Weekly Journal Scan: Uncoupling thrombosis from hemostasis in atrial fibrillation? An AZALEA surfing over troubled water

This comment refers to ‘Abelacimab vs. Rivaroxaban in Patients with Atrial Fibrillation’, which was published in the New England Journal of Medicine, https://doi.org/10.1056/NEJMoa2406674. The development of a new class of anticoagulant drugs targeting the intrinsic coagulation pathway has been proposed as a strategy to dissociate thrombosis from hemostasis, potentially improving safety.2 Known as FXI inhibitors, this class includes various molecules with distinct mechanisms of action and routes of administration.3 Currently, the two most successful strategies for targeting FXI involve direct FXI inhibition and mRNA modulation, delivered via oral, subcutaneous (SC), or intravenous (IV) administration. Direct FXI inhibition is achieved through monoclonal antibodies or synthetic small molecules, while mRNA modulation utilizes antisense oligonucleotides to suppress FXI expression.3 Abelacimab is a fully humanized monoclonal antibody that binds both the inactive and active forms of Factor XI (FXI).4 Key features of abelacimab include minimal drug–drug interactions, rapid and sustained FXI inhibition enabling once-monthly SC or IV administration, and no requirement for dose adjustment based on age, renal function, or hepatic status. The AZALEA-TIMI 71 trial provides evidence for the relatively long-term safety of abelacimab 150 and 90 mg in atrial fibrillation (AF) patients. Although the trial was terminated early due to lower-than-expected bleeding with abelacimab, it reached its pre-determined sample size of 1200 patients with a planned 27-month follow-up period.