Journal Club - Less Bleeding With Factor XI Inhibitor finds PACIFIC AF trial

An enormous amount of developments have taken place in the development of safe and effective anticoagulants and a number of anticoagulants including rivoroxiban and debigratin and others have been developed to benefit the patients of high thrombotic risk. An on going research is now trying factor 11a inhibitor for better safety and efficacy.    

A new antithrombotic agent in development that targets a novel pathway — inhibition of activated coagulation factor XI — might be able to reduce thromboembolic events with a lower risk of bleeding than currently available anticoagulants, new data suggest. Results from the PACIFIC-AF phase 2 study of asundexian, a small-molecule oral inhibitor of activated factor XI, in patients with atrial fibrillation (AF) showed the drug to be well tolerated and associated with significantly lower bleeding rates than apixaban. Researchers presented the results of the PACIFIC-AF trial on April 3 at the American College of Cardiology (ACC) 2022 Scientific Session. The study was simultaneously published online in the Lancet.

In the Lancet publication, the researchers noted that current guidelines recommend non-vitamin K antagonists — also called novel oral anticoagulants (NOACs) or direct oral anticoagulants (DOACs), which mainly inhibit factor X — for stroke prevention in patients with AF because of their improved safety and efficacy over vitamin K antagonists. But use of these agents is still limited because of concerns around bleeding, particularly in vulnerable or older patients with renal dysfunction.

They report that data have identified inhibition of activated factor XI as a new target to prevent thrombosis with minimal effect on hemostasis and bleeding. Activated factor XI is thought to contribute to clot progression, which can lead to vessel occlusion and pathologic manifestations of thrombosis, but, in contrast to other clotting factors, activated factor XI has only a minor effect on clot consolidation during hemostasis.

Hence, factor XI inhibition is a promising strategy to prevent pathologic thrombi while minimizing bleeding risk in AF patients.