Ximelagatran, a new oral direct thrombin inhibitor, for the prevention of venous thromboembolic events in major elective orthopaedic surgery. Efficacy, safety and anaesthetic considerations

Anaesthesia

Volumn 59, Issue 8, 2004, Pages 803-810

  Rosencher, Nadia ^a  

^a Cochin Hospital ^*  (France)

Author keywords

Anticoagulants; Surgery: complications; Thromboembolism; Ximelagatran

Indexed keywords

ACETYLSALICYLIC ACID; ALANINE AMINOTRANSFERASE; ANESTHETIC AGENT; ANTICOAGULANT AGENT; ANTITHROMBOCYTIC AGENT; ANTIVITAMIN K; BLOOD CLOTTING FACTOR 10A INHIBITOR; DALTEPARIN; DESULFATOHIRUDIN; ENOXAPARIN; FONDAPARINUX; HEPARIN; HIRUDIN; LOW MOLECULAR WEIGHT HEPARIN; MELAGATRAN; NONSTEROID ANTIINFLAMMATORY AGENT; THROMBIN INHIBITOR; VITAMIN K GROUP; WARFARIN; XIMELAGATRAN; AZETIDINE DERIVATIVE; BENZYLAMINE DERIVATIVE; THROMBIN;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANESTHESIA; ANTICOAGULANT THERAPY; BLEEDING; BLOOD CLOTTING; CLINICAL TRIAL; DOSE TIME EFFECT RELATION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG INDICATION; DRUG SAFETY; DRUG TOLERABILITY; DRUG USE; ELECTIVE SURGERY; EUROPE; FOOD DRUG INTERACTION; HUMAN; INTERMETHOD COMPARISON; MAJOR SURGERY; ORTHOPEDIC SURGERY; PATIENT MONITORING; PHARMACODYNAMICS; POSTOPERATIVE PERIOD; PREDICTION; REVIEW; RISK ASSESSMENT; SIDE EFFECT; SPINAL ANESTHESIA; SPINAL CORD HEMORRHAGE; STANDARD; THROMBOCYTOPENIA; THROMBOSIS PREVENTION; VENOUS THROMBOEMBOLISM; DRUG ANTAGONISM; METHODOLOGY; ORAL DRUG ADMINISTRATION; POSTOPERATIVE COMPLICATION; THROMBOEMBOLISM; VEIN THROMBOSIS;

ADMINISTRATION, ORAL; ANESTHESIA; ANTICOAGULANTS; AZETIDINES; BENZYLAMINES; CLINICAL TRIALS; HUMANS; ORTHOPEDIC PROCEDURES; POSTOPERATIVE COMPLICATIONS; THROMBIN; THROMBOEMBOLISM; VENOUS THROMBOSIS;

EID: 4344701089     PISSN: 00032409     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1365-2044.2004.03840.x     Document Type: Review

References (55)

