Direct Oral Anticoagulants for Pulmonary Embolism: Importance of Anatomical Extent.

Peter Verhamme,Harry Büller,Thomas Vanassche,Jeffrey Weitz,Cathy Chen,Walter Ageno,Andria Medina,Nick Van Es,Michael Grosso,Gary Raskob,George Zhang,Michele Mercuri,Marjolein Brekelmans,Annelise Segers,Alexander Cohen,Philip Wells

doi:10.1055/s-0037-1615251

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.

Highlights

Direct oral anticoagulants (DOACs) are at least as effective as vitamin K antagonists (VKAs) for treatment of venous thromboembolism (VTE), but are more convenient to administer and are associated with less bleeding.[1]
We focused on recurrent VTE, which was defined in a similar fashion in these studies, and compared the rates of recurrence in patients treated with heparin overlapping with a VKA and DOACs with or without a mandatory heparin lead-in
Associations of Anatomical Extent with Right Ventricular Dysfunction, Causes of pulmonary embolism (PE), and Recurrent VTE in the Hokusai-VTE Study Of the 3,319 PE patients in the Hokusai-VTE study, 90% had NTproBNP levels measured as baseline

Summary

Introduction

Direct oral anticoagulants (DOACs) are at least as effective as vitamin K antagonists (VKAs) for treatment of venous thromboembolism (VTE), but are more convenient to administer and are associated with less bleeding.[1] Because of these attributes, current guidelines give preference to the DOACs over heparin/VKAs for VTE treatment in patients without active cancer.[2]. Studies comparing DOACs with heparin/VKAs have either started the DOAC after a mandatory heparin lead-in of at least 5 days, or have adopted an all-oral DOAC regimen.[3,4,5,6,7,8] These approaches have not been directly compared. All-oral regimens of DOACs are available, clinicians are often reluctant to forgo heparin treatment in patients with pulmonary embolism (PE), in those with computed tomographic (CT) evidence of extensive disease and/or right ventricular enlargement.[9,10,11]

Objectives

Methods

Results

Conclusion