A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation

Background Atrial fibrillation (AF) is a leading cause of stroke, necessitating effective anticoagulation. While direct oral anticoagulants (DOACs) have improved stroke prevention, bleeding risks remain a concern. Factor XI/XIa inhibitors, targeting the intrinsic coagulation pathway, offer potential...

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Main Authors: Zhengbiao Xue MS, Song Liao MS, Haiye Fan MS, Yu Shen MS, Zhi Nie MS
Format: Article
Language:English
Published: SAGE Publishing 2025-04-01
Series:Clinical and Applied Thrombosis/Hemostasis
Online Access:https://doi.org/10.1177/10760296251335967
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author Zhengbiao Xue MS
Song Liao MS
Haiye Fan MS
Yu Shen MS
Zhi Nie MS
author_facet Zhengbiao Xue MS
Song Liao MS
Haiye Fan MS
Yu Shen MS
Zhi Nie MS
author_sort Zhengbiao Xue MS
collection DOAJ
description Background Atrial fibrillation (AF) is a leading cause of stroke, necessitating effective anticoagulation. While direct oral anticoagulants (DOACs) have improved stroke prevention, bleeding risks remain a concern. Factor XI/XIa inhibitors, targeting the intrinsic coagulation pathway, offer potential for reduced bleeding, although questions remain regarding their efficacy. This systematic review evaluates the efficacy and safety of Factor XI/XIa inhibitors compared to DOACs in AF patients. Methods We conducted a systematic review of randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients, identified through PubMed and Embase up to January 2025. Data were synthesized narratively due to heterogeneity in study designs and outcomes. Results Three RCTs (AZALEA-TIMI 71, OCEANIC-AF, PACIFIC-AF) involving 16 852 patients were included. Factor XI/XIa inhibitors (abelacimab and asundexian) demonstrated significant reductions in bleeding compared to DOACs. In AZALEA-TIMI 71, abelacimab reduced major or clinically relevant non-major bleeding by 62%-69% versus rivaroxaban. In PACIFIC-AF, asundexian reduced bleeding by 50%-84% compared to apixaban. However, OCEANIC-AF showed asundexian was inferior in stroke prevention, with a 3.8-fold higher risk of stroke or systemic embolism compared to apixaban, leading to early trial termination. Abelacimab showed a trend toward higher ischemic stroke rates abelacimab (150 mg: 1.21 vs 0.59 events/100 person-years; and 90 mg: 1.24 vs 0.59 events/100 person-years), though not statistically significant. Conclusion Factor XI/XIa inhibitors significantly reduce bleeding risk in AF patients compared to DOACs, but their thrombotic efficacy remains uncertain. While promising, further research is needed to optimize their use.
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spelling doaj-art-9613f322bb1d405d935b7b47962f77382025-08-20T01:48:24ZengSAGE PublishingClinical and Applied Thrombosis/Hemostasis1938-27232025-04-013110.1177/10760296251335967A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial FibrillationZhengbiao Xue MS0Song Liao MS1Haiye Fan MS2Yu Shen MS3Zhi Nie MS4 Department of Critical Care Medicine, , Ganzhou, Jiangxi, China Intensive Care Medicine Department, Dayu County People's Hospital, Ganzhou, Jiangxi, China The First Clinical Medical College, , Ganzhou, Jiangxi, China The First Clinical Medical College, , Ganzhou, Jiangxi, China Intensive Care Medicine Department, Dayu County People's Hospital, Ganzhou, Jiangxi, ChinaBackground Atrial fibrillation (AF) is a leading cause of stroke, necessitating effective anticoagulation. While direct oral anticoagulants (DOACs) have improved stroke prevention, bleeding risks remain a concern. Factor XI/XIa inhibitors, targeting the intrinsic coagulation pathway, offer potential for reduced bleeding, although questions remain regarding their efficacy. This systematic review evaluates the efficacy and safety of Factor XI/XIa inhibitors compared to DOACs in AF patients. Methods We conducted a systematic review of randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients, identified through PubMed and Embase up to January 2025. Data were synthesized narratively due to heterogeneity in study designs and outcomes. Results Three RCTs (AZALEA-TIMI 71, OCEANIC-AF, PACIFIC-AF) involving 16 852 patients were included. Factor XI/XIa inhibitors (abelacimab and asundexian) demonstrated significant reductions in bleeding compared to DOACs. In AZALEA-TIMI 71, abelacimab reduced major or clinically relevant non-major bleeding by 62%-69% versus rivaroxaban. In PACIFIC-AF, asundexian reduced bleeding by 50%-84% compared to apixaban. However, OCEANIC-AF showed asundexian was inferior in stroke prevention, with a 3.8-fold higher risk of stroke or systemic embolism compared to apixaban, leading to early trial termination. Abelacimab showed a trend toward higher ischemic stroke rates abelacimab (150 mg: 1.21 vs 0.59 events/100 person-years; and 90 mg: 1.24 vs 0.59 events/100 person-years), though not statistically significant. Conclusion Factor XI/XIa inhibitors significantly reduce bleeding risk in AF patients compared to DOACs, but their thrombotic efficacy remains uncertain. While promising, further research is needed to optimize their use.https://doi.org/10.1177/10760296251335967
spellingShingle Zhengbiao Xue MS
Song Liao MS
Haiye Fan MS
Yu Shen MS
Zhi Nie MS
A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation
Clinical and Applied Thrombosis/Hemostasis
title A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation
title_full A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation
title_fullStr A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation
title_full_unstemmed A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation
title_short A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation
title_sort systematic review of factor xi xia inhibitors versus direct oral anticoagulants in patients with atrial fibrillation
url https://doi.org/10.1177/10760296251335967
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