Factor XI inhibition in cardiovascular disease.

Cardiovascular disease remains the leading cause of mortality worldwide, with the World Health Organization estimating 17.9 million attributable deaths each year. Anticoagulants are commonly used to prevent and treat thromboembolism but currently available agents, including heparins, fondaparinux, vitamin K antagonists (VKAs), and direct oral anticoagulants (DOACs) possess inherent bleeding risks which may limit or preclude their use in patients at highest risk of bleeding. The development of a new class of anticoagulants that target factor XI (FXI) has been hailed as a potential solution to mitigate bleeding while providing effective anticoagulation. In this paper, we examine the rationale for the development of anticoagulants that target FXI and their potential future role. Specifically, we review the agents currently under clinical investigation, the available evidence regarding their efficacy and safety, the implications of recent trial discontinuations, and unresolved issues.