Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study

Abstract

Background: Intracranial hemorrhage (ICH) is associated with high mortality and morbidity, especially in patients under anticoagulative treatment. Andexanet alfa (AA) is a modified recombinant form of human factor Xa (FXa) developed for reversal of FXa-inhibitors, e.g., in the event of ICH, but experience is still limited. Methods: This monocentric retrospective observational cohort study included 46 patients with acute FXa-inhibitor-associated non-traumatic ICH (FXa-I-ICH) of whom 23 were treated with AA within 12 h after symptom onset, compared to 23 patients with usual care (UC). Volumetrically analyzed hematoma expansion (HE) in brain imaging, clinical outcome and incidence of adverse events were analyzed. Results: All patients (mean age 79.8 ± 7.2 years) were effectively anticoagulated. The cohort included severely ill patients with large hematoma volumes (median 20.4, IQR 7.8–39.0 mL). Efficacy, as assessed by HE in imaging, was very good in the AA-group. There was no (0.0%) relevant HE (>33%) in contrast to UC-group (26.1%). Nevertheless, we observed a high incidence of thromboembolic events (30.4% vs. 4.4%) and non-favorable outcomes (death/palliative condition) in 43.5% vs. 26.1%. Conclusions: There was no HE in the volumetric neuroimaging assessment in the AA-group, but clinical outcomes remained often worse. Large randomized trials for the use of AA in patients with acute FXa-inhibitor-associated ICH are needed to investigate the clinical outcome in consideration of the rates of thromboembolism.

Activated Prothrombin Complex Concentrates for the Treatment of Factor Xa Inhibitor-Associated Spontaneous Intracerebral Hemorrhage

“…However, more patients in the andexanet alfa group died or received palliative care (43.5%) versus the usual care group (26.1%). 18 The mortality rates in this trial were similar to what we found in our study.…”

“…The mortality seen in our study is similar to the morality seen in the trial by Xian and colleagues, 17 where approximately 27% of ICH patients on a factor Xa inhibitor experienced mortality. Overall, 910 of 9202 (53.4%, proportion modified due to missing values) ICH patients taking a factor Xa inhibitor prior to admission received treatment with a prothrombin complex concentrate in the trial by Xian et al Rauch et al 18 compared treatment with andexanet alfa to usual care, including PCC, in patients with factor Xa inhibitor-associated ICH. In the 23 patients with an ICH due to a factor Xa inhibitor, 6 of 23 (26.1%) in the usual care group had ICH volume expansion greater than 33%, compared with 0% with andexanet alfa.…”

Treatment of Factor-Xa Inhibitor-associated Bleeding with Andexanet Alfa or 4 Factor PCC: A Multicenter Feasibility Retrospective Study

“…[24][25][26] Most of these studies have been single-arm, single-center, or both. 6,7,11,12,16,[27][28][29][30][31][32][33][34][35] Some use historical rather than contemporary controls, or at best indirectly compared two independent datasets trying to account for major baseline differences by using a suboptimal PSM. 13 Other studies used propensity score treatment weighting rather than PSM and were able to account for bleed size/volume, which was not captured in the ORANGE indirect comparison.…”