Address of Corresponding Author

Pathophysiol Haemos Thromb 2005;34 (Suppl. 1):18-24 (DOI: 10.1159/000083080)

  Key Words

• Ximelagatran
• Oral direct thrombin inhibitors
• VTE treatment and secondary prevention
• New anticoagulants
• THRIVE trials
• Oral vitamin K antagonists

  Abstract

Clinical-based evidence demonstrates that long-term oral anticoagulant therapy with the vitamin K antagonists is highly effective for the secondary prevention of venous thromboembolism (VTE). However, owing to fear of bleeding complications and the inconvenience of coagulation monitoring, many patients do not receive the required duration of treatment. This can lead to a high incidence of recurrent VTE events and has prompted the evaluation of alternative treatment strategies and the development of new anticoagulants for VTE management. For patient groups in which it is particularly difficult to maintain the target intensity of anticoagulation, low-molecular-weight heparin (LMWH) has been found to significantly reduce the risk of recurrent VTE without increasing bleeding risk. The parenteral administration of LMWH, however, is a drawback for long-term use in the outpatient setting. Long-term warfarin use at a lower intensity (international normalized ratio [INR] 1.5-2.0) has also been assessed as a possible strategy to reduce bleeding complications and the need for monitoring, but results were disappointing when compared with conventional-intensity warfarin (INR 2.0-3.0). New therapies in development that may potentially offer a more favourable benefit-risk profile and greater consistency and predictability of response include the synthetic pentasaccharides, fondaparinux and idraparinux. These par enterally administered indirect factor Xa inhibitors have a predictable pharmacokinetic profile, allowing use without coagulation monitoring. Fondaparinux to date has only been evaluated in the initial treatment (5-7 days) of symptomatic deep vein thrombosis. In contrast, idraparinux, with its longer half-life (80 h) allowing once-weekly parenteral dosing, has the potential for long-term treatment and is currently being assessed in phase III trials for the secondary prevention of VTE. Currently, the most promising new therapeutic option is the first of the oral direct thrombin inhibitors, ximelagatran. The THRombin Inhibitor in VEnous thromboembolism (THRIVE) clinical trial programme has demonstrated that this agent is as effective as standard therapy for the acute treatment (THRIVE Treatment) and secondary prevention (THRIVE lll) of VTE events and is well tolerated when used for 6 months or over extended periods up to 1.5 years. Furthermore, with oral administration, fixed dosing and no requirement for anticoagulation monitoring, ximelagatran has the potential to facilitate optimal use and duration of VTE treatment by overcoming the limitations of current agents.

Copyright © 2005 S. Karger AG, Basel

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  Author Contacts

Dr. Sam Schulman
HHS - General Hospital
237 Barton St. East
Hamilton, Ont. L8L 2X2 (Canada)
Tel. +1 905 528 9946, Fax +1 905 521 1551, E-Mail schulms@mcmaster.ca

  Article Information

Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 0, Number of References : 20

  Publication Details

Pathophysiology of Haemostasis and Thrombosis

Vol. 34, No. Suppl. 1, Year 2005 (Cover Date: February 2005)

Journal Editor: Rosing, J. (Maastricht)
ISSN: 1424-8832 (print), 1424-8840 (Online)

For additional information: http://www.karger.com/pht

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