In this episode, I’ll discuss andexanet vs. prothrombin complex concentrate for reversal of factor Xa inhibitor-related intracranial hemorrhage.
Direct, randomized comparisons of andexanet vs prothrombin complex concentrate for reversal of factor Xa inhibitor-related intracranial hemorrhage are rare but questions about the effects of these treatments perisist, especially because of the large disparity in cost between andexanet and PCCs.
In an effort to determine the effectiveness and safety of andexanet and prothrombin complex concentrates (PCCs) when administered after intracranial hemorrhage associated with apixaban or rivaroxaban a group of authors published a multicenter retrospective, observational study in Critical Care Medicine. Data from about 1100 patients were analyzed. To be included in this 42-center study, patients needed to have an apixaban or rivaroxaban-related intracranial hemorrhage and receive either andexanet or PCCs. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis. The primary safety outcome was the occurrence of a thrombotic event during their hospital stay.
The definition of good or excellent hemostasis was based on the Sarode criteria (Table 3 of this document) which has been used in most other studies looking at the effectiveness of andexanet or PCCs. Although the definitions are complex, in general excellent hemostasis means bleeding stopped within an hour of the end of the infusion and no further coagulation-related interventions were needed, and good hemostasis extends the timeframe for bleeding to stop up to 4 hours from the end of the infusion.
When analyzing hemostatic efficacy, 87.8% of the andexanet group had good or excellent hemostasis compared to just 81.8% of the PCC group, a difference that was statistically significant.
However when analyzing safety, 7.9% of the andexanet group experienced a thrombotic event compared with just 4.2% in the PCC group, a difference that was also statistically significant.
When sensitivity analysis was applied to the data, there was no difference in hemostatic or thrombotic outcomes between groups.
The authors concluded:
Despite statistically higher odds of achieving hemostatic efficacy with andexanet, we also observed higher odds of a TE with no difference in discharge outcomes observed between groups. When those with more severe neurologic injuries were excluded, efficacy and safety outcomes were similar between treatments.
This data appears to be in line with that from a 2024 RCT published in NEJM which found better control of hematoma expansion with andexanet at the expense of an increase of thrombotic events.
The topic in this episode is inspired by an in-depth training available to members of my Hospital Pharmacy Academy. The Hospital Pharmacy Academy is my online membership site that will teach you practical critical care and hospital pharmacy skills you can apply at the bedside so that you can become confident in your ability to save lives and improve patient outcomes. To get immediate access to this and many other resources to help in your practice, go to pharmacyjoe.com/academy.
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