Abstract 091: Efficacy and Safety of Andexanet Alpha Versus Four Factor Prothrombin Complex Concentrate for Emergent Reversal of Factor Xa Inhibitor Associated Intracranial Hemorrhage: A Systematic Review and Meta‐Analysis

Abstract

Introduction Factor Xa inhibitors (FXaI) are increasingly used for anticoagulation therapy, yet their association with intracranial hemorrhage poses a significant challenge. While Andexanet alpha (AA) and four factor prothrombin complex concentrate (4F‐PCC) have shown promise in reversing FXaI effects their comparative efficacy and safety remain uncertain. Methods Following the PRISMA guidelines, we conducted a literature search on electronic databases to obtain the relevant studies until 16 th of May 2024. Our primary outcomes were successful anticoagulation reversal, overall mortality including 30‐day and in hospital mortality, and thromboembolic events. Secondary outcomes were length of hospital and ICU stay and hematoma volume expansion. Data was pooled using random effects model. Results We included 16 eligible studies including the ANNEXA‐1 trial with a total of 2977 patients. A statistically significant improvement in hemostatic efficacy rates were in favor of the AA group (RR 1.10, 95% CI [1.01, 1.20], P = 0.02). Lower overall mortality rates were found in the AA group (RR 0.67, 95% CI [0.51, 0.88], P = 0.004). However, no difference was found in 30‐day mortality rates (RR 0.82, 95% CI [0.58, 1.16], P = 0.26). In terms of thromboembolic events, more events were found in the AA group (RR 1.47, 95% CI [1.01, 2.15], P = 0.046). AA was associated with a longer duration of hospital stay compared to 4F‐PCC (MD 0.64, 95% CI [0.07, 1.22], P = 0.03). Neither a significant difference in length of ICU stays (MD 0.25, 95% CI [‐0.36, 0.86], P = 0.41) nor in hematoma volume expansion was reported (MD ‐0.89, 95% CI [‐3.11, 1.34], P = 0.435). Conclusion Our results suggest that AA is superior to 4F‐PCC in enhancing the hemostatic efficacy and reducing the overall and in‐hospital mortality rates. More thromboembolic events are thought to be associated with the use of AA. However, more studies are required to validate whether the better results of AA in improving hemostatic efficacy are enough to make up for their higher cost and their possible risk of thromboembolic events.