ANNEXA-I
Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage
On this page
Overview
Andexanet improved hemostatic efficacy versus usual care in factor Xa inhibitor-related ICH, but increased thrombotic events including ischemic stroke.
Clinical takeaway
Andexanet limited hematoma growth better than usual care, mostly PCC, but the tradeoff was more thrombosis, including ischemic stroke, without a clear functional or survival gain.
Key result
Hemostatic efficacy was 67.0% with andexanet vs 53.1% with usual care (adjusted difference 13.4 percentage points; 95% CI 4.6-22.2; p=0.003).
Practice impact
Use andexanet for factor Xa inhibitor-related ICH only after weighing hematoma control against thrombotic risk; usual care was usually PCC.
Evidence
Study design
Randomized 1:1 trial of andexanet versus usual care.
Enrollment
530
Follow-up
Hematoma volume and NIHSS at 12 hours; modified Rankin scale and death within 30 days.
Geography
Not listed
Clinical question
Does andexanet improve hemostatic efficacy compared with usual care in factor Xa inhibitor-associated acute intracerebral hemorrhage?
Population
- Patients with acute intracerebral hemorrhage who had taken a factor Xa inhibitor within 15 hours; atrial fibrillation was the most common indication for anticoagulation.
Intervention
Andexanet.
Comparator
Usual care, which included prothrombin complex concentrate in 85.5% of patients.
Primary outcome
Hemostatic efficacy, defined as hematoma expansion of 35% or less at 12 hours, an NIHSS increase of less than 7 points at 12 hours, and no rescue therapy between 3 and 12 hours.
Andexanet improved hemostatic efficacy compared with usual care but did not produce an appreciable difference in 30-day function or death.
Adjusted risk difference / 13.4 / 95% CI 4.6-22.2 / p=0.003
Key results
- Hemostatic efficacy was achieved in 67.0% with andexanet vs 53.1% with usual care (adjusted difference 13.4 percentage points; 95% CI 4.6-22.2; p=0.003).
- Median reduction in anti-factor Xa activity to the 1-to-2-hour nadir was 94.5% with andexanet vs 26.9% with usual care (p<0.001).
- Modified Rankin scale scores and death within 30 days did not differ appreciably between groups.
Harms
- Thrombotic events occurred in 10.3% with andexanet vs 5.6% with usual care (difference 4.6 percentage points; 95% CI 0.1-9.2; p=0.048).
- Ischemic stroke occurred in 6.5% with andexanet and 1.5% with usual care.
Clinical Use
Practice impact
- Use andexanet for factor Xa inhibitor-related ICH only after weighing hematoma control against thrombotic risk; usual care was usually PCC.
Applicability
- Most applicable to acute ICH after recent factor Xa inhibitor use, when hematoma expansion is the immediate concern.
Limitations
- The primary endpoint was hemostatic efficacy, not disability or death.
- Efficacy was assessed in an interim population of 452 patients, while safety included all 530 enrolled patients.
- Usual care was not observation; most of those patients received prothrombin complex concentrate.
Common misinterpretations
- Better hematoma control is not the same as better recovery; 30-day modified Rankin scores and death did not differ appreciably.
- The comparator was usual care, usually PCC, not 'no reversal.'
Related evidence
Citation
Connolly SJ, Sharma M, Cohen AT, et al. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. N Engl J Med. 2024;390(19):1745-1755. doi:10.1056/NEJMoa2313040
Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke.
- PMID
- 38749032