The current landscape of treatment options for venous thromboembolism: a focus on novel oral anticoagulants

Abstract

Background:

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity, mortality, and healthcare expenditure. Anticoagulant therapy is recommended for at least 3 months in patients with acute VTE to prevent recurrence. Conventional anticoagulants are associated with inherent limitations including route of administration, required monitoring and dose adjustments, potential for food–drug and drug–drug interactions, unpredictable pharmacokinetics and pharmacodynamics, and possible severe adverse events.

Scope:

This manuscript reviews the pharmacology of the novel oral anticoagulants (NOACs), and analyzes the differences in phase 3 clinical trial designs, outcomes, and specific patient populations investigated for the treatment of acute and prevention of secondary VTE.

Methods:

A literature search was performed in PubMed using the key words dabigatran, apixaban, rivaroxaban, edoxaban, and venous thromboembolism in PubMed. The search included all years, English language, and peer-reviewed articles relating to phase 3 clinical trials, subanalyses, and meta-analyses of these NOACs for the treatment of acute VTE and secondary prevention.

Findings:

NOACs have demonstrated comparable efficacy and comparable or superior safety in large, randomized clinical trials in the treatment and prevention of VTE compared with conventional therapy. New oral anticoagulants, including the direct thrombin (dabigatran etexilate) and direct factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), have advantages over conventional agents such as oral administration at fixed doses, predictable pharmacokinetics and pharmacodynamics, minimal potential for food–drug and drug–drug interactions, and lack of required monitoring.

Conclusions:

NOACs offer additional oral anticoagulation treatment options for patients with VTE.

Keywords: :

• Deep vein thrombosis
• Direct factor Xa inhibitor
• Direct thrombin inhibitor
• New oral anticoagulants
• Pulmonary embolism
• Venous thromboembolism

Transparency

Declaration of funding

This study was funded by Daiichi Sankyo Inc.

Declaration of financial/other relationships

R.D.H. has disclosed that he has received grants/research support from Bayer Pharmaceuticals Corp, LEO Pharma Inc., and Sanofi-Aventis; been a consultant for Bayer Pharmaceuticals Corp., LEO Pharma Inc., Pfizer Inc., GlaxoSmithKline, and Wyeth Pharmaceuticals; and sat on advisory boards for Bayer Pharmaceuticals Corp., Pfizer Inc., and Sanofi-Aventis. M.G. has disclosed that she is an employee of AlphaBioCom LLC, which received payment from Daiichi Sankyo Inc. for work on this manuscript.

Acknowledgments

Medical writing and editorial support was provided by Emma A. Platt, PharmD – a contract employee with AlphaBioCom LLC at the time this manuscript was drafted – and was funded by Daiichi Sankyo Inc.