1887
Volume 2005, Issue 2
  • ISSN: 0253-8253
  • EISSN: 2227-0426

Abstract

This article presents the available data on Ximelagatran, a novel oral direct thrombin inhibitor and explores its therapeutic potential Recent large clinical trials have evaluated the efficacy and safety of this anticoagulant compared to the standard anticoagulation therapy with warfarin and heparins in several thrombotic disorders. These trials provide strong evidence for the efficacy and safety of ximelagatran in the following clinical indications; the prevention of venous thromboembolism after knee or hip replacement, the treatment of deep venous thrombosis, and prevention of stroke in patients with atrial fibrillation. Further evaluation of this promising oral anticoagulant is warranted in other thrombotic cardiovascular disorders requiring chronic oral anticoagulation therapy such as in patients with prosthetic heart valves, intracardiac thrombi, dilated cardiomyopathy, after myocardial infarction and post percutaneous coronary interventions.

Loading

Article metrics loading...

/content/journals/10.5339/qmj.2005.2.8
2005-11-01
2024-03-28
Loading full text...

Full text loading...

References

  1. Gustafsson D, Elg M:. The pharmacodynamics and pharmacokinetics of the oral direct thrombin inhibitor ximelagatran and its active metabolite melagatran: A mini-review. Thromb Res. 2003; 109:Suppl 1:S915.
    [Google Scholar]
  2. Salam AM, Al Mousa EN. The therapeutic potential of ximelagatran to become the anticoagulant of choice in medicine: A review of recently completed clinical trials. Expert Opin Pharmacother. 2004; 5:6:14231430.
    [Google Scholar]
  3. Heit JA, Colwell CW, Francis CW. Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement. Arch Intern Med. 2001; 161::22152221.
    [Google Scholar]
  4. Colwell CW, Berkowitz SD, Davidson BE. Randomized, double-blind comparison of ximelagatran, an oral direct thrombin inhibitor, and enoxaparin to prevent venous thromboembolism after total hip replacement (abstract). Blood. 2001; 98::706a.
    [Google Scholar]
  5. Ericksson BI, Arfwidsson AC, Frison L. A dose-ranging study of the oral direct thrombin inhibitor, ximelagatran, and its subcutaneous form, melagatran, compared with dalteparin in the prophylaxis of thromboembolism after hip or knee replacement: Metrhro I. Melagatran for Thrombin inhibition in Orthopedic surgery. Thromb Haemost. 2002; 87::231237.
    [Google Scholar]
  6. Ericksson BI, Bergqvist D, Kalebo P. Ximelagatran and melagatran compared with dalteparin for prevention of venous thromboembolism after total hip or knee replacement: the Methro II randomised trial. Lancet. 2002; 360::14411447.
    [Google Scholar]
  7. Ericksson BI, Agnelli G, Cohen AT. Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement. The Methro III study. Thromb Hemost. 2003; 89::288296.
    [Google Scholar]
  8. Ericksson BI, Agnelli G, Cohen AT: The oral direct thrombin inhibitor ximelagatran, and its subcutaneous form melagatran, compared with enoxaparin for prophylaxis of venous thromboembolism in total hip and total knee replacement: The Express Study (abstract). Presented at the 17th International Congress on Thrombosis; Italy, October (2002).
  9. Francis CW, Davidson BL, Berkowitz SD. Ximelagatran versus warfarin for the prevention of venous thromboembolism after total knee arthroplasty: a randomized, double-blind trial. Ann Intern Med. 2002; 137::648655.
    [Google Scholar]
  10. Francis CW, Berkowitz SD, Comp PC. Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med. 2003; 349::17031712.
    [Google Scholar]
  11. The Exult B Trial; The Second Phase III Trial to Compare Ximelagatran to Warfarin in Patients Undergoing Total Knee Replacement Surgery. Presented at The 45th Annual Meeting of the American Society of Hematology on December 6-9, (2003).
  12. Ericksson H, Wahlander K, Gustafsson D. A randomized controlled dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: Thrive I. J Thromb Hemost. 2003; 1::4147.
    [Google Scholar]
  13. Wahlander K, Lapidus L, Olsson CG. Thrive IV: an openlabel, pilot study of the treatment of pulmonary embolism with the oral direct thrombin inhibitor ximelagatran (abstract). Blood. 2001; 98::268a.
    [Google Scholar]
  14. Shulman S, Wahlander K, Lundstorm T. Secondary prevention of venous thromboembolism with the oral direct thrombic inhibitor ximelagatran. N Engl J Med. 2003; 349::17131721.
    [Google Scholar]
  15. Huisman MV. for the Thrive Treatment Study Investigators: Efficacy and safety of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for acute symptomatic deep vein thrombosis, with or without pulmonary embolism: a randomized, double-blind, multinational study. J Thromb Hemost. 2003; 1:Suppl 1:OC003.
    [Google Scholar]
  16. Salam AM. Rate control versus rhythm control for the management of atrial fibrillation: the verdict of the AFFIRM trial. Expert Opin Investig Drugs. 2003; 12::12311237.
    [Google Scholar]
  17. Petersen P, Grind M, Adler J. Ximelagatran versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: Sportif II: A dose-guiding, tolerability and safety study. J Am Coll Cardiol. 2003; 41::14451451.
    [Google Scholar]
  18. Peterson P, on behalf of the Sportif II and IV Investigators. A long-term follow-up of ximelagatran as an oral anticoagulant for the prevention of stroke and systemic embolism in patients with atrial fibrillation [abstract]. Presented at the 43rd Annual Meeting of the American Society of Hematology, Orlando, Florida, December 10, (2001).
  19.   Executive Steering Committee, on behalf of the Sportif III Investigators: Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): Randomized controlled trial. Lancet. 2003; 362::16911698.
    [Google Scholar]
  20. Halperin J, on behalf of the Sportif V Investigators: Efficacy and safety study of oral direct thrombin Inhibitor ximelagatran compared with dose-adjusted warfarin in the prevention of stroke and systemic embolic events in patients with atrial fibrillation (Sportif V) (abstract). Presented at the American Heart Association Annual Scientific Meeting, Orlando, Florida, November 9-12, 2003.
  21.   Antithhrombotic Trialists’ Collaboration: Collaborative metaanalysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002; 324::7186.
    [Google Scholar]
  22. Hurlem M, Abdelnoor M, Smith P. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002; 347::969974.
    [Google Scholar]
  23. Wallentin L, Wilcox RL, Weaver WD. Oral ximelagatran for secondary prophylaxis after myocardial infarction: The Esteemrandomized controlled trial. Lancet. 2003; 362::789797.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/qmj.2005.2.8
Loading
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error