New anticoagulants for venous thromboembolism and atrial fibrillation: what the future holds

ABSTRACT

Introduction: The field of anticoagulation has seen impressive progress over the last decade. The introduction of the Non Vitamin K Oral Anticoagulants (NOACs) has revolutionized practice surrounding thromboprophylaxis, treatment of thromboembolic disease and stroke prevention in atrial fibrillation (AF). However, the search for the ‘holy grail’ of anticoagulation, an agent that combines optimal efficacy with minimal bleeding diathesis, continues.

Areas covered: In this paper we aim to summarize the current evidence from pre-clinical studies and early phase clinical trials, presenting the pharmacodynamic and pharmacokinetic properties as well as the safety and efficacy profiles of the most important antithrombotic agents in development.

Expert opinion: Research focused on the development of new anticoagulation agents is rapidly expanding. Although the exploration of antithrombotic agents that act on well-established targets such factor Xa and thrombin remains the mainstay, attention has also shifted to other factors in the coagulation cascade. The evidence emerging from clinical research is growing, generating exciting possibilities in the field of anticoagulation.

KEYWORDS:

• Anticoagulation
• atrial fibrillation
• stroke
• thromboprophylaxis
• thromboembolism
• anticoagulation reversal

Article highlights

• Non Vitamin K Oral Anticoagulants have become the mainstay of treatment for the prevention of stroke prophylaxis in atrial fibrillation and the prophylaxis and treatment of venous thromboembolism. Research on the development of new anticoagulant agents is growing rapidly

• Betrixaban is a novel oral direct factor Xa inhibitor that became recently the first NOAC licensed for thromboprophylaxis in acute medically ill patients

• Antisense Oligonucleotides inhibiting factor XI have been successfully tested for the prevention of thromboembolism in patients undergoing orthopaedic surgery

• Monoclonal antibodies targeting factors XI and XII have demonstrated thromboprophylactic effects in animal models

• Tecarfarin is a new vitamin K antagonist under development that is not metabolised by the cytochrome 450 system. It has demonstrated similar anticoagulant effects compared to warfarin with fewer interactions in patients on concomitant CYP2C9 medications

• Idarucizumab, Andexanet alfa and Ciraparantag are the key anticoagulation reversal agents in the pipeline

This box summarizes key points contained in the article.

Declaration of interest

G. Y. H. Lip has served as a consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife and Daiichi-Sankyo. Speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo. 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. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.