Edoxaban in venous thromboembolism and stroke prevention: an appraisal

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Abstract

Oral anticoagulation is the therapeutic cornerstone in preventing thromboembolic risk in both atrial fibrillation (AF) and venous thromboembolism (VTE). After decades of the sole therapeutic oral anticoagulation option being warfarin, the introduction of non-vitamin K antagonist oral anticoagulants has heralded a new era. Edoxaban is the latest addition to these available for clinical use. Edoxaban was as effective and safer than warfarin in preventing thromboembolic risk in AF patients. Similarly, edoxaban effectiveness and safety was evident when treating VTE patients to prevent recurrent VTE or VTE-related death. Therefore, edoxaban represents a valuable alternative in treating thromboembolic risk for AF and VTE patients.

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Most cited references 41

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Epidemiology of venous thromboembolism.

John Heit (2015)

Thrombosis can affect any venous circulation. Venous thromboembolism (VTE) includes deep-vein thrombosis of the leg or pelvis, and its complication, pulmonary embolism. VTE is a fairly common disease, particularly in older age, and is associated with reduced survival, substantial health-care costs, and a high rate of recurrence. VTE is a complex (multifactorial) disease, involving interactions between acquired or inherited predispositions to thrombosis and various risk factors. Major risk factors for incident VTE include hospitalization for surgery or acute illness, active cancer, neurological disease with leg paresis, nursing-home confinement, trauma or fracture, superficial vein thrombosis, and-in women-pregnancy and puerperium, oral contraception, and hormone therapy. Although independent risk factors for incident VTE and predictors of VTE recurrence have been identified, and effective primary and secondary prophylaxis is available, the occurrence of VTE seems to be fairly constant, or even increasing.

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Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial.

Christian Ruff, Robert Giugliano, Eugene Braunwald … (2015)

New oral anticoagulants for stroke prevention in atrial fibrillation were developed to be given in fixed doses without the need for the routine monitoring that has hindered usage and acceptance of vitamin K antagonists. A concern has emerged, however, that measurement of drug concentration or anticoagulant activity might be needed to prevent excess drug concentrations, which significantly increase bleeding risk. In the ENGAGE AF-TIMI 48 trial, higher-dose and lower-dose edoxaban were compared with warfarin in patients with atrial fibrillation. Each regimen incorporated a 50% dose reduction in patients with clinical features known to increase edoxaban drug exposure. We aim to assess whether adjustment of edoxaban dose in this trial prevented excess drug concentration and the risk of bleeding events.

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Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease.

Jeffrey Weitz, Tara Rasmussen, Colin Baigent … (2013)

Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting γ-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.

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Author and article information

Journal

Journal ID (nlm-ta): Vasc Health Risk Manag

Journal ID (iso-abbrev): Vasc Health Risk Manag

Journal ID (publisher-id): Vascular Health and Risk Management

Title: Vascular Health and Risk Management

Publisher: Dove Medical Press

ISSN (Print): 1176-6344

ISSN (Electronic): 1178-2048

Publication date Collection: 2016

Publication date (Electronic): 29 February 2016

Volume: 12

Pages: 45-51

Affiliations

[1 ]University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK

[2 ]Department of Internal Medicine and Medical Specialties, Sapienza-University of Rome, Rome, Italy

[3 ]Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

Author notes

Correspondence: Gregory YH Lip, University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Dudley Road, Birmingham, West Midlands B18 7QH, UK, Tel +44 121 507 5080, Fax +44 121 554 4083, Email g.y.h.lip@ 123456bham.ac.uk

Article

Publisher ID: vhrm-12-045

DOI: 10.2147/VHRM.S81569

PMC ID: 4778780

PubMed ID: 27013883

SO-VID: 2c1f54d7-fad1-48c3-9e8f-a6b6f6ce8c92

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The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

Edoxaban in venous thromboembolism and stroke prevention: an appraisal

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Karger: Cardiovascular System

Most cited references 41

Epidemiology of venous thromboembolism.

Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial.

Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease.

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