Factor XI(a) Inhibition in Secondary Stroke Prevention: On the Cusp of a New Anticoagulation Paradigm.
- 1Division of Basic and Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125, United States.
Abstract
Ischemic stroke remains a leading contributor to global mortality and long-term disability, while bleeding complications, particularly intracranial hemorrhage, continue to constrain the use of conventional antithrombotic therapies for secondary prevention. Factor XI (FXI) has emerged as an attractive therapeutic target because it promotes thrombin amplification and pathological thrombus stabilization while contributing only modestly to physiological hemostasis, forming the basis for "hemostasis-sparing" anticoagulation. Current FXI-targeted approaches include oral small-molecule FXIa inhibitors (asundexian and milvexian), antisense oligonucleotides (fesomersen), and monoclonal antibodies (abelacimab and osocimab). Among these, oral FXIa inhibitors appear particularly suited for long-term cerebrovascular prevention because they provide rapid, reversible target inhibition. Phase II trials, including PACIFIC-Stroke and AXIOMATIC-SSP, showed neutral primary efficacy end points but consistently favorable safety outcomes. More recently, the phase III OCEANIC-STROKE trial demonstrated that asundexian 50 mg once daily added to antiplatelet therapy reduced recurrent ischemic stroke by 26% (HR 0.74; 95% CI 0.65-0.84) without a significant increase in major bleeding among patients with noncardioembolic stroke. In contrast, OCEANIC-AF showed inferior efficacy compared with apixaban in atrial fibrillation, suggesting that the therapeutic value of FXIa inhibition is strongly dependent on clinical context. Taken together, this review summarizes the pathophysiological rationale, pharmacology, and clinical evidence supporting FXI inhibition for secondary ischemic stroke prevention and discusses future precision-medicine strategies for patient selection.
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BibTeX
@article{alhorani2026factor,
title = {{Factor XI(a) Inhibition in Secondary Stroke Prevention: On the Cusp of a New Anticoagulation Paradigm.}},
author = {Rami A Al-Horani},
journal = {ACS pharmacology \& translational science},
year = {2026},
month = sep,
doi = {10.1021/acsptsci.6c00298},
url = {https://europepmc.org/article/MED/42847068},
note = {CC BY},
}
RIS
TY - JOUR
TI - Factor XI(a) Inhibition in Secondary Stroke Prevention: On the Cusp of a New Anticoagulation Paradigm.
AU - Rami A Al-Horani
PY - 2026
DA - 2026/09/11
JO - ACS pharmacology & translational science
DO - 10.1021/acsptsci.6c00298
UR - https://europepmc.org/article/MED/42847068
AB - Ischemic stroke remains a leading contributor to global mortality and long-term disability, while bleeding complications, particularly intracranial hemorrhage, continue to constrain the use of conventional antithrombotic therapies for secondary prevention. Factor XI (FXI) has emerged as an attractive therapeutic target because it promotes thrombin amplification and pathological thrombus stabilization while contributing only modestly to physiological hemostasis, forming the basis for "hemostasis-sparing" anticoagulation. Current FXI-targeted approaches include oral small-molecule FXIa inhibitors (asundexian and milvexian), antisense oligonucleotides (fesomersen), and monoclonal antibodies (abelacimab and osocimab). Among these, oral FXIa inhibitors appear particularly suited for long-term cerebrovascular prevention because they provide rapid, reversible target inhibition. Phase II trials, including PACIFIC-Stroke and AXIOMATIC-SSP, showed neutral primary efficacy end points but consistently favorable safety outcomes. More recently, the phase III OCEANIC-STROKE trial demonstrated that asundexian 50 mg once daily added to antiplatelet therapy reduced recurrent ischemic stroke by 26% (HR 0.74; 95% CI 0.65-0.84) without a significant increase in major bleeding among patients with noncardioembolic stroke. In contrast, OCEANIC-AF showed inferior efficacy compared with apixaban in atrial fibrillation, suggesting that the therapeutic value of FXIa inhibition is strongly dependent on clinical context. Taken together, this review summarizes the pathophysiological rationale, pharmacology, and clinical evidence supporting FXI inhibition for secondary ischemic stroke prevention and discusses future precision-medicine strategies for patient selection.
SN - 2575-9108
ER -