{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:55:50Z","timestamp":1780491350054,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"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: Anticoagulation for venous thromboembolism (VTE) is required for at least three to six months; however, it is advisable to extend the duration in certain cases, in which case a reduced dose of Direct Oral Anticoagulants (DOACs) may be an option. Our objective was to investigate the efficacy and safety of reduced-dose DOACs in extended anticoagulation treatment compared to full doses. Methods and Results: This retrospective single-centre study included 185 patients treated with DOACs for at least 6 months who were divided into two groups: (1) the Full Dose (FD) group (n = 113) and (2) the Reduced Dose (RD) group (n = 72), which included patients treated with Apixaban at 2.5 mg bis in die (BID) and Rivaroxaban at 10 mg once daily (OD). Post-thrombotic syndrome (PTS) and its progression were evaluated. During an overall follow-up of 48.32 \u00b1 29.49 months, no VTE occurred, and no patients experienced major bleeding; clinically relevant non-major bleeding occurred in three patients in each group (2.7% vs. 4.2% in FD vs. RD, respectively, p = 0.57). From baseline to follow-up, the prevalence of PTS was not significantly decreased in either group (FD: 54.9% vs. 51.3%, p = 0.29; RD 51.4% vs. 44.4%, p = 0.12); conversely, the Villalta score values were significantly decreased at the last follow-up (FD: 5.51 \u00b1 4.18 vs. 5.12 \u00b1 4.36, p &lt; 0.001; RD 5.49 \u00b1 4.06 vs. 5.11 \u00b1 3.73, p = 0.006). Conclusion: In this real-world retrospective registry, very long-term extended anticoagulant therapy with DOACs at full or reduced doses showed comparable efficacy, safety, and impact on PTS progression. Larger studies are needed.<\/jats:p>","DOI":"10.3390\/jcm13082394","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T10:53:17Z","timestamp":1713523997000},"page":"2394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Long-Term Efficacy and Safety of Direct Oral Anticoagulants at Reduced Doses in the Secondary Prevention of Venous Thromboembolism and Post-Thrombotic Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3595-3461","authenticated-orcid":false,"given":"Luca","family":"Costanzo","sequence":"first","affiliation":[{"name":"Unit of Angiology, Department of Cardio-Thoraco-Vascular, Policlinico \u201dG. Rodolico-San Marco\u201d University Hospital, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Di Paola","sequence":"additional","affiliation":[{"name":"Unit of Angiology, Department of Cardio-Thoraco-Vascular, Policlinico \u201dG. Rodolico-San Marco\u201d University Hospital, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Pedi","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Failla","sequence":"additional","affiliation":[{"name":"Unit of Angiology, Department of Cardio-Thoraco-Vascular, Policlinico \u201dG. Rodolico-San Marco\u201d University Hospital, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1196-9073","authenticated-orcid":false,"given":"Marco","family":"Mangiafico","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.thromres.2011.02.017","article-title":"Mortality and recurrence after treatment of VTE: Long term follow-up of patients with good life-expectancy","volume":"127","author":"Andresen","year":"2011","journal-title":"Thromb. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1001\/archinte.159.5.445","article-title":"Predictors of survival after deep vein thrombosis and pulmonary embolism: A population-based, cohort study","volume":"159","author":"Heit","year":"1999","journal-title":"Arch. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.thromres.2015.11.033","article-title":"The economic burden of incident venous thromboembolism in the United States: A review of estimated attributable healthcare costs","volume":"137","author":"Grosse","year":"2016","journal-title":"Thromb. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s11239-009-0378-3","article-title":"Incidence rates, clinical profile, and outcomes of patients with venous thromboembolism. The Worcester VTE study","volume":"28","author":"Spencer","year":"2009","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11239-015-1311-6","article-title":"The epidemiology of venous thromboembolism","volume":"41","author":"Heit","year":"2016","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16950","DOI":"10.1136\/bmjopen-2017-016950","article-title":"Long-term risk of recurrence after discontinuing anticoagulants for a first unprovoked venous thromboembolism: Protocol for a systematic review and meta-analysis","volume":"7","author":"Khan","year":"2017","journal-title":"BMJ Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41569-022-00787-6","article-title":"Epidemiology and prevention of venous thromboembolism","volume":"20","author":"Lutsey","year":"2023","journal-title":"Nat. Reviews. Cardiol."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","unstructured":"Makedonov, I., Kahn, S.R., and Galanaud, J.-P. (2020). Prevention and Management of the Post-Thrombotic Syndrome. J. Clin. Med., 9.","DOI":"10.3390\/jcm9040923"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s11239-009-0309-3","article-title":"Incidence and cost burden of post-thrombotic syndrome","volume":"28","author":"Ashrani","year":"2009","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1111\/jth.14548","article-title":"Anticoagulation therapy patterns for acute treatment of venous thromboembolism in GARFIELD-VTE patients","volume":"17","author":"Haas","year":"2019","journal-title":"J. Thromb. Haemost."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejvs.2020.09.023","article-title":"Editor\u2019s Choice\u2014European Society for Vascular Surgery (ESVS) Clinical Practice Guidelines on the Management of Venous Thrombosis","volume":"61","author":"Kakkos","year":"2021","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1182\/bloodadvances.2020001830","article-title":"American Society of Hematology 2020 guidelines for management of venous thromboembolism: Treatment of deep vein thrombosis and pulmonary embolism","volume":"4","author":"Ortel","year":"2020","journal-title":"Blood Adv."