Time to hemostatic agent administration increases mortality in veterans with factor Xa inhibitor-related intracranial hemorrhage.

Markovic N, Budde E, Evans CT, Finch D, Xia Y, Huo Z, Han JH, Rech MA. Time to hemostatic agent administration increases mortality in veterans with factor Xa inhibitor-related intracranial hemorrhage. The American journal of emergency medicine. 2025 Aug 23; 98:201-206, DOI: 10.1016/j.ajem.2025.08.047.

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Abstract:

BACKGROUND: The two hemostatic agents utilized for reversal of life-threatening hemorrhage associated with Factor Xa (fXa) inhibition are andexanet alfa (AA) and four-factor prothrombin complex concentrate (4F-PCC). In May 2018, AA was approved with possible superior short-term hemostatic efficacy but has been linked with higher rates of thrombotic events. Considering these concerns, the absence of high-quality comparative studies, and the higher cost compared to other agents, four-factor prothrombin complex concentrate remained the more utilized agent. There is a critical need for real-world data from large-scale databases describing the reversal of fXa inhibitors using AA compared to 4F-PCC to determine their time to hemostatic treatment and its effect on patient outcomes and mortality. METHODS: This was a national retrospective cohort from the Veteran Health Administration of AA or 4 F-PCC usage between January 1, 2018 to January 1, 2024. The primary endpoint was time to hemostatic treatment. The secondary endpoints were 30-day thrombotic events and 90-day mortality, which were validated through manual chart review. Demographic and treatment variables were summarized using descriptive statistics. The two sample Wilcoxon rank-sum test was utilized on the primary endpoint. A multivariable logistic regression was used to analyze the relationship between 90-day mortality and time to hemostatic treatment. RESULTS: There were 19,015 Veterans with ICH; 246 (AA n  =  89; 4F-PCC n  =  157) of the Veterans that received an fXa inhibitor within 180 days in the emergency department were included in the study. Most Veterans were male (96.4 %) and elderly. Apixaban was the most utilized anticoagulant, and intracerebral hemorrhage was the most common type of intracranial hemorrhage (ICH). There was no difference in the primary endpoint of time to hemostatic treatment between the groups (AA group median: 203 min (IQR 140-283) vs. 4F-PCC median: 200 min (IQR 137-299), p  =  0.70). 90-day mortality was 19.1 % where the odds of 90-day mortality increased by 0.4 % for each additional minute of time to hemostatic agent administration (odds ratio [OR] 1.004, 95 % confidence interval ([CI] 1.001-1.006). CONCLUSION: In Veterans with fXa inhibitor-related ICH receiving AA or 4F-PCC, there was no difference between AA and 4F-PCC in time to hemostatic treatment. Time to hemostatic agent administration increased odds of 90-mortality by 0.4 % for every minute, but did not differ depending on the hemostatic agent used.