{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T22:23:40Z","timestamp":1769811820552,"version":"3.49.0"},"reference-count":23,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Patients with malignancy demonstrate an elevated risk of developing venous thromboembolism (VTE) due to coagulopathy and treatment modalities. Although low-molecular-weight heparin (LMWH) and warfarin have historically been standard therapies, direct oral anticoagulants (DOACs) are increasingly used in this population. Methods: We conducted a Bayesian network meta-analysis to compare the safety and efficacy of apixaban, edoxaban, rivaroxaban, LMWH, and warfarin in cancer-associated VTE. A comprehensive literature search of Embase, Medline, clinical trial registries, and manual sources was performed up to November 2025. The primary outcome was to compare the risk of VTE recurrence across therapies. Secondary outcomes included major bleeding, clinically relevant non-major bleeding (CRNMB), and all-cause mortality. Odds ratios (ORs) with 95% credible intervals (CrIs) were estimated, and treatment rankings were derived using the surface under the cumulative ranking curves (SUCRA) probabilities. Results: Seven randomized controlled trials (RCTs) involving 3325 patients were included. No clear evidence of differences was observed among apixaban, rivaroxaban, edoxaban, low-molecular-weight heparin, and warfarin for VTE recurrence, major bleeding, clinically relevant non-major bleeding, and mortality. For instance, rivaroxaban showed no statistically significant difference in VTE recurrence compared with apixaban (OR 1.13; 95% CrI 0.17\u201312.27), warfarin (OR 0.60; 95% CrI 0.03\u201319.00), edoxaban (OR 0.77; 95% CrI 0.06\u201311.11), or LMWH (OR 0.51; 95% CrI 0.10\u20132.66). Wide credible intervals reflect uncertainty due to the limited number of RCTs and low event rates. Conclusions: This Bayesian network meta-analysis showed no statistically significant differences between therapies with respect to VTE recurrence, bleeding outcomes, and mortality. However, the wide credible intervals indicate limited precision, warranting cautious interpretation of the findings.<\/jats:p>","DOI":"10.3390\/jcm15031090","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:09:22Z","timestamp":1769771362000},"page":"1090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and Efficacy of Direct Oral Anticoagulants Versus Standard Therapy for Venous Thromboembolism in Cancer Patients: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0171-7391","authenticated-orcid":false,"given":"Alaa","family":"Shahbar","sequence":"first","affiliation":[{"name":"Pharmacy Practices Department, College of Pharmacy, Umm Al-Qura University, Taif Road, Alabdiah, Makkah 21955, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabah","family":"Alshahrani","sequence":"additional","affiliation":[{"name":"Asir Health Cluster, Asir Central Hospital, Clinical Pharmacy Department, Abha 62523, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah","family":"Alhifany","sequence":"additional","affiliation":[{"name":"Pharmacy Practices Department, College of Pharmacy, Umm Al-Qura University, Taif Road, Alabdiah, Makkah 21955, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5279-5437","authenticated-orcid":false,"given":"Mohammed","family":"Alnuhait","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, Shaqra University, Al-Dawadmi Campus, Al-Dawadmi 11961, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afnan","family":"Noor","sequence":"additional","affiliation":[{"name":"Pharmaceutical Care Services Department, King Faisal Specialist Hospital and Research Center, Jeddah 23433, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulaali","family":"Almutairi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faisal A.","family":"Alhamdan","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia"},{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia"},{"name":"Pharmaceutical Care Department, Ministry of the National Guard\u2014Health Affairs, Jeddah 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad A.","family":"Alshamrani","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia"},{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia"},{"name":"Pharmaceutical Care Department, Ministry of the National Guard\u2014Health Affairs, Jeddah 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2477-1339","authenticated-orcid":false,"given":"Alqassem Y.","family":"Hakami","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia"},{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S1470-2045(01)00619-2","article-title":"Cancer and the prothrombotic state","volume":"3","author":"Lip","year":"2002","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1080\/17474086.2018.1502082","article-title":"Management and treatment of deep vein thrombosis in special populations","volume":"11","author":"Boon","year":"2018","journal-title":"Expert Rev. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/oncolo\/oyad116","article-title":"Treatment of cancer-associated thrombosis: Recent advances, unmet needs, and future direction","volume":"28","author":"Wang","year":"2023","journal-title":"Oncologist"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.4103\/ija.IJA_734_18","article-title":"Novel reversal agents and laboratory evaluation for direct-acting oral anticoagulants (DOAC): An update","volume":"63","author":"Shah","year":"2019","journal-title":"Indian J. Anaesth."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s11912-023-01428-y","article-title":"Direct oral anticoagulants for cancer-associated venous thromboembolism","volume":"25","author":"Masini","year":"2023","journal-title":"Curr. Oncol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.15420\/ecr.2017:11:2","article-title":"Direct oral anticoagulants: A quick guide","volume":"12","author":"Sikorska","year":"2017","journal-title":"Eur. Cardiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1111\/jth.13153","article-title":"Oral apixaban for the treatment of venous thromboembolism in cancer patients: Results from the AMPLIFY trial","volume":"13","author":"Agnelli","year":"2015","journal-title":"J. Thromb. Haemost."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/jth.14662","article-title":"Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial","volume":"18","author":"McBane","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1056\/NEJMoa1915103","article-title":"Apixaban for the treatment of venous thromboembolism associated with cancer","volume":"382","author":"Agnelli","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1200\/JCO.2018.78.8034","article-title":"Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: Results of a randomized trial (SELECT-D)","volume":"36","author":"Young","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1177\/1708538120971148","article-title":"Efficacy and safety of apixaban in patients with active malignancy and acute deep venous thrombosis","volume":"29","author":"Mokadem","year":"2020","journal-title":"Vascular"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.chest.2021.09.037","article-title":"Rivaroxaban vs. dalteparin in cancer-associated thromboembolism: A randomized trial","volume":"161","author":"Planquette","year":"2022","journal-title":"Chest"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1056\/NEJMoa1711948","article-title":"Edoxaban for the treatment of cancer-associated venous thromboembolism","volume":"378","author":"Raskob","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.thromres.2018.02.144","article-title":"Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer-associated thrombosis (CAT): A systematic review and meta-analysis","volume":"173","author":"Li","year":"2019","journal-title":"Thromb. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1056\/NEJMoa0906598","article-title":"RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism","volume":"361","author":"Schulman","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1161\/CIRCULATIONAHA.113.004450","article-title":"Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis","volume":"129","author":"Schulman","year":"2014","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1160\/TH14-11-0977","article-title":"Treatment with dabigatran or warfarin in patients with venous thromboembolism and cancer","volume":"114","author":"Schulman","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1056\/NEJMoa025313","article-title":"Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer","volume":"349","author":"Lee","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/jama.2015.9243","article-title":"Tinzaparin vs. warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial","volume":"314","author":"Lee","year":"2015","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1001\/jamainternmed.2016.5954","article-title":"Stroke, bleeding, and mortality risks in elderly Medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation","volume":"176","author":"Graham","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1200\/JCO.23.00294","article-title":"Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update","volume":"41","author":"Key","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_22","unstructured":"National Comprehensive Cancer Network (2025, April 30). Cancer-Associated Venous Thromboembolic Disease, Version 1. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/vte.pdf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1090\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:31:51Z","timestamp":1769772711000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":23,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15031090"],"URL":"https:\/\/doi.org\/10.3390\/jcm15031090","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]}}}