Accredited CME Program
MODERATOR
Marc S. Sabatine, MD, MPH
Chairman, TIMI Study Group
Lewis Dexter, MD Distinguished Chair in Cardiovascular Medicine Professor of Medicine
Harvard Medical School
Boston, Massachusetts, United States
FACULTY |
FACULTY |
Jeffrey l. Weitz, MD, FRCP(C), FACP, FCCP Professor of Medicine and Biochemistry McMaster University Hamilton, Ontario, Canada |
Christian T. Ruff, MD, MPH Associate Professor of Medicine Harvard Medical School Director of General Cardiology Brigham and Women’s Hospital Senior Investigator, TIMI Study Group Boston, Massachusetts, United States |
Slide presentation: Addressing Suboptimal Anticoagulation in Atrial Fibrillation SLIDE
Atrial Fibrilliation and Stroke Risk Are Underestimated
The Evolution of Anti Coagulants
Stroke Prevention in AF
DOACs vs Warfrain
DOACs Are Activated in the Gut
2019 AHA/ACC/HRS Recommendations on Anticoagulation Selection
Underuse and Inappropriate Use of DOACs for Stroke Prevention in AF
Fear of Bleeding Is a Major Driver of Undertreatment With Anticoagulation Faculty Insights
Targetting FXI
Uncoupling Thrombosis From Hemostasis
Comparison of Anticoagulant Properties
Evidence Supporting Factor XI as a Target
Emerging Factor XI/XIa Inhibitors
Mechanism of Action and Pharmacokinetics
Factor XIa vs XI Inhibition
Expert Perspectives
Meta-Analysis of Phase 2 Studies Comparing Factor XI/XIa Inhibitors vs Enoxaparin in Total Knee Replacement Recipients
Factor Xa Inhibitors in VTE
Systematic Meta-Analysis
PACIFIC Phase 2 Clinical Trial Program
Evaluating Safety of Asundexian
Pacific AF
Atrial Fibrillation1
- 20mg asundexian
- 50mg asundexian
- apixaban
755 Patients randomized
Asundexian at doses of 20mg and 50mg once daily resulted in:
- Lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with AF
PACIFIC Phase 2 Clinical Trial Program (cont)
Pacific AFAtrial Fibrillation1
755 Patients randomizedAsundexian at doses of 20mg and 50mg once daily resulted in:
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Could FXI/FXIa inhibition have a role in secondary prevention of non cardioembolic stroke and MI, where antiplatelet therapy has typically been the cornerstone treatment
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PACIFIC Phase 2 Clinical Trial Program (cont)
Phase 2 Studies in Stroke
Small-Molecule FXIa Inhibitors
PACIFIC Phase 2 Clinical Trial Program (cont)
Efficacy of Factor XI Inhibitions Post-ACS
AZALEA TIMI 71 Trial Design
Evaluating Safety of Abelacimab
AZALEA TIMI 71
Factor XI Inhibition (%) with Abelacimab
AZALEA TIMI 71
Primary Endpoint: Safety
AZALEA TIMI 71
Bleeding Endpoints and Adverse Events
Phase 3 Clinical Trials With FXI/FXIa Inhibitors
Summary of Phase 2 Trials in FXI/FXIa Inhibitors
Conclusion
- Stroke remains a leading cause of death in the United States
- DOACs are guideline-recommended over vitamin K antagonists for their ability to provide safer and more reliable prevention of thrombotic events in patients with AF; however, bleeding remains an important limitation
- There is growing enthusiasm in upstream inhibition of the coagulation cascade, targeting FXl/FXla, thereby uncoupling the intrinsic and extrinsic pathways
- In genetic and phase 2 studies, FXl/FXla have emerged as safe and potent targets for inhibition, however phase 3 studies are needed to further elucidate on the efficacy as well as long-term safety of FXl/FXla inhibitors