https://orcid.org/0000-0001-6469-0870
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ABSTRACT
Introduction
Whilst the introduction of direct oral anticoagulants (DOACs) has improved the prevention of thromboembolic events, there is still a need for safer anticoagulants. This is particularly so, for specific populations of patients, such as those with an increased bleeding risk or those with severely reduced kidney function. People with Factor XI (FXI) deficiency are at reduced risk of thromboembolic events, without an increased risk of spontaneous bleeding. FXI inhibition, therefore, presents the ideal target for novel anticoagulants.
Areas covered
In this review, we provide an overview of the currently available anticoagulants and the emerging FXIa inhibitors in clinical trials. The need for availability of novel anticoagulants and the potential issues that will hinder the development and marketing of factor XIa inhibitors is also discussed.
Expert opinion
Evidence suggests that FXI inhibition presents a promising drug target for novel anticoagulation therapies. The FXIa inhibitors in development have advantages over DOACs with lower renal clearance and long half-lives. Overall, FXI inhibition presents a promising target, it is likely that the clinical use of FXIa inhibitors is on the horizon.
Abbreviation
| DOACs | = | Direct oral anticoagulants |
| FXI | = | Factor XI |
| FXII | = | Factor XII |
| APS | = | antiphospholipid syndrome |
| UFH | = | Unfractionated heparin |
| aPTT | = | activated partial thromboplastin |
| LMWH | = | Low molecular weight heparin |
| VKA | = | Vitamin K antagonist |
| VKOR | = | vitamin K epoxide reductase |
| NOACs | = | non-vitamin K antagonist oral anticoagulants |
| AF | = | atrial fibrillation |
| SC | = | subcutaneously |
| IV | = | intravenous |
| HIT | = | heparin-induced thrombocytopenia |
| INR | = | international normalized ratio |
| VTE | = | venous thromboembolism |
| MHS | = | Maccabi Healthcare Services |
| CV | = | cardiovascular |
| mAbs | = | monoclonal antibodies |
| ASOs | = | antisense oligonucleotides |
| FDA | = | Food and Drug Adminstration |
| PK | = | pharmacokinetic |
| PD | = | pharmacodynamics |
| Tmax | = | time to peak drug concentration |
| t1/2 | = | half-life |
| AUC | = | area under the curve |
| BMI | = | body mass index |
| CAR | = | cancer associated thrombosis |
| IgG | = | Immunoglobulin G |
| ROTEM | = | rotation thromboelastometry |
| A2 | = | apple 2 |
| SAD | = | single ascending dose |
| MAD | = | multiple ascending dose |
| qd | = | once a day |
| b.i.d. | = | twice a day |
| ESC | = | European Society of Cardiology Congress |
| LICA | = | ligand conjugated |
| AEs | = | adverse events |
Declaration of interest
G Lip reports being a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthem. No fees were 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.
Reviewer disclosures
A reviewer on this manuscript has disclosed that they are a consultant for several companies who are developing factor XI inhibitors and have served on several steering committees for clinical trials discussed in this review manuscript. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.