{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T04:58:53Z","timestamp":1762059533708,"version":"build-2065373602"},"reference-count":18,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) who received off-label rivaroxaban, and to compare their 3-month outcomes with those receiving the labeled therapy. The patients were classified into four subgroups: (1) labeled therapy; (2) delayed start; (3) low doses and (4) both conditions. Results: From May 2013 to May 2022, 2490 patients with PE received rivaroxaban: labeled therapy\u20141485 (58.6%); delayed start\u2014808 (32.5%); low doses\u2014143 (5.7%); both conditions\u201454 (2.2%). Patients with a delayed start were more likely to present with syncope, hypotension, raised troponin levels and more severe abnormalities on the echocardiogram than those on labeled therapy. Patients receiving low doses were most likely to have cancer, recent bleeding, anemia, thrombocytopenia or renal insufficiency. During the first 3 months, 3 patients developed PE recurrence, 4 had deep-vein thrombosis, 11 had major bleeding and 16 died. The rates of major bleeding (11 vs. 0; p &lt; 0.001) or death (15 vs. 1; OR: 22.5; 95% CI: 2.97\u2013170.5) were higher in patients receiving off-label rivaroxaban than in those on labeled therapy, with no differences in VTE recurrence (OR: 1.11; 95% CI: 0.25\u20136.57). Conclusions: In patients with severe PE, the start of rivaroxaban administration was often delayed. In those at increased risk for bleeding, it was often prescribed at low doses. Both subgroups had a worse outcome than those on labeled rivaroxaban.<\/jats:p>","DOI":"10.3390\/life12081128","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T03:21:16Z","timestamp":1658978476000},"page":"1128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-4598","authenticated-orcid":false,"given":"Pierpaolo","family":"Di Micco","sequence":"first","affiliation":[{"name":"UOC Medicina y Urgencia\u2014ASL NAPOLI 2 Nord Ospedale Anna Rizzoli di Lacco Ameno, 34110 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5039-6638","authenticated-orcid":false,"given":"Vladimir","family":"Salazar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Virgen de Arrixaca, 30627 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Capitan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario La Paz, 28015 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Dentali","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Insubria University, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Covadonga","family":"Cuervo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario 12 de Octubre, 28015 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Complejo Hospitalario de Ja\u00e9n, 23160 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose","family":"Porras","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Joan XXIII de Tarragona, 43003 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6566-9029","authenticated-orcid":false,"given":"Angeles","family":"Fidalgo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario de Salamanca, 37004 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvira","family":"Grandone","sequence":"additional","affiliation":[{"name":"Atherosclerosis and Thrombosis Unit, Casa Sollievo Della Sofferenza, 71121 Foggia, Italy"},{"name":"Medical and Surgical Sciences Dept., University of Foggia, 71121 Foggia, Italy"},{"name":"Ob\/Gyn Dept., First Moscow State Medical University, 101000 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Meseguer","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Hospital Universitario Vall d\u2019Hebron, 08016 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-0767","authenticated-orcid":false,"given":"Manuel","family":"Monreal","sequence":"additional","affiliation":[{"name":"Chair for the Study of Thromboembolic Disease, Faculty of Health Sciences, UCAM\u2014Universidad Cat\u00f3lica San Antonio de Murcia, 30627 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the RIETE Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S0140-6736(98)07534-5","article-title":"Acute pulmonary embolism: Clinical outcomes in the International Cooperative Pulmonary Embolism Registry","volume":"353","author":"Goldhaber","year":"1999","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1182\/bloodadvances.2020001830","article-title":"American Society of Hematology 2020 guidelines for the management of venous thromboembolism: Treatment of deep vein thrombosis and pulmonary embolism","volume":"4","author":"Ortel","year":"2020","journal-title":"Blood Adv."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"EINSTEIN-PE Investigators (2012). Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N. Engl. J. Med., 366, 1287\u20131297.","DOI":"10.1056\/NEJMoa1113572"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.chest.2022.01.033","article-title":"Off-label use and inappropriate dosing of direct oral anticoagulants in cardiopulmonary disease","volume":"161","author":"Hussein","year":"2022","journal-title":"Chest"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1080\/14779072.2021.2013816","article-title":"Off-label direct oral anticoagulants dosing in atrial fibrillation and venous thromboembolism is associated with higher mortality","volume":"19","author":"Aguilar","year":"2021","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s10143-021-01539-9","article-title":"Direct oral anticoagulants vs. low-molecular-weight heparin for pulmonary embolism in patients with glioblastoma","volume":"45","author":"Dubinski","year":"2022","journal-title":"Neurosurg. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1007\/s11239-020-02095-7","article-title":"Use of apixaban and rivaroxaban in young adults with acute venous thromboembolism: A multi-center retrospective case series","volume":"50","author":"Ellsworth","year":"2020","journal-title":"J. Thromb. Thrombolysis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/s11239-019-01904-y","article-title":"Real-world assessment of off-label direct oral anticoagulant dosing for venous thromboembolism","volume":"48","author":"Saunders","year":"2019","journal-title":"J. Thromb. Thrombolysis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1160\/TH16-07-0494","article-title":"Real-life treatment of venous thromboembolism with direct oral anticoagulants: The influence of dosing and regimens","volume":"117","author":"Dentali","year":"2017","journal-title":"Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e007971","DOI":"10.1161\/CIRCOUTCOMES.121.007971","article-title":"Off-label under- and overdosing of direct oral anticoagulants in patients with atrial fibrillation. A meta-analysis","volume":"14","author":"Zhang","year":"2021","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"581293","DOI":"10.3389\/fphar.2021.581293","article-title":"Real-world prevalence of direct oral anticoagulant off-label doses in atrial fibrillation: An epidemiological meta-analysis","volume":"12","author":"Shen","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e014108","DOI":"10.1161\/JAHA.119.014108","article-title":"Rates of potentially inappropriate dosing of direct-acting oral anticoagulants and associations with geriatric conditions among older patients with atrial fibrillation: The SAGE-AF Study","volume":"9","author":"Sanghai","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/bcp.14127","article-title":"Impact of direct oral anticoagulant off-label doses on clinical outcomes of atrial fibrillation patients: A systematic review","volume":"86","author":"Santos","year":"2020","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.amjmed.2019.01.025","article-title":"Effectiveness and safety of off-label dose-reduced direct oral anticoagulants in atrial fibrillation","volume":"132","author":"Arbel","year":"2019","journal-title":"Am. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e165","DOI":"10.1016\/j.amjmed.2020.09.018","article-title":"High fluctuation between anticoagulants, frequent off-label dosing, and no difference concerning outcomes: Results of a real-life cohort study","volume":"134","author":"Eschler","year":"2021","journal-title":"Am. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1111\/bcp.14535","article-title":"Prescriber compliance to direct oral anticoagulant labels and impact on outcomes in Thailand","volume":"87","author":"Wattanaruengchai","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.amjmed.2019.09.026","article-title":"Oral anticoagulation in patients in the Emergency Department: High rates of off-label doses, no difference in bleeding rates","volume":"133","author":"Eschler","year":"2020","journal-title":"Am. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1160\/TH17-07-0511","article-title":"Rationale, design and methodology of the Computorized Registry of patients with venous thromboembolism (RIETE)","volume":"118","author":"Bikdeli","year":"2018","journal-title":"Thromb. Haemost."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/8\/1128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:57:23Z","timestamp":1760140643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/8\/1128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,27]]},"references-count":18,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["life12081128"],"URL":"https:\/\/doi.org\/10.3390\/life12081128","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2022,7,27]]}}}