{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:58:24Z","timestamp":1790697504488,"version":"4.1.0"},"reference-count":39,"publisher":"IMR Press","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Cardiovasc. Med."],"abstract":"<jats:p>Background: Patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) face a markedly elevated risk of both thromboembolic and bleeding events. While oral anticoagulation is the cornerstone of stroke prevention in AF, the optimal use of this treatment in patients with stage 4\u20135 CKD and end-stage renal disease (ESRD) undergoing dialysis remains uncertain, as these populations were largely excluded from the landmark trials that established the efficacy of direct oral anticoagulants (DOACs) in the general AF population. This study aimed to systematically evaluate and compare the efficacy and safety of vitamin K antagonists (VKAs) and DOACs, including factor Xa inhibitors, compared with alternative anticoagulation strategies or no anticoagulation in patients with AF and advanced CKD, including both non-dialysis-dependent stage 4\u20135 CKD and dialysis-dependent ESRD. Methods: A systematic search of PubMed (MEDLINE), the Cochrane Library, and ClinicalTrials.gov was performed through January 30, 2026. Randomized controlled trials and observational cohort studies evaluating oral anticoagulation in adults with AF and stage 4\u20135 CKD (estimated glomerular filtration rate (eGFR) &lt;30 mL\/min\/1.73 m2, not on dialysis) or ESRD on dialysis were included. Outcomes of interest were a composite of stroke, transient ischemic attack or systemic embolism, major bleeding (International Society on Thrombosis and Haemostasis (ISTH) or study-defined), and all-cause mortality. Owing to clinical and methodological heterogeneity, evidence was synthesized narratively for most comparisons; randomized trials comparing factor Xa inhibitors with VKAs in dialysis-dependent patients were pooled in a random-effects meta-analysis. Results: A total of 20 studies met the inclusion criteria, comprising four randomized trials, one subgroup analysis of an RCT (ARISTOTLE), and fifteen observational cohorts. Four studies evaluated patients with advanced CKD not receiving dialysis, while sixteen focused on dialysis populations. In non-dialysis stage 4\u20135 CKD, DOAC therapy, particularly apixaban, was generally associated with comparable or reduced thromboembolic risk and lower rates of major bleeding compared with warfarin. Observational data also suggested a potential mortality benefit with DOACs compared with no anticoagulation. In contrast, findings in dialysis-dependent ESRD were heterogeneous. Warfarin was not consistently associated with reduced stroke risk compared with no anticoagulation and was frequently linked to elevated bleeding risk. Observational studies suggest that apixaban may confer a lower risk of major bleeding compared with VKAs while maintaining similar thromboembolic protection; however, randomized evidence has been limited and underpowered to demonstrate a definitive net clinical benefit. In a meta-analysis of the four dialysis randomized trials (n = 486), factor Xa inhibitors were associated with less ISTH major bleeding than VKAs (pooled risk ratio (RR) 0.64, 95% confidence interval (CI) 0.42\u20130.99; not retained in Mantel\u2013Haenszel or Hartung\u2013Knapp sensitivity analyses), with no significant difference in stroke, transient ischemic attack or systemic embolism (pooled RR 0.46, 95% CI 0.20\u20131.02) or all-cause mortality (RR 0.88, 95% CI 0.58\u20131.35). Conclusion: The risk\u2013benefit profile of oral anticoagulation differs across the CKD spectrum. In stage 4\u20135 CKD not requiring dialysis, DOACs appear to offer a more favorable safety profile than VKAs while preserving efficacy. In dialysis-dependent ESRD, the net clinical benefit of anticoagulation remains uncertain, particularly for warfarin. Further adequately powered randomized trials are needed to clarify optimal anticoagulation strategies in this high-risk population. Until then, treatment decisions should remain individualized, balancing thromboembolic and bleeding risk. PROSPERO Registration: https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261286449.<\/jats:p>","DOI":"10.31083\/rcm52237","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:57:11Z","timestamp":1790693831000},"source":"Crossref","is-referenced-by-count":0,"title":["Oral Anticoagulants in Patients With Atrial Fibrillation and Advanced or End-Stage Renal Disease: A Systematic Review and Meta-Analysis"],"prefix":"10.31083","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-6859","authenticated-orcid":true,"given":"Stylianos","family":"Fiflis","sequence":"first","affiliation":[{"name":"Department of Cardiology, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7238-7117","authenticated-orcid":true,"given":"Georgios","family":"Aletras","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2432-7988","authenticated-orcid":true,"given":"Maria","family":"Bachlitzanaki","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1340-2282","authenticated-orcid":true,"given":"Emmanouil","family":"Foukarakis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Venizelio General Hospital of Heraklion, 71409 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Linz D, Gawalko M, Betz K, Hendriks JM, Lip GYH, Vinter N, et al. 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Circulation. 2022; 146: 1735\u20131745.","DOI":"10.1161\/CIRCULATIONAHA.121.054990"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"De Vriese AS, Caluw\u00e9 R, Van Der Meersch H, De Boeck K, De Bacquer D. Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled Trial. Journal of the American Society of Nephrology: JASN. 2021; 32: 1474\u20131483.","DOI":"10.1681\/ASN.2020111566"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Harel Z, Smyth B, Badve SV, Blum D, Beaubien-Souligny W, Silver SA, et al. Anticoagulation for Patients with Atrial Fibrillation Receiving Dialysis: A Pilot Randomized Controlled Trial. Journal of the American Society of Nephrology: JASN. 2025; 36: 901\u2013910.","DOI":"10.1681\/ASN.0000000000000495"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Reinecke H, Engelbertz C, Bauersachs R, Breithardt G, Echterhoff HH, Ger\u00df J, et al. A Randomized Controlled Trial Comparing Apixaban With the Vitamin K Antagonist Phenprocoumon in Patients on Chronic Hemodialysis: The AXADIA-AFNET 8 Study. Circulation. 2023; 147: 296\u2013309.","DOI":"10.1161\/CIRCULATIONAHA.122.062779"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Stanifer JW, Pokorney SD, Chertow GM, Hohnloser SH, Wojdyla DM, Garonzik S, et al. Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease. Circulation. 2020; 141: 1384\u20131392.","DOI":"10.1161\/CIRCULATIONAHA.119.044059"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Ballegaard ELF, Olesen JB, Kamper AL, Feldt-Rasmussen B, Gislason G, Torp-Pedersen C, et al. Oral anticoagulation for stroke prevention in atrial fibrillation and advanced kidney disease. Research and Practice in Thrombosis and Haemostasis. 2024; 8: 102350.","DOI":"10.1016\/j.rpth.2024.102350"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Hsu CC, Chen CC, Chou CY, Chen KH, Wang SF, Chang SL, et al. Effectiveness and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation and advanced kidney disease. Journal of Thrombosis and Thrombolysis. 2023; 56: 518\u2013528.","DOI":"10.1007\/s11239-023-02859-x"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Weir MR, Ashton V, Moore KT, Shrivastava S, Peterson ED, Ammann EM. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and stage IV-V chronic kidney disease. 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Efficacy and safety of apixaban compared to warfarin for nonvalvular atrial fibrillation in end-stage renal disease on hemodialysis. Journal of the American Pharmacists Association: JAPhA. 2024; 64: 457\u2013462.","DOI":"10.1016\/j.japh.2023.12.020"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Siontis KC, Zhang X, Eckard A, Bhave N, Schaubel DE, He K, et al. Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States. Circulation. 2018; 138: 1519\u20131529.","DOI":"10.1161\/CIRCULATIONAHA.118.035418"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"S\u00e1nchez Soriano RM, Albero Molina MD, Chamorro Fern\u00e1ndez CI, Juli\u00e1-Sanch\u00eds R, L\u00f3pez Menchero R, Del Pozo Fern\u00e1ndez C, et al. Long-term prognostic impact of anticoagulation on patients with atrial fibrillation undergoing hemodialysis. 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Association between warfarin use and incidence of ischemic stroke in Japanese hemodialysis patients with chronic sustained atrial fibrillation: a prospective cohort study. Clinical and Experimental Nephrology. 2014; 18: 662\u2013669.","DOI":"10.1007\/s10157-013-0885-6"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Shah M, Avgil Tsadok M, Jackevicius CA, Essebag V, Eisenberg MJ, Rahme E, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation. 2014; 129: 1196\u20131203.","DOI":"10.1161\/CIRCULATIONAHA.113.004777"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Kaisaier W, Chen Y, Lip GYH, Liu C, Zhu W. Safety and Efficacy of Factor Xa Inhibitors in Atrial Fibrillation Patients on Dialysis: Evidence from Four Randomized Controlled Trials. Thrombosis and Haemostasis. 2026; 126: 11\u201322.","DOI":"10.1055\/a-2544-7919"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Rhee TM, Lee SR, Choi EK, Oh S, Lip GYH. Efficacy and Safety of Oral Anticoagulants for Atrial Fibrillation Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Frontiers in Cardiovascular Medicine. 2022; 9: 885548.","DOI":"10.3389\/fcvm.2022.885548"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"de Oliveira HM, Barros LP, de Campos MCAV, Daher RF, Gon\u00e7alves GB, Sequeira MT, et al. Anticoagulation Strategies for Atrial Fibrillation in CKD Stage G5 and Dialysis Patients: An Updated Scoping Review. Reviews in Cardiovascular Medicine. 2025; 26: 26736.","DOI":"10.31083\/RCM26736"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Parker K, Hartemink J, Saha A, Mitra R, Lewis P, Power A, et al. A systematic review of the efficacy and safety of anticoagulants in advanced chronic kidney disease. Journal of Nephrology. 2022; 35: 2015\u20132033.","DOI":"10.1007\/s40620-022-01413-x"}],"container-title":["Reviews in Cardiovascular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/27\/9\/10.31083\/RCM52237","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:57:49Z","timestamp":1790693869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/27\/9\/10.31083\/RCM52237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":39,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026]]}},"alternative-id":["S2153-8174(26)03913-0"],"URL":"https:\/\/doi.org\/10.31083\/rcm52237","relation":{},"ISSN":["1530-6550","2153-8174"],"issn-type":[{"value":"1530-6550","type":"print"},{"value":"2153-8174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"article-number":"52237"}}