Safety and efficacy of ximelagatran: Meta-analysis of the controlled randomized trials for the prophylaxis or treatment of venous thromboembolism

Current Pharmaceutical Design

Volumn 11, Issue 30, 2005, Pages 3893-3918

  Iorio, A ^a   Guercini, F ^a   Ferrante, F ^a   Nenci, G G ^a  

^a UNIVERSITY OF PERUGIA   (Italy)

Author keywords

Direct thrombin inhibitors; Joint replacement surgery; Low molecular weight heparin; Melagatran ximelagatran; Venous thromboembolism; Vitamin K antagonists

Indexed keywords

ANTIVITAMIN K; COUMARIN DERIVATIVE; DALTEPARIN; ENOXAPARIN; LOW MOLECULAR WEIGHT HEPARIN; MELAGATRAN; PLACEBO; WARFARIN; XIMELAGATRAN;

ACUTE HEART INFARCTION; BLEEDING; CARDIOGENIC SHOCK; CARDIOMYOPATHY; CLINICAL TRIAL; COHORT ANALYSIS; CONFIDENCE INTERVAL; DEEP VEIN THROMBOSIS; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; GASTROINTESTINAL HEMORRHAGE; HUMAN; ISCHEMIC COLITIS; LUNG EMBOLISM; LUNG INSUFFICIENCY; META ANALYSIS; METHODOLOGY; MORTALITY; PHLEBOGRAPHY; PNEUMONIA; POSTOPERATIVE PERIOD; PRIORITY JOURNAL; REVIEW; SEPTICEMIA; SYSTEMATIC REVIEW; TREATMENT OUTCOME; VENOUS THROMBOEMBOLISM;

ANTICOAGULANTS; AZETIDINES; BENZYLAMINES; ENDPOINT DETERMINATION; HUMANS; MEDLINE; POSTOPERATIVE HEMORRHAGE; PRODRUGS; QUALITY CONTROL; RANDOMIZED CONTROLLED TRIALS; THROMBOEMBOLISM; TREATMENT OUTCOME;

EID: 27744541985     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161205774580534     Document Type: Review

References (42)

1. Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA, et al. Sixth ACCP Consensus Conference on antithrombotic therapy. Prevention of venous thromboembolism. Chest 2001; 119(Suppl): 132S-175S.
2. Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Rashke R, et al. Heparin and low-molecular-weight heparin. Chest 2001; 119 (Suppl): 64S-94S.
3. Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulant: mechanism of action, clinical effectiveness and optimal therapeutic range. Chest 200 1; 119, (Suppl): 8S-21S.
4. Ansell J, Hirsh J, Dalen J, Bussey H, Anderson D, Poller L, et al. Managing oral anticoagulant therapy. Chest 2004; 119(Suppl): 22S-38S.
5. Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin independent inhibitors. J Clin Invest. 1990; 86(2): 385-91.
6. Gustafsson D, Nyström J-E, Carlsson S, Breberg U, Eriksson U, Gyzander E, et al. The direct thrombin inhibitor melagatran and its oral prodrug H 376/95: intestinal absorption properties, biochemical and pharmacodynamic effects. Thromb Res 2001; 101: 171-81
7. Eriksson UG, Bredberg U, Gislen K, Johansson LC, Frison L, Ahnoff M, et al. Pharmacokinetics and pharmacodynamics of Ximelagatran, a novel oral direct thrombin inhibitor, in young healthy male subjects. Eur J Clin Pharmacol 2003; 59: 35-43.
8. Johansson LC, Frison L, Logren U, Fager G, Gustafsson D, Eriksson UG. Influence of age on the pharmacokinetics and pharmacodynamics of Ximelagatran, an oral direct thrombin inhibitor. Clin Pharmacokinetics 2003; 42: 381-92.
9. Eriksson UG, Mandema JW, Karlsson MO, Frison L, Gislekog PO, Whalby U, et al. Pharmacokinetics of melagatran and the effect on ex vivo coagulation time in orthopedic surgery patients receiving subcutaneous melagatran and oral Ximelagatran: a population model analysis. Clin Pharmacokinetics 2003; 42: 687-701.
10. Raskob GE, Hirsh J. Controversies in timing of the first dose of anticoagulant prophylaxis against venous thromboembolism after major orthopedic surgery. Chest 2003; 124(6 Suppl): 379S-385S.
11. Zufferey P, Laporte S, Quenet S, Molliex S, Auboyer C, Decousus H, et al. Ximelagatran/melagatran versus LMWH in major orthopedic surgery: relationship between efficacy and safety and timing of initial administration. Path Thromb Haemost 2004; 33: 0C065.
12. Cohen AT, Agnelli G, Dahl OE, Erioksson BI, Kalebo P, Lassen MR, et al. Efficacy and safety of the treatment regimen of melagatran and ximelagatran for prevention of thromboembolic events after total hip or knee replacement: a meta-analysis of randomised, double-blind studies, to evaluate the influence of time and dose. J Thromb Haemost 2003; 1 (suppl): P1915.
13. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports or randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1-12.
14. Cochran WG. The combination of estimates from different experiments. Biometrics 1954; 10: 101-29.
15. Higgins PT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003, 327: 557-60.
16. Eriksson H, Eriksson UG, Frison L, Hansson PO, Held P, Holmstrom M, et al. Pharmacoknetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT. Thromb Haemostas 1999; 81: 358-63.
17. Colwell CW, Berkovitz SD, Davidson BL, Lotke PA, Ginsberg JS, Lieberman JR, et al. Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement. A randomized, double blind study. J Thromb Haemost 2003; 1: 2119-30.
18. Eriksson BI, Agnelli G, Cohen AT, Dahl OE, Lassen MR, Mouret P, et al. The direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement. The EXPRESS Study. Thromb Haemost 2003; 89: 288-96.
19. Eriksson BI, Bergqvist D, Kaleho P, Dahl OE, Lindbratt S, Bylock A, et al. Ximelagatran and melagatran compared with dalteparin for prevention of venous thromboembolism after total hip or knee replacement: The METHRO II randomized trial. Lancet 2002; 360: 1441-47.
20. Eriksson BI, Arfwidsson AC, Frison L, Eriksson UG, Bylock A, Kalebo P, et al. A dose-ranging study on the oral direct thrombin inhibitor, ximelagatran, and its subcutaneous form, melagatran, compared with dalteparin in the prophylaxis of thromboembolism after hip or knee replacement: METHRO I. Thromb Haemost 2002; 87: 231-7.
21. Eriksson BI, Agnelli G, Cohen AT, Dahl OE, Mouret P, Rosencher N, et al. 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 Haemost 2003; 89: 288-96.
22. Eriksson H, Wahlander K, Gustafsson D, Welin LT, Frison L, Schulman S, for the THRIVE Investigators. 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 Haemost 2003; 1: 41-47.
23. Francis CW, Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, et al. Comparison of Ximelagatran with Warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med 2003; 349; 18: 1703-12.
24. Francis CW, Davidson BL, Berkowitz SD, Lotke PA, Ginsberg S, Lieberman JR, et al. Ximelagatran versus warfarin for the prevention of venous thromboembolism after total knee arthroplasty. Ann Intern Med 2002; 137: 648-655.
25. Heit JA, Collwell CW, Francis CW, Ginsberg S, Berkowitz SD, Whipple J, et al. Comparison of the oral direct thrombin inhibitor Ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement a Phase 2 dose-finding study. Arch Intern Med 2001, 161: 2215-21.
26. Schulman S, Whalander K, Lundstrom T, Billing Clason S, Eriksson H, for the THRIVE III Investigators. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med 2003; 349: 1713-21.
27. Fiessinger JN, Huisman MV, Davidson BL, Bounameaux H, Francis CW, Eriksson H, et al. Ximelagatran vs Low-molecular-weight heparin and warfarin for treatment of deep vein thrombosis. A randomized trial. JAMA 2005; 293: 681-689.
28. Colwell CW, Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, et al. Randomized, double-blind comparison of ximelagatran, an oral direct thrombin inhibitor, and warfarin to prevent venous thromboembolism (VTE) after total knee replacement (TKR) EXULT B. Blood 2003; 102: 39a.
29. Committe for proprietary medicinal products (CPMP). Point to consider on clinical investigations of medicinal products for prophylaxis of intra- and post-operative venous thromboembolism. In: The European Agency for the Evaluation of Medicinal Products EMEA). London: CPW/EWP/7O7/98,2000.
30. Mismetti P, Laporte S, Zuffrey P, Epinat M, Decousus; H, Cucherat M. Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis. J Thromb Haemost 2004; 2(7):1058-70.
31. Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs. enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med 2002; 162(16): 1833-40.
32. Efron B, Morris C. Stein's paradox in statistics. Sci Am 1977; 236: 119-27.
33. Iorio A. Prevention of venous thromboembolisin, after major orthopedic surgery: summing up evidence about old and new antithrombotic agents. J Thromb Haemost 2004; 2(7): 1055-7.
34. Strebel N, Prins M, Agnelli G, Buller HR, Preoperative or postoperative start of prophylaxis for venous thromboembolism with low-molecular-weight heparin in elective hip surgery? Arch Intern Med 2002; 162(13): 1451-6.
35. Hull RD, Pineo GF, Stein PD, Mah AF, MacIsaac SM, Dahl OE, et al. Timing of initial administration of low-molecular-weight heparin prophylaxis against deep vein thrombosis in patients following elective hip arthroplasty: a systematic review. Arch Intern Med 2001; 161(16):1952-60.
36. Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Superiority of fondaparinux over enoxaparin in preventing venous thromboembolism in major orthopedic surgery using different efficacy end points. Chest 2004; 126(2): 501-8.
37. Turpie A, Bauer K, Eriksson B, Lassen M, Steering Committees of the Pentasaccharide Orthopedic Prophylaxis Studies. Efficacy and safety of fondaparinux in major orthopedic surgery according to the timing of its first administration. Thromb Haemost 2003; 90(2): 364-6.
38. Hull RD, Pineo GF, Francis C, Bergqvist D, Fellenius C, Soderberg K, et al. Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison. North American Fragmin Trial Investigators. Arch Intern Med 2000; 160(14): 2208-15.
39. Mismetti P. Prevention of venous thromboembolism after major orthopedic surgery: 'new' clinical trials for new antithrombotic agents. J Thromb Haemost 2003; 1(12): 2474-6.
40. Gould WR, Leadley RJ. Recent advances in the discovery and development of direct coagulation factor Xa inhibitors. Curr Pharm Design 2003; 9(28): 2337-47.
41. Graf J, Janssens U. Low-molecular weight heparins in percutaneous coronary interventions: current concepts, problems, and perspectives. Curr Pharm Design 2004; 10(4): 375-86.
42. Messmore HL, Coyne E, Wehrmacher WH, Demir AM, Fareed J. Studies comparing low molecular weight heparin with heparin for the treatment of thromboembolism: a literature review. Curr Pharm Design 2004; 10(9): 1001-10.