Key result
Andexanet alfa showed no difference in 90-day mortality compared to 4F-PCC (30.9% vs 36.6%, p=0.35) but significantly increased 30-day thrombotic events (11.4% vs 2.4%, p<0.01).
Why the study?
Andexanet alfa and 4-factor prothrombin complex concentrate are commonly used to reverse factor Xa inhibitor-related intracranial hemorrhage, but comparative real-world data on short-term mortality and thrombotic events in Veterans were needed.
Does andexanet alfa improve mortality or increase thrombotic events compared to 4-factor prothrombin complex concentrate in Veterans with factor Xa inhibitor-related intracerebral hemorrhage?
Cohort (n=350)
Yes
Does andexanet alfa improve mortality or increase thrombotic events compared to 4-factor prothrombin complex concentrate in Veterans with factor Xa inhibitor-related intracerebral hemorrhage?
Absolute Event Rate: 30.9% vs 36.6%
p-value: p=0.35
In Veterans with factor Xa inhibitor-related intracerebral hemorrhage, andexanet alfa does not improve 90-day mortality but significantly increases the risk of 30-day thrombotic events compared to 4-factor prothrombin complex concentrate.
Supports caution with andexanet alfa for reversal; leaves open optimal strategy in randomized trials.
BACKGROUND AND OBJECTIVES: Two hemostatic agents are commonly used to reverse factor Xa (fXa) inhibitor-related intracranial hemorrhage (ICH): andexanet alfa (AA) or 4-factor prothrombin complex concentrate (4F-PCC). We sought evaluate real-world data in Veterans diagnosed with fXa inhibitor-related ICH by comparing short-term mortality and thrombotic events in patients who received AA vs. 4F-PCC. METHODS: This was a national retrospective cohort from the Veteran Health Administration of AA or 4 F-PCC between January 2018 to January 2024.The primary effectiveness endpoint was 90-day mortality. The primary safety endpoint was 30-day thrombotic events (venous thromboembolism, pulmonary embolism, acute ischemic stroke [AIS], myocardial infarction), validated through manual chart review. Propensity score-matched data set was first created to balance AA and 4F-PCC by the significant demographic and clinical variables and then was used to analyze and compare the results using the complete data set. RESULTS: Of 19,015 Veterans with ICH, 664 Veterans received AA (n = 151) or 4F-PCC (n = 513) and 350 Veterans received a fXa inhibitor (AA n = 129; 4F-PCC n = 221). 123 matched subjects were included in the propensity-matched cohort. The AA group was more likely to be on apixaban (AA group 87.8 % vs. 4F-PCC group 77.2 %, p = 0.03). There was no difference in 90-day mortality between groups (30.9 % vs. 36.6 %, p = 0.35). The AA group experienced significantly more 30-day thrombotic events compared to 4F-PCC (11.4 % vs. 2.4 %, p < 0.01) and AIS was significantly more common with AA. CONCLUSION: In Veterans with fXa inhibitor-related ICH receiving AA or 4F-PCC, there was no difference in 90-day mortality. Consistent with previous literature from non-Veterans studies, 30-day thrombotic events were significantly higher in Veterans who received AA, including a significant increase in AIS. This study adds to the growing body of literature demonstrating higher thrombotic risks with AA. Selection of AA should be carefully weighed against the risk of thrombotic events.
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Rech et al. (2025) conducted a cohort in Factor Xa inhibitor-related intracranial hemorrhage (n=350). Andexanet alfa vs. 4-factor prothrombin complex concentrate (4F-PCC) was evaluated on 90-day mortality (p=0.35). Andexanet alfa showed no difference in 90-day mortality compared to 4F-PCC (30.9% vs 36.6%, p=0.35) but significantly increased 30-day thrombotic events (11.4% vs 2.4%, p<0.01).
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