingelheim, personal fees from Bayer, grants and other from Novo Nordisk, grants from Fractyl, personal fees from Medtelligence/ReachMD, personal fees from CSL Behring, grants and other from Cereno Scientific, grants from Afimmune, grants from Ferring Pharmaceuticals, other from CSI, grants from Lexicon, personal fees from MJH Life Sciences, personal fees from Level Ex, grants from Contego Medical, grants and other from CellProthera, personal fees from K2P, personal fees from Canadian Medical and Surgical Knowledge Translation Research Group, grants and other from MyoKardia/BMS, grants from Owkin, grants from HLS Therapeutics, grants and other from Janssen, grants from 89Bio, grants and other from Novo Nordisk, grants from Garmin, grants and collaborations from Novartis, outside the submitted work. Dr. Salim S. Virani reports grants from Department of Veterans Affairs, World Heart Federation, Tahir and Jooma Family, other from American College of Cardiology, outside the submitted work. Dr. Michael Miller reports personal fees from Amarin, outside the submitted work. Dr. Christie Ballantyne reports personal fees from Amarin, during the conduct of the study; grants and personal fees from Abbott Diagnostic, personal fees from AstraZeneca, grants and personal fees from Amgen, grants and personal fees from Esperion, personal fees from Matinas BioPharma, personal fees from Pfizer, grants and personal fees from Novartis, grants and personal fees from Regeneron, grants and personal fees from Roche Diagnostic, personal fees from Sanofi-Synthelabo, grants from National Institutes of Health, grants from American Heart Association, grants from American Diabetes Association, personal fees from Althera, personal fees from Novo Nordisk, grants from Akcea, personal fees from Denka Seiken, personal fees from Gilead, personal fees from Genentech, personal fees from Corvidia, personal fees from Arrowhead, personal fees from New Amsterdam, grants from Ionis, outside the submitted work. All the other authors have nothing to disclose.

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