Key result
Emerging factor XI/XIa and glycoprotein VI inhibitors show promise in preventing thrombosis without increasing bleeding.
Why the study?
Current antithrombotic agents carry bleeding risks that limit their use, especially in patients with cancer-associated venous thromboembolism, high bleeding risk atrial fibrillation, and end-stage renal disease, and new agents are needed to improve the risk-benefit profile.
Factor XI/XIa and glycoprotein VI inhibitors represent promising emerging antithrombotic classes that may decouple thrombosis from hemostasis, potentially reducing bleeding risks in vulnerable populations.
Supports apixaban as oral alternative to LMWH for cancer-associated VTE; extends RCT evidence for DOACs in high-bleeding-risk patients.
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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Geoffrey D. Barnes (2024) conducted a review in Arterial and venous thromboses. Factor XI/XIa inhibitors and glycoprotein VI inhibitors was evaluated. Emerging antithrombotic agents, including factor XI/XIa inhibitors and glycoprotein VI inhibitors, show promise in preventing pathologic thrombosis without increasing hemostatic-related bleeding risk.
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