Factor XI inhibitors in adjunct to antiplatelet therapy: the ultimate dual-pathway inhibition?

A strategy of oral anticoagulants (OAC) in addition to single or dual antiplatelet therapy, known as dual-pathway inhibition (DPI), has shown to reduce thrombotic events in patients with cardiovascular disease. However, despite its efficacy, its use in clinical practice has been hindered by the fact this strategy is also associated with increased bleeding, including major bleeding. The use of low dose direct oral anticoagulant (i.e. rivaroxaban 2.5 mg twice daily) on top of antiplatelet therapy has been associated with reduced bleeding, but some safety concerns still exists. The availability of a novel class of OACs selectively targeting the intrinsic coagulation pathway and potentially uncoupling thrombosis and hemostasis has sparked the interest towards the use of a new generation DPI strategy associated with enhanced safety. Several phase II trials using factor XI (FXI) inhibitors on top of antiplatelet therapy in patients with coronary artery or cerebrovascular disease have been recently published and others are under investigation. We here discuss the available evidence and future perspectives of DPI with FXI inhibitors in patients with cardiovascular disease.