1. Geerts WH, Heir JA, Clagett GP et al. Sixth ACCP Consensus Conference on antithrombotic therapy. Prevention of venous thromboembolism. Chest 2001; 119 (Suppl.): 132S-75S.
2. Hull RD, Pineo GF, Francis C et al. for the North American Fragmin Trial Investigators. Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients. A double-blind, randomized comparison. Archives of Internal Medicine 2000; 160: 2199-207.
3. Hull RD, Pineo GF, Stein PD 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. Archives of Internal Medicine 2001; 161: 1952-60.
4. Liu S, Carpenter RL, Neal JM. Epidural anesthesia and analgesia. Their role in postoperative outcome. Anaesthesiology 1995; 82: 1474-506.
5. Ostendorf M, Johnell O, Malchau H et al. The epidemiology of total hip replacement in the Netherlands and Sweden: present status and future needs. Acta Orthopaedica Scandinavica 2002; 71: 433-9.
6. Robertsson O, Dunbar MJ, Knutson K et al. Past incidence and future demand for knee arthroplasty in Sweden: a report from the Swedish Knee Arthroplasty Register regarding the effect of past and future population changes on the number of arthroplasties performed. Acta Orthopaedica Scandinavica 2000; 71: 376-80.
7. Cohen AT, Bailey CS, Alikhan R, Cooper DJ. Extended thromboprophylaxis with low molecular weight heparin reduces symptomatic venous thromboembolism following lower limb arthroplasty - a meta-analysis. Thrombosis and Haemostasis 2001; 85: 940-1.
8. Eikelboom JW, Quinlan DJ, Douketis JD. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials. Lancet 2001; 358: 9-15.
9. Hirsh J. Oral anticoagulant drugs. New England Journal of Medicine 1991; 324: 1865-75.
10. Hirsh J, Dalen JE, Anderson DR et al. Oral anticoagulants. Mechanism of actions, clinical effectiveness and optimal therapeutic range. Chest 1998; 114: 445S-69S.
11. Wells PS, Holbrook AM, Crowther NR et al. Interactions of warfarin with drugs and food. Annals of Internal Medicine 1994; 121: 676-83.
12. Hull R, Delmore T, Genton E et al. Warfarin sodium versus low-dose heparin in the long-term treatment of venous thrombosis. New England Journal of Medicine 1979; 301: 855-8.
13. Hirsh J, Warkentin TE, Raschke R et al. Heparin and low-molecular weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy and safety. Chest 1998; 14: 489S-510S.
14. Turpie AG. Pharmacology of the low molecular weight heparins. American HeartJournal 1998; 135 (6 part; 3 Suppl.): 329-35.
15. Theroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after the discontinuation of heparin. New England Journal of Medicine 1992; 327: 141-5.
16. Donat F, Duret JP, Santom A et al. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clinical Pharmacokinetics 2002; 41 (Suppl. 2): 1-9.
17. O'Hara DA, Duff A, Berlin JA et al. The effect of anesthetic technique on postoperative outcomes in hip fracture repair. Anesthesiology 2000; 92: 947-57.
18. Sutcliffe AJ, Parker M. Mortality after spinal and general anaesthesia for surgical fixation of hip fractures. Anaesthesia 1994; 49: 237-40.
19. Sorenson RM, Pace NL. Anesthetic techniques during surgical repair of femoral neck fractures. A Meta-Analysis. Anesthesiology 1992; 77: 1095-104.
20. Rodgers A, Walker N, Schug S et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials. British Medical Journal 2000; 321: 1493-504.
21. Narchi P. Spinal anaesthesia and the use of anticoagulants. Best Practice and Research Clinical Anaesthesiology 2003; 17: 443-9.
22. Tryba M. European practice guidelines: thromboembolism prophylaxis and regional anesthesia. Regional Anesthesia and Pain Medicine 1998; 23 (Suppl. 2): 178-82.
23. Dahl OE, Aspelin T, Lyberg T. The role of bone traumatization in the initiation of proximal deep vein thrombosis during cemented hip replacement surgery in pigs. Blood Coagulation and Fibrinolysis 1995; 6: 709-17.
24. Turpie AG, Bauer KA, Eriksson BI, Lassen MR. PENTATHALON 2000 Study Steering Committee. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomized double-blind trial. Lancet 2002; 359: 1721-6.
25. Horlocker TT. Low-molecular-weight heparins. New England Journal of Medicine 1998; 338: 687-8.
26. Wysowski DK, Talarico L, Bacsanyi J, Botstein P. Spinal and epidural hematoma and low-molecular-weight heparin. New England Journal of Medicine 1998; 338: 1774-5.
27. Dolenska S. Neuroaxial blocks and LMWH thromboprophylaxis. Hospital Medicine 1998; 59: 940-3.
28. Tryba M. Epidural regional anaesthesia and low molecular heparin. Pro. Anaesthesiologie Intensivmedizin Notfallmedizin Schmerztherapie 1993; 28: 179-81.
29. Tryba M, Wedel DJ. Central neuraxial block and low molecular weight heparin (enoxaparin): lessons learned from different dosage regimes in two continents. Acta Anaesthesiologica Scandinavica 1997; 111 (Suppl.): 100-4.
30. Schroeder DR. Statistics: detecting a rare adverse drug reaction using spontaneous reports. Regional Anesthesia and Pain Medicine 1998; 23: 183-9.
31. Gustafsson D, Antonsson T, Bylund R et al. Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes. Thrombosis and Haemostasis 1998; 79: 110-8.
32. Sarich TC, Wolzt M, Eriksson UG et al. Effects of ximelagatran, an oral direct thrombin inhibitor, r-hirudin and enoxaparin on thrombin generation and platelet activation in healthy male subjects. Journal of the American College of Cardiology 2003; 41: 557-64.
