Exploratory secondary analyses of a randomized trial · PMID 42093656
This analysis helps explain which patients had greater risk of hematoma expansion. Its exploratory treatment-selection findings require a separate reading from current U.S. practice: Andexxa is no longer commercially available in the United States.
Read the article record on PubMed
Current U.S. context
The FDA concluded that Andexxa’s serious risks, including thromboembolic events, outweigh its benefits. AstraZeneca ended U.S. commercial sales by December 22, 2025, and stopped manufacturing it for the U.S. market after that date. Read this paper as historical trial evidence, not as a current U.S. treatment pathway. The study’s proposed selection rule does not override that safety assessment.2
What was studied
Investigators analyzed 459 ANNEXA-I participants with qualifying intracerebral hemorrhage and interpretable baseline and follow-up imaging. The parent trial randomized andexanet versus usual care; identifying predictors of expansion within this dataset was observational. Hematoma expansion meant an increase of at least 35% or at least 12.5 mL between baseline and 12-hour imaging. It occurred in 149 patients (32.5%).1
What the findings mean
Shorter symptom-onset-to-treatment time, larger baseline hematoma volume, higher diastolic blood pressure, and faster estimated prescan hematoma growth were associated with subsequent expansion. Prescan growth was calculated as baseline hematoma volume divided by time from symptom onset to the baseline scan; it was not a measured change between two scans. The association with earlier presentation is a marker of expansion risk, not a reason to delay treatment.1
Where the treatment inference stops
Patients with the largest hematomas or fastest estimated growth had numerically greater absolute reductions in expansion with andexanet. These subgroup findings were hypothesis-generating: the analysis could not establish statistically significant treatment interactions. The parent trial was not powered for death or disability. Failure to find an association between these predictors and thrombosis also does not prove that a selected subgroup is safe; thrombotic events were few and follow-up was limited.1
A practical pharmacist action
Application: when reviewing a factor Xa inhibitor–associated intracerebral hemorrhage, organize the anticoagulant and last-dose history, onset and imaging times, imaging findings, and blood-pressure information for the treating team. Escalate through the institution’s current reversal and stroke pathways. These data support a timely risk discussion; they do not establish a new blood-pressure target, a validated treatment-selection cutoff, or an andexanet regimen.1
Sources
- Shoamanesh A, Connolly SJ, Demchuk AM, et al. Predictors of Hematoma Expansion and Response to Andexanet in Patients With Intracerebral Hemorrhage: Secondary Analyses of the ANNEXA-I Randomized Clinical Trial. Stroke. 2026;57(7):1920-1928. doi:10.1161/STROKEAHA.124.050418. PubMed.
- US Food and Drug Administration. Update on the Safety of Andexxa. FDA Safety Communication. December 18, 2025. Accessed September 5, 2026. FDA safety communication.
ACPE UAN: 0683-0000-26-036-H01-P