Host: Christian Croll, Emergency Medicine and ICU Pharmacist at University of Iowa Hospital and Clinics.
Speaker: Sarah Josh, PGY2 Emergency Medicine Resident at Detroit Receiving Hospital.
Topic: Analysis of the ANEXA-4 Trial.
Background
Discussion on off-label use of medications.
Question on reversal agents for factor Xa inhibitors: common agents include 4-factor prothrombin complex concentrate (PCC) and Andexanet alpha (ANEXA).
Historical context:
PCC first approved in 2000 (3-factor) and in early 2010s (4-factor).
ANEXA approved in 2018.
Mechanism of Action
4-Factor PCC: Contains factors II, VII, IX, X, and proteins C and S; helps replace clotting factors.
Andexanet Alpha (ANEXA): Activated factor designed to sequester and reduce anticoagulation; FDA-labeled.
Study Reviews
2011 Study: Outside US; proof of concept that PCC can reverse rivaroxaban and dabigatran.
ANEXA A and R Trials: Showed reduction in anti-factor Xa activity with ANEXA in healthy adults.
ANEXA-4 Trial (2019): Focused on adults with acute major bleeding; showed reduction in anti-factor Xa activity and 82% efficacy in hemostasis.
Real World Comparisons
Study (2023): Compared ANEXA and 4-factor PCC in US hospitals; found statistically significant lower in-hospital mortality with ANEXA.
ANEXA-EY Trial Overview
Objective: Assess safety and efficacy of ANEXA vs. usual care in intracerebral hemorrhage.
Inclusion Criteria: Intracerebral hemorrhage, recent factor Xa inhibitor use, onset within 6 hours, specific hematoma volume, NIHSS score < 35.
Intervention: ANEXA vs. usual care (local protocol).
Outcomes
Primary Outcome: Hemostatic efficacy at 12 hours.
Secondary Outcomes: Reduction in anti-factor Xa activity, functional outcomes.
Safety: Thrombotic events, mortality at 30 days.
Results
67% efficacy with ANEXA vs. 53.1% with usual care.
Statistically significant reduction in anti-factor Xa activity with ANEXA.
Higher thrombotic events with ANEXA.
Critiques
Protocol amendments and heterogeneous comparator group.
Possible bias in time to reversal due to ANEXA preparation.
Limited reporting of secondary outcomes.
Conclusion
ANEXA shows hemostatic efficacy but with increased thrombotic events.
Functional outcomes not significantly different.
Decision on formulary inclusion remains debated.
Discussion
Open for questions and further discussion on formulary considerations.
Personal insight: Current data does not support formulary addition of ANEXA based on functional outcome differences.
Final Notes
Podcast disclaimer on general information; not a substitute for professional healthcare advice.
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