BREAKING NEWS: Wall Street Journal article puts spotlight on the potential of new anticoagulants taking fresh aim at one of cardiology’s toughest challenges.

November 17, 2023

Addressing Suboptimal Anticoagulation in Atrial Fibrillation

 

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 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

 

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

 

 

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