Kadek Kristian Dwi Cahya, I Ketut Sumada, Desie Yuliani, Ni Made Kurnia Dwi Jayanthi

Outcomes of reversal therapy with andexanet alfa and 4F-PCC in FXA inhibitor–associated intracranial hemorrhage: a meta-analysis of apixaban and rivaroxaban cases

Introduction

Outcomes of reversal therapy with andexanet alfa and 4f-pcc in fxa inhibitor–associated intracranial hemorrhage: a meta-analysis of apixaban and rivaroxaban cases. Meta-analysis compares Andexanet Alfa vs 4F-PCC for FXA inhibitor-associated ICH. AA offers superior hemostasis for apixaban/rivaroxaban cases; mortality is comparable.

Abstract

Introduction: Intracranial Hemorrhage (ICH) is a severe complication of factor XA (FXA) inhibitors such as apixaban and rivaroxaban. Reversal agents, including Andexanet Alfa (AA) and Four-Factor Prothrombin Complex Concentrate (4F-PCC), are commonly employed, but their comparative efficacy and safety remain uncertain. This research aims to compare the clinical outcomes of AA versus 4F-PCC in patients with FXA inhibitor-associated ICH through a systematic review and meta-analysis. Methods: This study adhered to PRISMA and MOOSE guidelines. A comprehensive search of multiple databases through May 2025 identified randomized controlled trials and prospective cohort studies comparing AA and 4F-PCC in adult patients with apixaban- or rivaroxaban-associated ICH. Primary outcomes included effective hemostasis, 30-day mortality, and thromboembolic events. Risk ratios (RR) and standardized mean differences (SMD) were calculated using random-effects models with Review Manager 5.4. Results: Nine studies were included. AA demonstrated significantly higher effective hemostasis than 4F-PCC (RR 1.21, 95% CI: 1.07–1.37; p = 0.003) with minimal heterogeneity (I² = 0%). No significant difference was found in 30-day mortality (RR 0.70, 95% CI: 0.32–1.54; p = 0.38), although heterogeneity was substantial (I² = 93%). Thromboembolic events were also comparable (RR 0.80, 95% CI: 0.56–1.14; p = 0.21) with low heterogeneity (I² = 0%). Funnel plots showed a low risk of publication bias for baseline variables, but some asymmetry was noted for clinical outcomes. Conclusion: AA appears superior to 4F-PCC in achieving effective hemostasis in FXA inhibitor-associated ICH. High heterogeneity in mortality data and potential publication bias warrant cautious interpretation and further randomized studies.

Review

This systematic review and meta-analysis addresses a critical clinical challenge concerning intracranial hemorrhage (ICH) associated with factor XA (FXA) inhibitors like apixaban and rivaroxaban. Given the severity of this complication and the availability of different reversal agents, namely Andexanet Alfa (AA) and Four-Factor Prothrombin Complex Concentrate (4F-PCC), understanding their comparative efficacy and safety is paramount. The study's objective to rigorously compare the clinical outcomes of AA versus 4F-PCC in this specific patient population fills an important knowledge gap, providing valuable insights for clinical decision-making in a high-stakes scenario. Following PRISMA and MOOSE guidelines, the authors conducted a comprehensive search to identify nine studies, including randomized controlled trials and prospective cohort studies. The meta-analysis revealed that AA significantly outperformed 4F-PCC in achieving effective hemostasis (RR 1.21, 95% CI: 1.07–1.37; p = 0.003) with minimal heterogeneity. However, no significant difference was observed for 30-day mortality (RR 0.70, 95% CI: 0.32–1.54; p = 0.38), which was notably characterized by substantial heterogeneity (I² = 93%). Similarly, thromboembolic event rates were comparable between the two agents (RR 0.80, 95% CI: 0.56–1.14; p = 0.21), with low heterogeneity. The authors also noted some asymmetry in funnel plots for clinical outcomes, suggesting potential publication bias. The strengths of this study lie in its systematic approach and adherence to established reporting guidelines, providing a robust summary of existing evidence on a pressing clinical question. The finding of superior hemostasis with AA is a significant insight for initial management. However, the substantial heterogeneity observed in mortality data, coupled with the potential for publication bias, mandates a cautious interpretation of the overall results, particularly regarding patient survival. While the study suggests a potential advantage for AA in hemostasis, the lack of a definitive mortality benefit and the noted limitations underscore the urgent need for further well-designed, adequately powered randomized controlled trials. These future studies should aim to definitively establish the comparative safety and efficacy profiles of these reversal agents, especially concerning hard outcomes like mortality, to guide future clinical practice.

Full Text

Comments

You need to be logged in to post a comment.