{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:53:56Z","timestamp":1768996436624,"version":"3.49.0"},"reference-count":27,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Few data are available on the outcomes of patients with venous thromboembolism (VTE) on long-term reduced dose of direct oral anticoagulants (DOACs). We evaluated the effectiveness and safety of reduced dose of DOACs for the extended treatment of VTE. Methods: In this monocenter, ambispective cohort study, 140 patients receiving a reduced dose of DOACs for VTE were included. The primary outcomes were recurrent VTE, major bleeding and clinically relevant non-major bleeding. The secondary outcomes were arterial events and minor bleedings. The incidence of the primary outcomes was calculated. The rate for secondary outcomes was descriptively reported. Results: The mean age of the overall cohort was 72 years. Half of the patients were female, 51.4% had a persistent risk factor, 40.0% an unprovoked VTE, and 8.6% a minor transient risk factor. Most patients had lower extremity deep vein thrombosis with or without pulmonary embolism (55.0%) and received apixaban (73.6%) or rivaroxaban (14.3%) for a mean duration of 2.7 years. Regarding the primary outcomes, there was one recurrent VTE (0.7%), four major bleedings (2.9%) and two clinically relevant non-major bleedings (1.4%). Regarding the secondary outcomes, there were four acute ischemic strokes (2.9%) and two minor bleedings (1.4%). Conclusions: Reduced dose of DOACs was associated with a low rate of recurrent VTE and an acceptably low rate of bleeding complications. The rate of arterial events during follow-up suggests the need for an assessment of cardiovascular risk factors in this study population.<\/jats:p>","DOI":"10.3390\/diagnostics15172283","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T08:40:15Z","timestamp":1757407215000},"page":"2283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Three Year Follow-Up of Reduced Dose of Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism: An Ambispective Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-3214","authenticated-orcid":false,"given":"Emanuele","family":"Valeriani","sequence":"first","affiliation":[{"name":"Department of General Surgery and Surgical Specialty, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"Department of Infectious Disease, Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-7626","authenticated-orcid":false,"given":"Arianna","family":"Pannunzio","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Specialty, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3426-9050","authenticated-orcid":false,"given":"Tommaso","family":"Brogi","sequence":"additional","affiliation":[{"name":"Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5749-786X","authenticated-orcid":false,"given":"Ilaria Maria","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Specialty, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-5903","authenticated-orcid":false,"given":"Danilo","family":"Menichelli","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Specialty, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Marucci","sequence":"additional","affiliation":[{"name":"Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Tretola","sequence":"additional","affiliation":[{"name":"Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1286-467X","authenticated-orcid":false,"given":"Claudio Maria","family":"Mastroianni","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Umberto I Hospital, Viale del Policlinico 155, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-5213","authenticated-orcid":false,"given":"Daniele","family":"Pastori","sequence":"additional","affiliation":[{"name":"Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-7455","authenticated-orcid":false,"given":"Pasquale","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"I4","DOI":"10.1161\/01.CIR.0000078468.11849.66","article-title":"The epidemiology of venous thromboembolism","volume":"107","author":"White","year":"2003","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103447","DOI":"10.1016\/j.autrev.2023.103447","article-title":"Risk of venous thromboembolism in autoimmune diseases: A comprehensive review","volume":"22","author":"Menichelli","year":"2023","journal-title":"Autoimmun. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pastori, D., Cormaci, V.M., Marucci, S., Franchino, G., Del Sole, F., Capozza, A., Fallarino, A., Corso, C., Valeriani, E., and Menichelli, D. (2023). A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043169"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e545","DOI":"10.1016\/j.chest.2021.07.055","article-title":"Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report","volume":"160","author":"Stevens","year":"2021","journal-title":"Chest"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"l4363","DOI":"10.1136\/bmj.l4363","article-title":"Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: Systematic review and meta-analysis","volume":"366","author":"Khan","year":"2019","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/eurheartj\/ehz405","article-title":"2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)","volume":"41","author":"Konstantinides","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e419S","DOI":"10.1378\/chest.11-2301","article-title":"Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines","volume":"141","author":"Kearon","year":"2012","journal-title":"Chest"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"ITC129","DOI":"10.7326\/AITC202209200","article-title":"Deep