Factor XI Inhibitors for Stroke Prevention

This episode, titled “Factor XI Inhibitors for Stroke Prevention,” features Ashkan Shoamanesh, MD, FRCPC, FESO Eva Mistry, MD, Greg Albers, MD, and James Siegler, MD discussing the following topics:

1. Discuss the rationale behind increased interest in Factor XIa for secondary stroke prevention.
   1. How important is separation between thrombosis and bleeding control in short and long-term stroke management?
2. Briefly discuss the various Factor XIa targeting agents that are currently under investigation and phase 2 studies with asundexian (PACIFIC-STROKE) and milvexian (AXIOMATIC-SSP).

Factor XI inhibition is presented as a major future advance in stroke prevention because it may provide strong antithrombotic benefit without adding bleeding risk, unlike current anticoagulants and antiplatelet combinations. Interest in factor XI began with patients who have factor XI deficiency, who show fewer ischemic strokes and venous thromboembolic events but do not exhibit a major bleeding tendency, a finding later confirmed in animal studies. This led to development of multiple factor XI–targeting strategies (antisense oligonucleotides, monoclonal antibodies, and especially small-molecule direct factor XIa inhibitors such as asundexian and milvexian) for secondary stroke prevention. Phase 2 trials (AXIOMATIC-SSP and PACIFIC-STROKE) in noncardioembolic stroke and high-risk TIA showed neutral primary composite outcomes but signaled dose-dependent reductions in clinical ischemic stroke and in the composite of stroke or TIA, supporting progression to large phase 3 programs (OCEANIC-STROKE and LIBREXIA-STR

In the next episode, “Mechanism of Action of Factor XI Inhibitors,” panelists will continue their discussion on why factor XI inhibitors are an attractive target for stroke prevention.