Factor XI and XIa Inhibitors: A State-of-the-Art Review Across Clinical Indications.
4 affiliations
- 1Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA.
- 2Department of Medicine, Anticoagulation and Clinical Thrombosis Services, Northwell Health at Lenox Hill Hospital, New York, NY 10075, USA.
- 3Donald and Barbara Zucker School of Medicine at Hofstra, Northwell, Hempstead, NY 11549, USA.
- 4Elmezzi Graduate School of Molecular Medicine, Manhasset, NY 11030, USA.
Abstract
Balancing thrombotic and bleeding risk remains the central challenge of anticoagulation, and clinically significant bleeding continues to limit even direct oral anticoagulants, especially in high-bleeding-risk patients. Factor XI (FXI) and activated FXI (FXIa) inhibitors are a mechanistically novel class that seeks to uncouple thrombosis from hemostasis; FXI amplifies clot formation through the intrinsic pathway but contributes little to physiologic hemostasis. This state-of-the-art review examines three classes of FXI/FXIa inhibitors (antisense oligonucleotides, monoclonal antibodies, and small-molecule inhibitors) that are in advanced phase II and III clinical trials, and synthesizes currently available evidence across six indications, including primary thromboprophylaxis in high-bleed-risk orthopedic surgery, primary thromboprophylaxis in end-stage renal disease, stroke prevention in atrial fibrillation, acute coronary syndromes, secondary stroke prevention, and treatment of cancer-associated venous thromboembolism. A pattern emerges, where FXI/FXIa inhibition offers a favorable safety profile across multiple settings and high-risk subgroups, yet clear efficacy has so far been established only in secondary prevention of noncardioembolic ischemic stroke over existing antiplatelet strategies. Although unlikely to completely replace current anticoagulants, these agents may offer important therapeutic options for selected high-risk populations. Ongoing phase II and III trials will further define their potential advantages in areas of unmet clinical need.
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BibTeX
@article{oikonomou2026factor,
title = {{Factor XI and XIa Inhibitors: A State-of-the-Art Review Across Clinical Indications.}},
author = {Ermioni Oikonomou and Mark Goldin and Alex C Spyropoulos},
journal = {Journal of clinical medicine},
year = {2026},
month = sep,
doi = {10.3390/jcm15197431},
url = {https://europepmc.org/article/MED/42881892},
note = {CC BY},
}
RIS
TY - JOUR
TI - Factor XI and XIa Inhibitors: A State-of-the-Art Review Across Clinical Indications.
AU - Ermioni Oikonomou
AU - Mark Goldin
AU - Alex C Spyropoulos
PY - 2026
DA - 2026/09/24
JO - Journal of clinical medicine
DO - 10.3390/jcm15197431
UR - https://europepmc.org/article/MED/42881892
AB - Balancing thrombotic and bleeding risk remains the central challenge of anticoagulation, and clinically significant bleeding continues to limit even direct oral anticoagulants, especially in high-bleeding-risk patients. Factor XI (FXI) and activated FXI (FXIa) inhibitors are a mechanistically novel class that seeks to uncouple thrombosis from hemostasis; FXI amplifies clot formation through the intrinsic pathway but contributes little to physiologic hemostasis. This state-of-the-art review examines three classes of FXI/FXIa inhibitors (antisense oligonucleotides, monoclonal antibodies, and small-molecule inhibitors) that are in advanced phase II and III clinical trials, and synthesizes currently available evidence across six indications, including primary thromboprophylaxis in high-bleed-risk orthopedic surgery, primary thromboprophylaxis in end-stage renal disease, stroke prevention in atrial fibrillation, acute coronary syndromes, secondary stroke prevention, and treatment of cancer-associated venous thromboembolism. A pattern emerges, where FXI/FXIa inhibition offers a favorable safety profile across multiple settings and high-risk subgroups, yet clear efficacy has so far been established only in secondary prevention of noncardioembolic ischemic stroke over existing antiplatelet strategies. Although unlikely to completely replace current anticoagulants, these agents may offer important therapeutic options for selected high-risk populations. Ongoing phase II and III trials will further define their potential advantages in areas of unmet clinical need.
SN - 2077-0383
ER -