Factor XI inhibition fulfilling the optimal expectations for ideal anticoagulation

ABSTRACT

Introduction: Thromboembolic diseases are leading cause of mortality accounting for an estimated 1 in 4 deaths all over the world. Anticoagulation remains the mainstay of prevention and treatment of venous thromboembolic disorders. Conventional anticoagulants have been efficiently used over the last decades, but their clinical use encounters safety and convenience issues. To overcome these limitations, research have focused on development of new targets for anticoagulation leading to a relatively new class of drugs, non-vitamin K antagonist oral anticoagulants, specifically targeting activated factor X and thrombin. However, the search for more potent anticoagulant agents with reduced bleeding risk is still continuing.

Areas covered: In this review, we provide an overview on emerging investigational anticoagulant drugs targeting factor XI in the coagulation cascade. We review data about the role of intrinsic pathway in thrombosis and haemostasis and the rationale of different pharmacodynamic approaches targeting factor XI.

Expert opinion: Recent evidence suggests that the contact pathway plays a significant role in thrombosis by thrombus stabilization and growth without perturbing haemostasis. Factor XI might be a promising drug target to develop highly effective antithrombotic therapy with safety bleeding profile. Most of these investigational agents are in early development phases, only few have reached early phase clinical trials.

KEYWORDS:

• Anticoagulation
• coagulation cascade
• drug discovery
• factor XI
• haemostasis
• investigational drugs
• intrinsic pathway
• novel anticoagulants
• thrombosis

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

GYH Lip is a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo. He is a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are directly received personally. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.