Venous Thrombosis","volume":"175","author":"Duffett","year":"2022","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1182\/blood-2014-04-571232","article-title":"Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: Evidence from phase 3 trials","volume":"124","author":"Coppens","year":"2014","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1055\/a-2497-4089","article-title":"Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe","volume":"125","author":"Agnelli","year":"2025","journal-title":"Thromb. Haemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1207541","article-title":"Apixaban for extended treatment of venous thromboembolism","volume":"368","author":"Agnelli","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa1700518","article-title":"Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism","volume":"376","author":"Weitz","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.chest.2024.03.003","article-title":"Antithrombotic Therapy for VTE Disease: Compendium and Review of CHEST Guidelines 2012\u20132021","volume":"166","author":"Stevens","year":"2024","journal-title":"Chest"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0140-6736(24)02842-3","article-title":"Extended treatment of venous thromboembolism with reduced-dose versus full-dose direct oral anticoagulants in patients at high risk of recurrence: A non-inferiority, multicentre, randomised, open-label, blinded endpoint trial","volume":"405","author":"Couturaud","year":"2025","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Poli, D., Parisi, R., Antonucci, E., Barcella, L., Bucherini, E., Chistolini, A., Di Giorgio, A., Di Giulio, R., Di Nisio, M., and Elmi, G. (2025). Low-dose of direct oral anticoagulants for secondary prevention in patients at high risk for recurrence due to history of recurrent venous thromboembolic events or to severe thrombophilia: A retrospective analysis of the Italian START2 Registry. J. Thromb. Haemost., in press.","DOI":"10.1016\/j.jtha.2025.07.034"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"61","author":"Altman","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1111\/jth.13336","article-title":"Categorization of patients as having provoked or unprovoked venous thromboembolism: Guidance from the SSC of ISTH","volume":"14","author":"Kearon","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1538-7836.2005.01204.x","article-title":"Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients","volume":"3","author":"Schulman","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1111\/jth.13140","article-title":"Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: Communication from the SSC of the ISTH","volume":"13","author":"Kaatz","year":"2015","journal-title":"J. Thromb. Haemost."},{"key":"ref_20","unstructured":"R Core Team (2019). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.r-project.org\/."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102194","DOI":"10.1016\/j.eclinm.2023.102194","article-title":"The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: A systematic review and meta-analysis","volume":"64","author":"Nasserinejad","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5595","DOI":"10.1182\/bloodadvances.2020002268","article-title":"Which patients are at high risk of recurrent venous thromboembolism (deep vein thrombosis and pulmonary embolism)?","volume":"4","author":"Ainle","year":"2020","journal-title":"Blood Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1016\/S0735-1097(23)02512-3","article-title":"Cardiovascular Events in Patients with VTE: A Cohort Study in Region Stockholm","volume":"81","author":"Siddiqui","year":"2023","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"683","DOI":"10.2147\/CLEP.S481448","article-title":"Risk of Venous Thromboembolism in Statin Users Compared to Fibrate Users in the United Kingdom Clinical Practice Research Datalink (UK CPRD) GOLD","volume":"16","author":"Ayodele","year":"2024","journal-title":"Clin. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s11239-024-03002-0","article-title":"Statins use and recurrent venous thromboembolism in the direct oral anticoagulant era: Insight from the COMMAND VTE Registry-2","volume":"57","author":"Mabuchi","year":"2024","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1093\/eurheartj\/ehae361","article-title":"Lipid lowering for prevention of venous thromboembolism: A network meta-analysis","volume":"45","author":"Farmakis","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1111\/jth.14807","article-title":"Impact of concomitant antiplatelet therapy on the efficacy and safety of direct oral anticoagulants for acute venous thromboembolism: Systematic review and meta-analysis","volume":"18","author":"Valeriani","year":"2020","journal-title":"J. Thromb. Haemost."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2283\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:42:19Z","timestamp":1760035339000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":27,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["diagnostics15172283"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15172283","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,8]]}}}