Anticoagulation Strategies in Atrial Fibrillation: A Systematic Review and Evidence Synthesis of Direct Oral Anticoagulants Versus Warfarin for Stroke Prevention in Non-Valvular Atrial Fibrillation

Anticoagulation Strategies in Atrial Fibrillation: A Systematic Review and Evidence Synthesis of Direct Oral Anticoagulants Versus Warfarin for Stroke Prevention in Non-Valvular Atrial Fibrillation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Anticoagulation Strategies in Atrial Fibrillation: A Systematic Review and Evidence Synthesis of Direct Oral Anticoagulants Versus Warfarin for Stroke Prevention in Non-Valvular Atrial Fibrillation Safana Abdullah Algutaini, Ebaa Alghazi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8497769/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Atrial fibrillation (AF) affects over 33 million individuals globally and confers a five-fold increased risk of ischemic stroke. While warfarin has been the traditional anticoagulant, direct oral anticoagulants (DOACs) have emerged as potential alternatives. This systematic review synthesizes evidence comparing the efficacy and safety of DOACs versus warfarin in non-valvular AF. Objectives To compare the efficacy, safety, and risk-benefit profiles of DOACs versus warfarin; evaluate comparative effectiveness among individual DOACs; assess risk stratification tools; and review anticoagulation management in special populations. Methods A comprehensive systematic literature search was conducted across PubMed, EMBASE, Cochrane CENTRAL, and Web of Science databases (inception through December 2025). We included randomized controlled trials (RCTs), published meta-analyses, systematic reviews, and large cohort studies (n > 1000) comparing anticoagulation strategies in adults with non-valvular AF. Two independent reviewers screened studies and extracted data. Quality was assessed using Cochrane Risk of Bias tool (RCTs) and Newcastle-Ottawa Scale (observational studies). Results Of 1,245 identified records, 55 studies met inclusion criteria (15 RCTs, 12 meta-analyses, 8 systematic reviews, 20 cohort studies), with 71,683 patients derived from the four pivotal randomized trials. Standard-dose DOACs reduced stroke/systemic embolism risk by 19% compared to warfarin (HR 0.81, 95% CI 0.74–0.89) and intracranial hemorrhage by 55% (HR 0.45, 95% CI 0.37–0.56). All-cause mortality was reduced by 8% (HR 0.92, 95% CI 0.87–0.97). Among DOACs, apixaban demonstrated the lowest gastrointestinal bleeding risk (HR 0.72–0.81 vs. other agents). Risk stratification using CHA₂DS₂-VASc and HAS-BLED scores remains essential for individualized decision-making. Conclusions DOACs are superior to warfarin for stroke prevention in most patients with non-valvular AF, with a particularly favorable safety profile regarding intracranial hemorrhage. Individual DOAC selection should be tailored to patient characteristics, comorbidities, and bleeding risk. Special populations require individualized approaches, with careful consideration of renal function, drug interactions, and patient preferences. Atrial fibrillation anticoagulation direct oral anticoagulants warfarin stroke prevention systematic review evidence synthesis PRISMA Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8497769","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":568194064,"identity":"eae05be8-fd68-43f1-b93a-6dae7187b336","order_by":0,"name":"Safana Abdullah 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Prevention in Non-Valvular Atrial Fibrillation\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Atrial fibrillation, anticoagulation, direct oral anticoagulants, warfarin, stroke prevention, systematic review, evidence synthesis, PRISMA","lastPublishedDoi":"10.21203/rs.3.rs-8497769/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8497769/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAtrial fibrillation (AF) affects over 33\u0026nbsp;million individuals globally and confers a five-fold increased risk of ischemic stroke. While warfarin has been the traditional anticoagulant, direct oral anticoagulants (DOACs) have emerged as potential alternatives. This systematic review synthesizes evidence comparing the efficacy and safety of DOACs versus warfarin in non-valvular AF.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo compare the efficacy, safety, and risk-benefit profiles of DOACs versus warfarin; evaluate comparative effectiveness among individual DOACs; assess risk stratification tools; and review anticoagulation management in special populations.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA comprehensive systematic literature search was conducted across PubMed, EMBASE, Cochrane CENTRAL, and Web of Science databases (inception through December 2025). We included randomized controlled trials (RCTs), published meta-analyses, systematic reviews, and large cohort studies (n\u0026thinsp;\u0026gt;\u0026thinsp;1000) comparing anticoagulation strategies in adults with non-valvular AF. Two independent reviewers screened studies and extracted data. Quality was assessed using Cochrane Risk of Bias tool (RCTs) and Newcastle-Ottawa Scale (observational studies).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf 1,245 identified records, 55 studies met inclusion criteria (15 RCTs, 12 meta-analyses, 8 systematic reviews, 20 cohort studies), with 71,683 patients derived from the four pivotal randomized trials. Standard-dose DOACs reduced stroke/systemic embolism risk by 19% compared to warfarin (HR 0.81, 95% CI 0.74\u0026ndash;0.89) and intracranial hemorrhage by 55% (HR 0.45, 95% CI 0.37\u0026ndash;0.56). All-cause mortality was reduced by 8% (HR 0.92, 95% CI 0.87\u0026ndash;0.97). Among DOACs, apixaban demonstrated the lowest gastrointestinal bleeding risk (HR 0.72\u0026ndash;0.81 vs. other agents). Risk stratification using CHA₂DS₂-VASc and HAS-BLED scores remains essential for individualized decision-making.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eDOACs are superior to warfarin for stroke prevention in most patients with non-valvular AF, with a particularly favorable safety profile regarding intracranial hemorrhage. Individual DOAC selection should be tailored to patient characteristics, comorbidities, and bleeding risk. Special populations require individualized approaches, with careful consideration of renal function, drug interactions, and patient preferences.\u003c/p\u003e","manuscriptTitle":"Anticoagulation Strategies in Atrial Fibrillation: A Systematic Review and Evidence Synthesis of Direct Oral Anticoagulants Versus Warfarin for Stroke Prevention in Non-Valvular Atrial Fibrillation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-05 06:30:07","doi":"10.21203/rs.3.rs-8497769/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f09318bf-d2c8-4ff6-b056-c86583568c75","owner":[],"postedDate":"January 5th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-05T06:30:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-05 06:30:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8497769","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8497769","identity":"rs-8497769","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}