Factor XIa inhibition as a therapeutic strategy for atherothrombosis

J Thromb Thrombolysis. 2024 Dec;57(8):1297-1307. doi: 10.1007/s11239-024-03023-9. Epub 2024 Jul 29.

Abstract

When selecting an anticoagulant, clinicians consider individual patient characteristic, the treatment indication, drug pharmacology, and safety and efficacy as demonstrated in randomized trials. An ideal anticoagulant prevents thrombosis with little or no increase in bleeding. Direct oral anticoagulants represent a major advance over traditional anticoagulants (e.g., unfractionated heparin, warfarin) but still cause bleeding, particularly from the gastrointestinal tract which can limit their use. Epidemiological studies indicate that patients with congenital factor XI (FXI) deficiency have a lower risk of venous thromboembolism (VTE) and ischemic stroke (IS) than non-deficient individuals, and do not have an increased risk of spontaneous bleeding, even with severe deficiency. These observations provide the rationale for targeting FXI as a new class of anticoagulant. Multiple FXI inhibitors have been introduced and several are being evaluated in Phase III trials. In this review, we explain why drugs that target FXI may be associated with a lower risk of bleeding than currently available anticoagulants and summarize the completed and ongoing trials.

Keywords: Anticoagulation; Atherothrombosis; Factor XI; Factor XI inhibitors.

Publication types

  • Review

MeSH terms

  • Anticoagulants* / adverse effects
  • Anticoagulants* / therapeutic use
  • Atherosclerosis / drug therapy
  • Factor XI Deficiency / complications
  • Factor XI Deficiency / drug therapy
  • Factor XIa* / antagonists & inhibitors
  • Hemorrhage* / chemically induced
  • Humans
  • Ischemic Stroke / drug therapy
  • Ischemic Stroke / prevention & control
  • Thrombosis* / drug therapy
  • Thrombosis* / prevention & control
  • Venous Thromboembolism / drug therapy
  • Venous Thromboembolism / prevention & control

Substances

  • Factor XIa
  • Anticoagulants