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Real-world management of oral factor Xa inhibitor-related bleeds with reversal or replacement agents including andexanet alfa and four-factor prothrombin complex concentrate: a multicenter study

*Author for correspondence: Tel.: (860) 972 2096; Fax: (860) 545 2277;

E-mail Address: craig.coleman@hhchealth.org

Department of Pharmacy Practice, University of Connecticut School of Pharmacy, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269-3092, USA

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Paul P Dobesh

Department of Pharmacy Practice & Science, College of Pharmacy, University of Nebraska Medical Center, 986145 Nebraska Medical Center, Omaha, NE 68198-6145, USA

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Sherry Danese

Outcomes Insights, 2801 Townsgate Road, Suite 330, Westlake Village, CA 91361, USA

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Julie Ulloa

Outcomes Insights, 2801 Townsgate Road, Suite 330, Westlake Village, CA 91361, USA

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Belinda Lovelace

Portola Pharmaceuticals Inc. 270 E. Grand Avenue South San Francisco, CA 94080, USA

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Published Online:3 Jul 2020https://doi.org/10.2217/fca-2020-0073

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Abstract

Aim: We describe the real-world utilization and outcomes associated with managing oral factor Xa inhibitor (FXai)-related major bleeds. Materials & methods: Electronic records from 45 US hospitals were queried (ICD-10-CM billing codes D68.32, T45.515x or T45.525x) to identify major bleed hospitalizations related to FXai use. Patient demographics, bleed type (intracranial hemorrhage, gastrointestinal, critical compartment, traumatic, other), FXai taken, reversal or replacement agents administered (including andexanet alfa, four-factor prothrombin complex concentrate, fresh frozen plasma, others), in-hospital mortality and length of stay were recorded. Results: Of 3030 FXai-related hospitalizations for major bleeds, patients averaged 68 years old and 47% were women. In-hospital mortality was highest for intracranial hemorrhage (23%, n = 507) and lowest for gastrointestinal bleeds (4%, n = 1453). In-hospital mortality was lowest (4%) for bleeds managed with andexanet alfa (n = 342), compared with 10% for four-factor prothrombin complex concentrate (n = 733), 11% for fresh frozen plasma (n = 925) and 8% for both other agents (n = 794) and no agents (n = 438). Median length of stay was 5 days across all agents, while ICU length of stay was shorter andexanet alfa (2 days) compared with other agents (3 days). Conclusion: In-hospital mortality differed by bleed type and agents administered. Andexanet alfa was associated with the lowest rate of in-hospital mortality across all bleed types.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 17, No. 1

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History

Received 15 May 2020

Accepted 11 June 2020

Published online 3 July 2020

Published in print January 2021

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Acknowledgments

The authors are grateful to participating hospitals and pharmacists for their contribution of data.

Financial & competing interests disclosure

This work was supported by Portola Pharmaceuticals, Inc. The funding agency was involved in the study design, interpretation of data, manuscript preparation and the decision to publish, but not in the data collection or analysis. CI Coleman has received research funding and honoraria from Bayer AG, Janssen Scientific Affairs LLC and Portola Pharmaceuticals, Inc. PP Dobesh has served as a consultant for and received honoraria from Boehringer Ingelheim, the Pfizer/BMS alliance, Janssen Pharmaceuticals, Daiichi Sankyo, Inc and Portola Pharmaceuticals. S Danese and J Ulloa are employees of Outcomes Insights. B Lovelace is an employee of Portola Pharmaceuticals, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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