{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:16:41Z","timestamp":1790669801050,"version":"4.1.0"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"01","license":[{"start":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T00:00:00Z","timestamp":1515369600000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TH Open"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pulmonary embolism (PE) studies used direct oral anticoagulants (DOACs) with or without initial heparin. We aimed to (1) evaluate if PE patients benefit from initial heparin; (2) describe patient characteristics in the DOAC studies; and (3) investigate whether the anatomical extent of PE correlates with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, cause of PE, and recurrence rate. Our methods were (1) an indirect meta-analysis comparing the recurrence risk in DOAC-treated patients with or without initial heparin to those patients given heparin\/vitamin K antagonist (VKA). (2) To compare the PE studies, information was extracted on baseline characteristics including anatomical extent. (3) The Hokusai-VTE study was used to correlate anatomical extent of PE with NT-proBNP levels, causes of PE, and recurrent venous thromboembolism (VTE). The meta-analysis included 11,539 PE patients. The relative risk of recurrent VTE with DOACs versus heparin\/VKAs was 0.8 (95% confidence interval [CI]: 0.6\u20131.1) with heparin lead-in and 1.1 (95% CI: 0.8\u20131.5) without heparin. In the DOAC studies, the proportion of patients with extensive PE varied from 24 to 47%. In Hokusai-VTE, NT-proBNP was elevated in 4% of patients with limited and in over 60% of patients with extensive disease. Cause of PE and anatomical extent were not related. Recurrence rates increased from 1.6% with limited to 3.2% with extensive disease in heparin\/edoxaban-treated patients, and from 2.4 to 3.9% in heparin\/warfarin recipients. In conclusion, indirect evidence suggests a heparin lead-in before DOACs may be advantageous in PE. Anatomical extent was related to elevated NT-proBNP and outcome, but not to PE cause.<\/jats:p>","DOI":"10.1055\/s-0037-1615251","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T23:39:40Z","timestamp":1515454780000},"page":"e1-e7","source":"Crossref","is-referenced-by-count":5,"title":["Direct Oral Anticoagulants for Pulmonary Embolism: Importance of Anatomical Extent"],"prefix":"10.1055","volume":"02","author":[{"given":"Marjolein","family":"Brekelmans","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"B\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Clinical Development, Daiichi Sankyo Pharma Development, Edison, New Jersey, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Ageno","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Chen","sequence":"additional","affiliation":[{"name":"Global Medical Affairs, Daiichi Sankyo Inc., Parsippany, New Jersey, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Haematological Medicine, Guy's and St Thomas' Hospitals, King's College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"van Es","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Grosso","sequence":"additional","affiliation":[{"name":"Clinical Development, Daiichi Sankyo Pharma Development, Edison, New Jersey, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andria","family":"Medina","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Raskob","sequence":"additional","affiliation":[{"name":"College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelise","family":"Segers","sequence":"additional","affiliation":[{"name":"Itreas BV, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vanassche","sequence":"additional","affiliation":[{"name":"Vascular Medicine and Haemostasis, University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Verhamme","sequence":"additional","affiliation":[{"name":"Vascular Medicine and Haemostasis, University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Development, Daiichi Sankyo Pharma Development, Edison, New Jersey, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Weitz","sequence":"additional","affiliation":[{"name":"Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2018,1,8]]},"container-title":["TH Open"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0037-1615251.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T19:48:43Z","timestamp":1557172123000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0037-1615251"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":0,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2018,1,8]]},"published-print":{"date-parts":[[2018,1]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0037-1615251","relation":{},"ISSN":["2512-9465"],"issn-type":[{"value":"2512-9465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]}}}