Impact of oral anticoagulant choice for the secondary prevention of venous thromboembolism on the risk of inpatient bleeding

Richard F. MacLehose, Neil A. Zakai, Rob F. Walker, Alvaro Alonso, Terrence Adams, Pamela L. Lutsey

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Randomized trials suggest that direct oral anticoagulants (DOACs) are at least as effective as warfarin for primary treatment of VTE and that bleeding risk may be lower for some DOACs relative to warfarin. However, there is very little information regarding potential bleeding risks for DOACs versus warfarin in secondary prevention of VTE. Objective: The aim of this study was to compare rates of bleeding events resulting in inpatient admissions between individuals taking apixaban, rivaroxaban, and warfarin for secondary prevention of VTE during the period 2013-2017. Methods: We used the IBM MarketScan Commercial Claims and Encounters Database and Medicare Supplemental and Coordination of Benefits Database (IBM Watson Health, Ann Arbor, MI) to establish a retrospective cohort. Initial venous thrombolism events were defined from medical claims, and follow-up for this cohort began 6 months after the initial event. Bleeding events resulting in inpatient admission were identified from claims data over the subsequent year of secondary prevention. Results: A total of 69 264 individuals were identified for the cohort, with 567 bleeding events. The crude rate of bleeding was highest among warfarin users (1.47/100 person-years; 95% confidence interval [CI], 1.24-1.74) and lower among those on either apixaban (1.00/100 person-years; 95% CI, 0.65-1.54) or rivaroxaban (0.84/100 person-years; 95% CI, 0.66-1.08). In multivariable adjusted Cox models, those on apixaban (hazard ratio [HR], 0.80; 95% CI, 0.50-1.29) and rivaroxaban (HR, 0.81; 95% CI, 0.59-1.09) had somewhat lower rates of bleeding events relative to those on warfarin. Conclusions: We found modest evidence of decreased risk of bleeding for apixaban and rivaroxaban. These estimates were relatively imprecise.

Original languageEnglish (US)
Article numbere12514
JournalResearch and Practice in Thrombosis and Haemostasis
Issue number4
StatePublished - May 2021

Bibliographical note

Funding Information:
This project was supported by NIH grant R01 HL131579. Dr Alonso was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number K24HL148521. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).


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