{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:04:14Z","timestamp":1770743054496,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019779","name":"Qatar National Library","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019779","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Despite recent advances in clinical therapeutics in patients with venous thromboembolism, uncertainty remains regarding the optimal anticoagulation strategy in patients with intermediate\u2010 to high\u2010risk pulmonary embolism. We aimed to evaluate the direct oral anticoagulants\u2019 effectiveness and safety compared to warfarin in patients with intermediate\u2010 and high\u2010risk pulmonary embolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this meta\u2010analysis, we systematically searched databases PubMed, EMBASE, Web of Science, and the Cochrane Library from their inception to April 30, 2024, for eligible studies that satisfy inclusion criteria. We included both randomized clinical trials and observational studies reporting on patients diagnosed with intermediate\u2010risk or high\u2010risk pulmonary embolism who were prescribed warfarin or direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban). Two independent reviewers extracted relevant data from included studies based on the Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses guideline. Pooled odds ratios were derived from the included studies using the random\u2010effects model. The primary outcomes were the rate of venous thromboembolism recurrence and all\u2010cause mortality. Secondary outcomes were major and minor bleeding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six studies, five observational and one randomized (<jats:italic>n<\/jats:italic>\u00a0=\u00a0553 patients, out of which 45.7% received advanced therapy), were included in our meta\u2010analysis. Direct oral anticoagulants were associated with comparable recurrence and mortality rates versus warfarin (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.15\u20133.43) and (OR 0.57, 95% CI 0.16\u20132.01), respectively. There was no significant difference in the safety outcomes (major and minor bleeding events), with a trend towards a decreased risk among direct oral anticoagulant treated cohorts (OR 0.3, 95% CI 0.08\u20131.1) and (OR 0.64, 95% CI 0.24\u20131.7), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with intermediate\u2010 to high\u2010risk pulmonary embolism, with or without advanced therapy use, stabilized on direct oral anticoagulants, efficacy and safety outcomes were comparable to those on warfarin, with a trend towards less risk of major and minor bleeding events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p>International PROSPERO database number: CRD42024499532<\/jats:p><\/jats:sec>","DOI":"10.1002\/jha2.70031","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T08:15:07Z","timestamp":1749197707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Direct Oral Anticoagulants Compared to Warfarin in Patients with Intermediate\u2010 to High\u2010Risk Pulmonary Embolism: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3229-6825","authenticated-orcid":false,"given":"Mohamed Nabil","family":"Elshafei","sequence":"first","affiliation":[{"name":"Clinical Pharmacy Department Hamad Medical Corporation Doha Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1639-0491","authenticated-orcid":false,"given":"Muhammad","family":"Salem","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department Hamad Medical Corporation Doha Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0141-0721","authenticated-orcid":false,"given":"Mutasem","family":"Almistarihi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department Hamad Medical Corporation Doha Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haider","family":"Alabd","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department Hamad Medical Corporation Doha Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2398-5338","authenticated-orcid":false,"given":"Ahmed","family":"Khalil","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department Hamad Medical Corporation Doha Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2198-5278","authenticated-orcid":false,"given":"Mohammed","family":"Danjuma","sequence":"additional","affiliation":[{"name":"Internal Medicine Department Hamad Medical Corporation Doha Qatar"},{"name":"Weill Cornell Medicine\u2010Qatar Doha Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"e_1_2_13_2_1","volume-title":"StatPearls","author":"Vyas V.","year":"2024"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(16)30514\u20101"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz405"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000707"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e318214914f"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538\u20107836.2011.04388.x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58091186"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH17\u201003\u20100176"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113572"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10153383"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1302097"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1302507"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.10.003"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/10760296231156414"},{"key":"e_1_2_13_16_1","doi-asserted-by":"crossref","unstructured":"S. M.Stevens S. C.Woller L. B.Kreuziger et\u00a0al. \u201cAntithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report \u201d Chest160 no.6(2021):e545\u2013e608 https:\/\/doi.org\/10.1016\/j.chest.2021.07.055.","DOI":"10.1016\/j.chest.2021.07.055"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306638"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0906598"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928"},{"key":"e_1_2_13_20_1","unstructured":"G. A.Wells B.Shea D.O'Connel et\u00a0al. \"The Newcastle\u2010Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta\u2010Analyses \"Ottawa Hospital 2009 https:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp."},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.repc.2017.01.010"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029618755311"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11239\u2010020\u201002045\u20103"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00554\u20102020"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsv.2024.101848"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.592"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(13)62343\u20100"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S56280"}],"container-title":["eJHaem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.70031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T13:23:10Z","timestamp":1750684990000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jha2.70031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jha2.70031"],"URL":"https:\/\/doi.org\/10.1002\/jha2.70031","archive":["Portico"],"relation":{},"ISSN":["2688-6146","2688-6146"],"issn-type":[{"value":"2688-6146","type":"print"},{"value":"2688-6146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2024-11-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70031"}}