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. 2018 Jan 8;2(1):e1-e7.
doi: 10.1055/s-0037-1615251. eCollection 2018 Jan.

Direct Oral Anticoagulants for Pulmonary Embolism: Importance of Anatomical Extent

Marjolein P A Brekelmans  1 , Harry R Büller  1 , Michele F Mercuri  2 , Walter Ageno  3 , Cathy Z Chen  4 , Alexander T Cohen  5 , Nick van Es  1 , Michael A Grosso  2 , Andria P Medina  6 , Gary Raskob  7 , Annelise Segers  8 , Thomas Vanassche  9 , Peter Verhamme  9 , Philip S Wells  10 , George Zhang  2 , Jeffrey I Weitz  11
Affiliations

Direct Oral Anticoagulants for Pulmonary Embolism: Importance of Anatomical Extent

Marjolein P A Brekelmans et al. TH Open. .

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.

Keywords: anatomical extent; oral anticoagulants; pulmonary embolism; right ventricular dysfunction; venous thromboembolism.

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Conflict of interest statement

Conflicts of Interest M.P.A.B. has nothing to disclose. H.R.B. reports grants and personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Ionis Pharmaceuticals, Pfizer, Roche, Sanofi, and ThromboGenics outside the submitted work. M.F.M. is an employee of Daiichi-Sankyo Pharma Development. W.A. reports grants, personal fees, and nonfinancial support from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Stago; and personal fees from Bristol-Myers Squibb, Pfizer, and Aspen, outside the submitted work. C.Z.C. is an employee of Daiichi-Sankyo, Inc. A.T.C. reports grants from Daiichi-Sankyo Pharma Development during the conduct of the study; grants and personal fees from Bayer, Bristol-Myers Squibb, and Pfizer; and personal fees from Boehringer Ingelheim, Janssen, Johnson & Johnson, Portola, Sanofi, and XO1 outside the submitted work. N.v.E. reports a personal fee from Pfizer outside the submitted work. M.A.G. is an employee of Daiichi-Sankyo Pharma Development. A.P.M. has nothing to disclose. G.R. reports personal fees from Daiichi-Sankyo and Itreas during the conduct of the study; and personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Ionis Pharmaceuticals, Janssen, Pfizer, and Portola outside the submitted work. A.S. reports grants from Daiichi-Sankyo Pharma Development during the conduct of the study; and grants from Ionis Pharmaceuticals outside the submitted work. T.V. reports grants from Daiichi-Sankyo Pharma Development during the conduct of the study. P.V. reports grants and personal fees from Daiichi-Sankyo Pharma Development during the conduct of the study; and grants from Leo Pharma; grants and personal fees from Boehringer Ingelheim, Sanofi, and ThromboGenics; and personal fees from Bayer outside the submitted work. P.S.W. reports personal fees from Bayer and Daiichi Sankyo; and grants from Bristol-Myers Squibb and Pfizer outside the submitted work. G.Z. is an employee of Daiichi-Sankyo Pharma Development. J.I.W. reports personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis Pharmaceuticals, Janssen, Pfizer, Novartis, and Portola outside the submitted work.

Figures

Fig. 1
Fig. 1
Relative risk of recurrent venous thromboembolism with or without a heparin lead-in. DOAC, direct oral anticoagulant; VKA, vitamin K antagonist.
See this image and copyright information in PMC

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