CC-BY 4.0 · TH Open 2018; 02(01): e1-e7
DOI: 10.1055/s-0037-1615251
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Direct Oral Anticoagulants for Pulmonary Embolism: Importance of Anatomical Extent

Marjolein P. A. Brekelmans
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
,
Harry R. Büller
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
,
Michele F. Mercuri
Clinical Development, Daiichi Sankyo Pharma Development, Edison, New Jersey, United States
,
Walter Ageno
Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
Cathy Z. Chen
Global Medical Affairs, Daiichi Sankyo Inc., Parsippany, New Jersey, United States
,
Alexander T. Cohen
Department of Haematological Medicine, Guy's and St Thomas' Hospitals, King's College London, London, United Kingdom
,
Nick van Es
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
,
Michael A. Grosso
Clinical Development, Daiichi Sankyo Pharma Development, Edison, New Jersey, United States
,
Andria P. Medina
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
,
Gary Raskob
College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
,
Annelise Segers
Itreas BV, Amsterdam, The Netherlands
,
Thomas Vanassche
Vascular Medicine and Haemostasis, University of Leuven, Leuven, Belgium
,
Peter Verhamme
Vascular Medicine and Haemostasis, University of Leuven, Leuven, Belgium
,
Philip S. Wells
Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada
,
George Zhang
Clinical Development, Daiichi Sankyo Pharma Development, Edison, New Jersey, United States
,
Jeffrey I. Weitz
Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, Ontario, Canada
› Author Affiliations
Further Information

Publication History

29 June 2017

13 November 2017

Publication Date:
08 January 2018 (online)

Abstract

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]: 0.6–1.1) with heparin lead-in and 1.1 (95% CI: 0.8–1.5) 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.

Authors' Contributions

M.P.A.B., H.R.B., M.F.M., and J.I.W. were responsible for conception and design or analysis and interpretation of data, or both. All authors had full access to the data and contributed to drafting of the manuscript or revising it critically for important intellectual content and provided final approval of the manuscript submitted.


Funding

This study was performed without financial support. Four authors are employees of the sponsor of the original Hokusai-VTE study, Daiichi Sankyo, who provided data from the Hokusai-VTE study without restrictions.