Current and emerging drug strategies for the prevention of venous thromboembolism in acutely ill medical inpatients

ABSTRACT

Introduction

Venous thromboembolism (VTE) is a common complication in patients hospitalized for acute medical illnesses. Therefore, medical inpatients require a careful VTE and bleeding risk assessment to drive optimal strategies for VTE prevention. Low molecular weight heparin and fondaparinux have long been used for inhospital prophylaxis for patients at increased risk of VTE. The selection of patients who require post-discharge prophylaxis, and the role of direct oral anticoagulants remain debated. New molecules currently under development may contribute to improve the risk benefit of VTE prevention in this setting.

Areas covered

This text summarizes the evidence on approved treatments and on other drugs for the prevention of VTE in acutely ill medical patients. The main focus is on their pharmacological properties, clinical efficacy and safety, and the current license approved by the FDA (Food and Drug Administration) and EMA (European Medicines Agency). The trials presented consider both inhospital and extended prophylaxis.

Expert opinion

Thanks to the potentially favorable safety profile, factor XI inhibitors may play a role in the prevention of VTE in this setting. The expert opinion section discusses pharmacological properties, prophylaxis trials, and potential clinical applications of this novel class of drugs.

KEYWORDS:

• VTE
• enoxaparin
• fondaparinux
• rivaroxaban
• apixaban
• betrixaban
• thromboprophylaxis
• DOAC
• factor XI inhibitors
• LMWH
• direct oral anticoagulants

Article highlights

• To date, unfractionated heparin, low molecular-weight heparin, fondaparinux, and rivaroxaban are the available options for thromboprophylaxis in acute medical inpatients.

• The hemorrhagic burden is one of the main issues in this setting. A careful analysis of the hemorrhagic risk, together with the thrombotic risk, should be done in all patients before administering the antithrombotic drug.

• Introducing new criteria to select low bleeding risk and high venous thromboembolism (VTE) recurrence risk patients could be an option to select a population that could benefit more from antithrombotic drugs. However, there is still need for prospective validations.

• To date, antithrombotic prophylaxis in the acute medical patient, according to the guidelines, is only recommended until hospital discharge. Due to the low number of clinically relevant thrombotic events and increased bleeding risk, extended prophylaxis is not recommended.

• Factor XI inhibitors could become the class of anticoagulant drugs with low bleeding risk, which could represent a solution for patients at high risk of VTE after hospital discharge. However, to date no randomized trial has been carried out in acutely ill medical inpatients.

Declaration of interests

W Ageno is on the advisory boards for Bayer, Leo Pharma, Sanofi, Norgine and Viatris. A Squizzato has conducted paid lectures for Bayer, Pfizer, Novartis, Roche, Daiichi Sankyo, Werfen, and Alexion and is on the advisory boards for Bayer, Viatris, 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.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.