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

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.

Keywords:

• anticoagulation
• bleeding-related hospitalization
• DOAC andexanet alfa
• four-factor prothrombin complex concentrate
• FXa inhibitor
• gastrointestinal bleeds
• intracranial hemorrhage
• real-world

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.