ANNEXA-1: Andexanet Alfa Associated with Harm in DOAC Reversal

The Annexa-1 trial fails to demonstrate clinical benefit for Andexanet alfa in patients with factor Xa inhibitor-associated intracerebral hemorrhage, despite its publication in the *New England Journal of Medicine*. While the study reports improved hemostatic efficacy—a surrogate marker—it neglects patient-centered outcomes like functional recovery and survival. Crucially, the data reveals a doubling of thrombotic events, including ischemic strokes and myocardial infarctions, in the treatment group compared to usual care. The trial’s reliance on shifting primary outcomes, pharmaceutical funding, and the exclusion of critical safety data undermine its validity. Furthermore, the high cost of Andexanet alfa, ranging from $30,000 to $50,000 per treatment, lacks justification given the absence of proven clinical improvement and the potential for increased patient harm. These findings highlight a growing disconnect between high-impact journal publications and rigorous, patient-focused clinical evidence.