REBEL Cast ANNEXA-1: Andexanet Alfa Associated with Harm in DOAC Reversal
May 23, 2024
The discussion kicks off with an exploration of the implications of andexanet alfa in treating factor 10A inhibitor-related brain hemorrhages, stressing the need for more research. It critically assesses the drug’s hemostatic efficacy and raises concerns about biases in clinical trials funded by its manufacturer. Key criticisms focus on patient outcomes, with a striking emphasis on the risk of thrombotic events. Finally, the conversation highlights the importance of transparency and ethical standards in medical research.
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Approval Outpaced Solid Evidence
- Andexanet alfa gained rapid use despite limited robust evidence and a 2A guideline recommendation.
- Hemostatic efficacy is a surrogate outcome that may not reflect patient-centered benefit.
Hemtostatic Efficacy Is A Flawed Primary Outcome
- The trial used a composite
Surrogate Endpoints Mislead Outcomes
- Change in hematoma volume is a surrogate frequently cited but weakly linked to patient outcomes.
- Prior reversal agents reduced expansion yet increased mortality, warning against relying on surrogates.
Background: In May of 2018, Andexanet alfa gained accelerated approval by the FDA for the reversal direct oral anticoagulants (DOACs) despite a lack of robust evidence for use. The 2022 AHA/ASA guidelines give the drug a level 2A recommendation and recommend it over the use of 4F-PCC (Greenberg 2022). FDA approval alongside guideline endorsement has ...