},{"key":"ref_15","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): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC)","volume":"41","author":"Konstantinides","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_16","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":"New Engl. J. Med."},{"key":"ref_17","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":"New Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1111\/j.1538-7836.2009.03339.x","article-title":"Measurement properties of the Villalta scale to define and classify the severity of the post-thrombotic syndrome","volume":"7","author":"Kahn","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Stevens, S.M., Woller, S.C., Baumann Kreuziger, L., Doerschug, K., Geersing, G.J., Klok, F.A., King, C.S., Murin, S., Vintch, J.R.E., and Wells, P.S. (2024). Antithrombotic Therapy for VTE Disease: Compendium and Review of CHEST Guidelines 2012\u20132021. Chest.","DOI":"10.1016\/j.chest.2024.03.003"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"578","DOI":"10.7326\/0003-4819-152-9-201005040-00008","article-title":"Systematic review: Case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism","volume":"152","author":"Carrier","year":"2010","journal-title":"Ann. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"f5133","DOI":"10.1136\/bmj.f5133","article-title":"Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: Systematic review and network meta-analysis","volume":"347","author":"Castellucci","year":"2013","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1111\/j.1538-7836.2010.03991.x","article-title":"Risk of recurrent venous thromboembolism after stopping treatment in cohort studies: Recommendation for acceptable rates and standardized reporting","volume":"8","author":"Kearon","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"481","DOI":"10.7326\/0003-4819-149-7-200810070-00008","article-title":"Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism","volume":"149","author":"Verhovsek","year":"2008","journal-title":"Ann. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"j1065","DOI":"10.1136\/bmj.j1065","article-title":"Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: Multinational prospective cohort management study","volume":"356","author":"Rodger","year":"2017","journal-title":"BMJ"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1182\/bloodadvances.2022007973","article-title":"D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: The Apidulcis study","volume":"6","author":"Palareti","year":"2022","journal-title":"Blood Adv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/eurheartj\/ehac776","article-title":"Recurrent venous thromboembolism and bleeding with extended anticoagulation: The VTE-PREDICT risk score","volume":"44","author":"Carrier","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.7326\/M21-1094","article-title":"Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis","volume":"174","author":"Khan","year":"2021","journal-title":"Ann. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1182\/asheducation-2018.1.432","article-title":"Breadth of complications of long-term oral anticoagulant care","volume":"2018","author":"Ageno","year":"2018","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.thromres.2019.02.010","article-title":"XALIA-LEA: An observational study of venous thromboembolism treatment with rivaroxaban and standard anticoagulation in the Asia-Pacific, Eastern Europe, the Middle East, Africa and Latin America","volume":"176","author":"Kreutz","year":"2019","journal-title":"Thromb. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1182\/blood-2014-03-563577","article-title":"Rates, management, and outcome of rivaroxaban bleeding in daily care: Results from the Dresden NOAC registry","volume":"124","author":"Pannach","year":"2014","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.thromres.2016.01.005","article-title":"Extended anticoagulation and mortality in venous thromboembolism. A meta-analysis of six randomized trials","volume":"139","author":"Bova","year":"2016","journal-title":"Thromb. Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Liu, Z., Tan, J., Deng, Y., Hua, L., and Guo, T. (2022). Clinical and Safety Outcomes Associated with Extended Treatment of Venous Thromboembolism: A Network Meta-Analysis. J. Cardiovasc. Dev. Dis., 9.","DOI":"10.3390\/jcdd9120414"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1111\/jth.14949","article-title":"Extended DOAC therapy in patients with VTE and potential risk of recurrence: A systematic review and meta-analysis","volume":"18","author":"Ebraheem","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mai, V., Bertoletti, L., Cucherat, M., Jardel, S., Grange, C., Provencher, S., and Lega, J.C. (2019). Extended anticoagulation for the secondary prevention of venous thromboembolic events: An updated network meta-analysis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214134"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1111\/jth.14156","article-title":"Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: A systematic review and meta-analysis","volume":"16","author":"Vasanthamohan","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1161\/CIR.0000000000000130","article-title":"The postthrombotic syndrome: Evidence-based prevention, diagnosis, and treatment strategies: A scientific statement from the American Heart Association","volume":"130","author":"Kahn","year":"2014","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.thromres.2021.08.021","article-title":"Impact of direct oral anticoagulants on evolution of post-thrombotic syndrome","volume":"207","author":"Francaviglia","year":"2021","journal-title":"Thromb Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/8\/2394\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:31:13Z","timestamp":1760106673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/8\/2394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,19]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["jcm13082394"],"URL":"https:\/\/doi.org\/10.3390\/jcm13082394","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,19]]}}}