Comparison of outcomes between andexanet alfa and four-factor prothombin complex concentrate for oral Factor Xa inhibiors in patients with non-surgical intracranial hemorrhage: a retrospective review

Introduction: DOACs became the treatment of choice for most thromboembolic diseases. Their favorable safety profile is, however, offset by the lack of a reliable reversal strategy. Andexanet alfa is currently the only approved factorX inhibitor reversal agent. Nonetheless, its safety and efficacy is still under investigation. Factor concentrates, particularly 4F-PCC, are commonly used off-label for the management of major DOAC related bleeding. In this review we summarize our neurocritical care experience with direct FactorX inhibitors reversal.

Methods: This is a retrospective review of patients who were maintained on oral factorX inhibitors when they presented between 2019-2022 with intracranial hemorrhage and received andexanet-alfa or 4F-PCC. All the patients were treated in an academic healthcare network in the state of New York. 14 patients were excluded because of their baseline medical comorbidities. 38 patients who required surgical treatment were also excluded from this study.

Results: 249 patients were available for analysis. 135 (54.2%) received 4F-PCC. The average 4F-PCC dose was 29.41 units/kg. 82.5% of the andexanet alfa group received the low-dose regimen. Both groups were similar in terms of age, sex, concurrent use of an antiplatelet medication, primary type of bleed, baseline hematoma volume, time from ictus to administration and baseline clinical scores (NIHSS, GCS, mRS and ICH). Patients who received 4F-PCC were more likely to have a history of MI or Afib. They also had a worse baseline eGFR.

The mortality rate (p=0.39) and the likelihood of hematoma expansion (p=0.56) were similar between the two groups. However, patients who received andexanet alfa had worse NIHSS and mRS scores on discharge, and lower chance of being discharged home or to inpatient rehabilitation (p=0.044). Andexanet use remained significant in the binary logestic regression model (p=0.001). Other predictors of worse outcome were a history of MI or DM, and worse GCS on presentation.

Conclusion : In this retrospective review, using andexanet alfa did not improve radiological stability or the mortality rate of intracranial hemorrhage and was associated with lower chances of disposition to home or inpatient rehabilitation.