33. Carlsson S, Elg M, Mattsson C. Effects of ximelagatran, the oral form of melagatran, in the treatment of caval vein thrombosis in conscious rats. Thrombosis Research 2002; 107: 163-8.
34. Klement P, Carlsson S, Rak J et al. The benefit-to-risk profile of melagatran is superior to that of hirudin in a rabbit arterial thrombosis prevention and bleeding model. Journal of Thrombosis Haemostasis 2003; 1: 587-94.
35. Sarich TC, Osende JI, Eriksson UG et al. Acute antithrombotic effects of ximelagatran, an oral direct thrombin inhibitor, and r-hirudin in a human ex vivo model of arterial thrombosis. Journal of Thrombosis and Haemostasis 2003; 1: 999-1004.
36. Elg M, Gustafsson D, Carlsson S. Antithrombotic effects and bleeding time of thrombin inhibitors and warfarin in the rat. Thrombosis Research 1999; 94: 187-97.
37. Eriksson UG, Bredberg U, Gislen K et al. Pharmacokinetics and pharmacodynamics of ximelagatran, a novel oral direct thrombin inhibitor, in young healthy male subjects. European Journal of Clinical Pharmacology 2003; 59: 35-43.
38. Eriksson UG, Mandema J, Karlsson MO et al. Pharmacokinetics of melagatran and the effect on ex vivo coagulation time in orthopaedic surgery patients receiving subcutaneous melagatran and oral ximelagatran. A population model analysis. Clinical Pharmacokinetics 2003; 42: 687-701.
39. Wåhlander K, Lapidus L, Olsson CG et al. Pharmacokinetics, pharmacodynamics and clinical effects of the oral direct thrombin inhibitor ximelagatran in acute treatment of patients with pulmonary embolism and deep vein thrombosis. Thrombosis Research 2002; 107: 93-9.
40. Wolzt M, Wollbratt M, Svensson M et al. Consistent pharmacokinetics of the oral direct thrombin inhibitor ximelagatran in patients with nonvalvular atrial fibrillation and in healthy subjects. European Journal of Clinical Pharmacology 2003; 59: 537-43.
41. Johansson LC, Frison L, Logren U et al. Influence of age on the pharmacokinetics and pharmacodynamics of ximelagatran, an oral direct thrombin inhibitor. Clinical Pharmacokinetics 2003; 42: 381-92.
42. Johansson L, Andersson M, Fager G et al. No influence of ethnic origin on the pharmacokinetics and pharmacodynamics of melagatran following oral administration of ximelagatran, a novel oral direct thrombin inhibitor, to healthy male volunteers. Clinical Pharmacokinetics 2003; 42: 475-84.
43. Sarich TC, Teng R, Peters GR et al. No influence of obesity on the pharmacokinetics and pharmacodynamics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran. Clinical Pharmacokinetics 2003; 42: 485-92.
44. Wåhlander K, Eriksson-Lepkowska M, Frison L et al. No influence of mild-to-moderate hepatic impairment on the pharmacokinetics and pharmacodynamics of ximelagatran, an oral direct thrombin inhibitor. Clinical Pharmacokinetics 2003; 42: 755-64.
45. Eriksson UG, Johansson S, Attman P-O et al. Influence of severe renal impairment on the pharmacokinetics and pharmacodynamics of oral ximelagatran and subcutaneous melagatran. Clinical Pharmacokinetics 2003; 42: 743-53.
46. Johansson S, Schützer K-J, Kessler M-E et al. No influence of alcohol intake on the pharmacokinetics or pharmacodynamics of the oral direct thrombin inhibitor, ximelagatran, in healthy volunteers. Journal of Thrombosis and Haemostasis 2003; 1 (Suppl. 1): P1991.
47. Bredberg E, Andersson TB, Frison L et al. Ximelagatran, an oral direct thrombin inhibitor, has a low potential for cytochrome P450-mediated drug-drug interactions. Clinical Pharmacokinetics 2003; 42: 765-77.
48. Francis CW, Berkowitz SD, Comp PC et al. Comparison of the oral direct thrombin inhibitor ximelagatran with warfarin for the prevention of venous thromboembolism following total knee replacement. EXULT A. New England Journal of Medicine 2003; 349: 1703-12.
49. Colwell CW, Berkowitz SD, Comp PC 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: 14a.
50. Eriksson BI, Bergqvist D, Kälebo P et al. Melagatran for Thrombin inhibition in Orthopaedic surgery. 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: 1441-7.
51. Cohen AT, Agnelli G, Dahl OE et al. Efficacy and safety of the treatment regimen of melagatran and ximelagatran for prevention of thrornboembolic events after total hip or knee replacement: a meta-analysis of 3 randomized, double-blind studies, to evaluate the influence of time and dose. Journal of Thrombosis and Haemostasis 2003; 1 (Suppl. 1): July): P1915.
52. Eriksson BI, Agnelli G, Cohen AT 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. Thrombosis and Haemostasis 2003; 89: 288-96.
53. Dahl OE, Eriksson BI, Agnelli G et al. Efficacy and safety of post operative Ximelagratran for prevention of thromboembolism across different orthopaedic surgery patient groups. Pathophysiology of Haemostasis and Thrombosis 2004 abstract; in press:.
54. Eriksson BI, Agnelli G, Cohen AT et al. on behalf of the EXPRESS Study Group. 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. Journal of Thrombosis and Haemostasis 2003; 1: 2490-6.
55. Schulman S, Wahlander K, Lundstrom T, Clason SB, Eriksson H, THRIVE III InvestigatorS. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. New England Journal of Medicine 2003; 349: 1713-21.