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Updated: Jun 5, 2025
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
New targets for antithrombotic medications: seeking to decouple thrombosis from hemostasis
1Division of Cardiovascular Medicine, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA.
Insights
New antithrombotic agents targeting Factor XI/XIa and glycoprotein VI show promise for preventing dangerous blood clots without increasing bleeding risk. Ongoing studies aim to confirm their safety and efficacy in high-risk patients.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Pharmacology
Background:
- Arterial and venous thromboses are leading global causes of death.
- Current antithrombotic therapies carry a significant bleeding risk, limiting their use in specific patient populations.
- Existing treatments offer suboptimal risk-benefit profiles for patients with cancer-associated venous thromboembolism, atrial fibrillation, end-stage renal disease, ischemic stroke, and acute coronary syndromes.
Purpose of the Study:
- To review emerging antithrombotic agents, specifically factor (F)XI/XIa inhibitors and glycoprotein VI inhibitors.
- To evaluate their potential to prevent pathological thrombosis with a reduced risk of bleeding complications.
- To discuss their ongoing investigation in phase 3 clinical trials for various thrombotic conditions.
Main Methods:
- Review of phase 2 study data for novel antithrombotic agents.
- Focus on factor (F)XI/XIa inhibitors (abelacimab, asundexian, milvexian) and glycoprotein VI inhibitors (glenzocimab).
- Analysis of ongoing phase 3 clinical trials in patient cohorts including atrial fibrillation, cancer-associated venous thromboembolism, acute coronary syndrome, and ischemic stroke.
Main Results:
- Phase 2 studies indicate that FXI/FXIa inhibitors and glycoprotein VI inhibitors may prevent thrombosis without a significant increase in bleeding risk.
- Several agents are in advanced clinical development across diverse thrombotic conditions.
- These emerging therapies aim to address unmet needs where current treatments are limited by safety concerns.
Conclusions:
- Factor (F)XI/XIa and glycoprotein VI inhibitors represent promising new classes of antithrombotic agents.
- If phase 3 trials confirm efficacy and safety, these agents could significantly improve outcomes for patients with challenging thrombotic conditions.
- These novel therapies have the potential to offer a more favorable risk-benefit profile compared to existing treatments.
Abstract:
Arterial and venous thromboses are the leading causes of morbidity and mortality worldwide. Numerous antithrombotic agents are currently available with antiplatelet, thrombolytic/fibrinolytic, and anticoagulant activity. However, all the currently available antithrombotic agents carry a risk of bleeding that often prevents their use. This unfavorable risk-benefit profile is particularly challenging for patients with cancer-associated venous thromboembolism, patients with atrial fibrillation at a high risk of bleeding, and patients with end-stage renal disease. Patients with ischemic stroke and acute coronary syndromes have not yet found a favorable risk-benefit profile with anticoagulant therapy to help reduce the residual thromboembolic risk that remains after antiplatelet and lipid therapy. Two emerging classes of antithrombotic agents, factor (F)XI or activated factor Ⅺ (FⅪa) inhibitors and glycoprotein VI inhibitors, have shown promise in their ability to prevent pathologic thrombosis without increasing the risk of hemostatic-related bleeding in phase 2 studies. Among the FⅪ/FXIa inhibitors of coagulation, a parenterally administered monoclonal antibody (abelacimab) and 2 orally administered small molecule inhibitors (asundexian, milvexian) are collectively being studied in patients with atrial fibrillation, cancer-associated venous thromboembolism, acute coronary syndrome, and ischemic stroke. One parenterally administered glycoprotein VI antiplatelet agent (glenzocimab) is currently being studied in patients with ischemic stroke. If shown to be efficacious and safe in ongoing phase 3 studies, both classes of emerging antithrombotic agents have the potential to greatly improve outcomes for patients with challenging thrombotic conditions.
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