Perspectives: what we are learning from factor XI/factor XIa inhibitor trials.
10 affiliations
- 1Department of Medical Education, The France Foundation, Old Lyme, Connecticut, USA.
- 2Department of Medicine and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
- 3National Heart and Lung Institute, Imperial College Healthcare NHS, London, UK.
- 4Department INECO Neurociencias, World Stroke Organization Heart and Brain Task Force, Rosario, Argentina.
- 5Department of Neurology, Amsterdam University Medical Center, Amsterdam, the Netherlands.
- 6Department of Neurology, University of California, San Francisco, California, USA.
- 7Division of Hematology Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- 8Department of Cardiology and Director of Women's Heart Health, National Heart Centre Singapore, Duke-National University, Singapore, Singapore.
- 9Division of Hematology, University of Ottawa, the Ottawa Hospital, Ottawa, Ontario, Canada.
- 10Selzman Institute for Kidney Health, Baylor College of Medicine, Houston, Texas, USA.
Abstract
Over the past decade, a diverse pipeline of factor XI (FXI)/XIa-targeting agents has entered clinical development, including oral small-molecule inhibitors, monoclonal antibodies, antisense oligonucleotides, and small interfering RNAs. Across early- and late-phase clinical trials, these agents have generally shown a favorable safety profile, with consistently low rates of major bleeding, even when used with antiplatelet therapy or compared with standard anticoagulants. However, efficacy signals have varied by clinical setting. In venous thromboembolism prophylaxis after orthopedic surgery and in secondary stroke prevention, FXI/XIa inhibition has shown encouraging antithrombotic activity. In contrast, trials in atrial fibrillation, acute coronary syndrome, and cancer-associated thrombosis have yielded mixed efficacy results, highlighting potential limitations of intrinsic pathway inhibition in conditions with high thrombin generation or platelet-driven thrombosis. Collectively, these findings position FXI/XIa inhibitors as a potential paradigm shift in antithrombotic therapy for targeted indications, with ongoing phase 3 studies expected to further define their clinical role and optimal use across diverse thrombotic disorders.
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BibTeX
@article{glasner2026perspectives,
title = {{Perspectives: what we are learning from factor XI/factor XIa inhibitor trials.}},
author = {Melissa F Glasner and Jeffrey I Weitz and Rasha Al-Lamee and María Cecilia Bahit and Jonathan M Coutinho and S Claiborne Johnston and David Gailani and Carolyn S P Lam and Tzu-Fei Wang and Wolfgang C Winkelmayer},
journal = {Research and practice in thrombosis and haemostasis},
year = {2026},
month = aug,
doi = {10.1016/j.rpth.2026.106936},
url = {https://europepmc.org/article/MED/42936046},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Perspectives: what we are learning from factor XI/factor XIa inhibitor trials.
AU - Melissa F Glasner
AU - Jeffrey I Weitz
AU - Rasha Al-Lamee
AU - María Cecilia Bahit
AU - Jonathan M Coutinho
AU - S Claiborne Johnston
AU - David Gailani
AU - Carolyn S P Lam
AU - Tzu-Fei Wang
AU - Wolfgang C Winkelmayer
PY - 2026
DA - 2026/08/29
JO - Research and practice in thrombosis and haemostasis
DO - 10.1016/j.rpth.2026.106936
UR - https://europepmc.org/article/MED/42936046
AB - Over the past decade, a diverse pipeline of factor XI (FXI)/XIa-targeting agents has entered clinical development, including oral small-molecule inhibitors, monoclonal antibodies, antisense oligonucleotides, and small interfering RNAs. Across early- and late-phase clinical trials, these agents have generally shown a favorable safety profile, with consistently low rates of major bleeding, even when used with antiplatelet therapy or compared with standard anticoagulants. However, efficacy signals have varied by clinical setting. In venous thromboembolism prophylaxis after orthopedic surgery and in secondary stroke prevention, FXI/XIa inhibition has shown encouraging antithrombotic activity. In contrast, trials in atrial fibrillation, acute coronary syndrome, and cancer-associated thrombosis have yielded mixed efficacy results, highlighting potential limitations of intrinsic pathway inhibition in conditions with high thrombin generation or platelet-driven thrombosis. Collectively, these findings position FXI/XIa inhibitors as a potential paradigm shift in antithrombotic therapy for targeted indications, with ongoing phase 3 studies expected to further define their clinical role and optimal use across diverse thrombotic disorders.
SN - 2475-0379
ER -