Factor XI inhibitors: can the efficacy and safety of VKAs and DOACs be improved?

Current available anticoagulants, represented by vitamin K antagonists (AVKs) and direct oral anticoagulants (ACODs), have demonstrated their efficacy in the prevention and treatment of venous and arterial thrombosis, but they are associated with an increase of bleeding complications. Inhibition of factor XI has emerged as a promising strategy to mitigate bleeding while preserving antithrombotic efficacy, because factor XI inhibition uncouples thrombosis from hemostasis. A variety of novel drugs, including antisense oligonucleotides, monoclonal antibodies and small molecules, have demonstrated both efficacy and safety in phase II trials, with phase III studies ongoing, which are covered in the current review.