- Question
- Does andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, control hematoma expansion better than usual care in patients with acute intracerebral hemorrhage associated with these drugs?
- Design
- Randomized 1:1, open-label trial with single-blind masking (phase 4) of 530 patients assigned to andexanet (263) or usual care (267). Efficacy was assessed in an interim analysis of 452 patients; safety was assessed in all 530.
- Population
- Patients with acute intracerebral hemorrhage who had taken a factor Xa inhibitor within the preceding 15 hours; atrial fibrillation was the most common indication for anticoagulation.
- Intervention
- Andexanet alfa, given in one of two dosing regimens depending on the factor Xa inhibitor taken and the dose and timing of the last intake.
- Control
- Usual care, meaning any treatment (including none) that the treating clinicians considered appropriate; 85.5% received prothrombin complex concentrate.
- Primary outcome
- Hemostatic efficacy, defined as the combination of hematoma volume expansion â€35% at 12 hours, an NIHSS score increase of less than 7 points at 12 hours, and no rescue therapy between 3 and 12 hours.
- Results
- Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) with andexanet and in 121 of 228 (53.1%) with usual care (adjusted difference 13.4 percentage points; 95% CI 4.6 to 22.2; P = 0.003). The median reduction in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001).
- Safety
- Thrombotic events occurred in 27 of 263 patients (10.3%) with andexanet and in 15 of 267 (5.6%) with usual care (difference 4.6 percentage points; 95% CI 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 6.5% vs. 1.5%. There were no appreciable differences in the modified Rankin scale or in death within 30 days.
- Conclusion
- In factor Xa inhibitor-associated intracerebral hemorrhage, andexanet achieved better control of hematoma expansion than usual care but was associated with more thrombotic events, including ischemic stroke.
- Why it matters
- It provided randomized evidence on a specific reversal agent in intracerebral hemorrhage, showing a hemostatic benefit at the cost of a higher thrombotic risk, which requires weighing both aspects when deciding on its use.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 15, 2026