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Andexanet Alfa to Reverse the Effect of Factor Xa Inhibitors in Intracranial Hemorrhage

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Abstract

Andexanet alfa (AA) is a recombinant factor Xa competing for binding with factor Xa inhibitors, thereby reversing their anticoagulation effects. Since 2019, it has been approved for individuals under apixaban or rivaroxaban therapy suffering from life-threatening or uncontrolled bleeding. Apart from the pivotal trial, real-world data on the use of AA in daily clinics are scarce. We reviewed the current literature on patients with intracranial hemorrhage (ICH) and summarized the available evidence regarding several outcome parameters. On the basis of this evidence, we provide a standard operating procedure (SOP) for routine AA application. We searched PubMed and additional databases through 18 January 2023 for case reports, case series, studies, reviews, and guidelines. Data on hemostatic efficacy, in-hospital mortality, and thrombotic events were pooled and compared with the pivotal trial data. While hemostatic efficacy in world-wide clinical routine seems to be comparable to the pivotal trial, thrombotic events and in-hospital mortality appear to be substantially higher. Various confounding factors responsible for this finding such as exclusion and inclusion criteria resulting in a highly selected patient cohort within the controlled clinical trial have to be considered. The SOP provided should support physicians in patient selection for AA treatment as well as facilitate routine use and dosing. This review underlines the urgent need for more data from randomized trials to appreciate the benefit and safety profile of AA. Meanwhile, this SOP should help to improve frequency and quality of AA use in patients suffering from ICH while on apixaban or rivaroxaban treatment.

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Authors and Affiliations

  1. Department of Vascular Neurology, University Medical Center Ljubljana, Zaloška 2, 1000, Ljubljana, Slovenia

    Senta Frol & Janja Pretnar Oblak

  2. Department of Vascular Disorders, University Medical Center Ljubljana, Ljubljana, Slovenia

    Mišo Šabovič

  3. Faculty of Medicine, University of Ljubljana, Zaloška 2, 1000, Ljubljana, Slovenia

    Senta Frol, Janja Pretnar Oblak & Mišo Šabovič

  4. Department of Neurology, Nordwest-Krankenhaus Sanderbusch, Friesland Kliniken GmbH, Sande, Germany

    Pawel Kermer

  5. University Medical Center, Göttingen, Germany

    Pawel Kermer

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  1. Senta Frol
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Correspondence to Senta Frol.

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Conflict of interest

Author S.F. received lecture honoraria and travel support from Boehringer Ingelheim, Pfizer, and Bayer. Author J.P.O. received lecture honoraria and travel support from Boehringer Ingelheim, Pfizer, and Bayer. Author M.Š. received lecture honoraria and travel support from Boehringer Ingelheim, Pfizer, and Bayer. Author P.K. received lecture honoraria and travel support from Boehringer Ingelheim, Pfizer, BMS, and Bayer. Apart from this, they have no competing financial interests or personal relationships that may have influenced the work in this paper.

Authors’ contributions

S.F. and P.K. were responsible for the conception and design of the study. S.F., J.P.O., M.Š., and P.K. participated in data collection, interpretation, drafting, and review of the article and in its final approval.

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Frol, S., Oblak, J.P., Šabovič, M. et al. Andexanet Alfa to Reverse the Effect of Factor Xa Inhibitors in Intracranial Hemorrhage. CNS Drugs 37, 477–487 (2023). https://doi.org/10.1007/s40263-023-01006-7

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