{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:19:15Z","timestamp":1786378755545,"version":"build-2736575974"},"reference-count":13,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:00:00Z","timestamp":1768608000000},"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: Venous thromboembolism (VTE) is still a serious clinical problem because many patients still have a significant chance of having it happen again after their first course of anticoagulation is over. In recent years, reduced-dose direct oral anticoagulants (DOACs) have been investigated as a means to ensure prolonged protection while diminishing the risk of bleeding complications. This systematic review aims to summarize the available evidence comparing reduced-dose and full-dose DOAC regimens during the extended phase of VTE treatment. Methods: A systematic search of PubMed and the Cochrane Library (January 2010\u2013November 2025) identified randomized trials and one ambispective cohort study evaluating reduced-dose apixaban (2.5 mg BID), rivaroxaban (10 mg OD), dabigatran (110 mg BID), or edoxaban (30 mg OD). Methodological quality was assessed using RoB-2 for trials and the Newcastle\u2013Ottawa Scale for observational data. Because of differences in study designs and outcome definitions, a narrative synthesis was applied. Results: Five studies met the inclusion criteria. Across trials, reduced-dose DOACs maintained consistently low rates of recurrent VTE: 1.7% in AMPLIFY-EXT versus 8.8% with placebo; 1.2\u20131.5% in EINSTEIN CHOICE versus 4.4% with aspirin; 2.2% in RENOVE versus 1.8% with full-dose therapy; and 1.3% in HI-PRO versus 10% with placebo. Real-world data from Valeriani et al. showed only a single recurrence (0.7%) over nearly three years. Major bleeding remained uncommon, ranging from 0.1 to 0.5% in randomized trials and 2.1\u20132.9% in longer-term observational cohorts. Conclusions: In summary, reduced-dose DOACs appear to offer a favorable balance of safety and efficacy, providing durable protection against recurrence with a lower bleeding burden. These findings support their role as a practical extended-treatment strategy in clinical practice.<\/jats:p>","DOI":"10.3390\/jcm15020770","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:36:33Z","timestamp":1768898193000},"page":"770","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reduced Versus Full-Dose Direct Oral Anticoagulants for Long-Term Management of Venous Thromboembolism: A Systematic Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8084-2181","authenticated-orcid":false,"given":"Manar","family":"Al Arifi","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5180-1952","authenticated-orcid":false,"given":"Walaa A.","family":"Alshahrani","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulmajeed M.","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center (KAIMRC), Riyadh 11481, Saudi Arabia"},{"name":"Ministry of the National Guard-Health Affairs, Riyadh 14611, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-8407","authenticated-orcid":false,"given":"Majed S.","family":"Al Yami","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center (KAIMRC), Riyadh 11481, Saudi Arabia"},{"name":"Ministry of the National Guard-Health Affairs, Riyadh 14611, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S495","DOI":"10.1016\/j.amepre.2009.12.017","article-title":"Venous thromboembolism: A public health concern","volume":"38","author":"Beckman","year":"2010","journal-title":"Am. 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Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0140-6736(24)02842-3","article-title":"Reduced-dose versus full-dose direct oral anticoagulants for extended treatment of venous thromboembolism (RENOVE Trial)","volume":"405","author":"Couturaud","year":"2025","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1056\/NEJMoa2509426","article-title":"Apixaban for Extended Treatment of Provoked Venous Thromboembolism (HI-PRO Trial)","volume":"393","author":"Piazza","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Valeriani, E., Pannunzio, A., Brogi, T., Palumbo, I.M., Menichelli, D., Marucci, S., Tretola, L., Mastroianni, C.M., Pastori, D., and Pignatelli, P. (2025). Three Year Follow-Up of Reduced Dose of Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism: An Ambispective Cohort Study. 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Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/770\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:57:06Z","timestamp":1768899426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/770"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,17]]},"references-count":13,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["jcm15020770"],"URL":"https:\/\/doi.org\/10.3390\/jcm15020770","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,17]]}}}