RSS-Feed abonnieren
DOI: 10.1055/s-2004-829006
© Georg Thieme Verlag Stuttgart · New York
Prophylaxe und Therapie der tiefen Beinvenenthrombose mit Ximelagatran
Prevention and treatment of deep vein thrombosis with ximelagatranPublikationsverlauf
eingereicht: 14.11.2003
akzeptiert: 18.3.2004
Publikationsdatum:
21. Juli 2004 (online)

Heparine sind hochwirksam und vielfach Therapiestandard zur Thromboembolie-Prophylaxe nach Operationen, schweren Traumata und in internistischen Risikosituationen. Bei manifesten tiefen Venenthrombosen sind Heparine wirksam zur Verhinderung von Lungenembolien wie auch von Rezidiven. Die Heparintherapie wird üblicherweise überlappend ersetzt durch eine orale Antikoagulation (OAK) mit Vitamin-K-Antagonisten (Phenprocoumon oder Warfarin). Hauptprobleme dieser Substanzen sind ihr enges therapeutisches Fenster, das regelmäßige Laborkontrollen erfordert, sowie ihre Wechselwirkungen mit zahlreichen anderen Medikamenten.
Die Behandlungsmodalitäten der tiefen Beinvenenthrombose haben sich in den letzten Jahren deutlich gewandelt. Die Initialtherapie wurde durch die niedermolekularen Heparine (NMH) vereinfacht. Bettruhe wird eher als Risiko denn als notwendige Maßnahme zur Vermeidung embolischer Ereignisse angesehen. Ein Großteil auch proximaler Thrombosen wird primär außerhalb von Krankenhäusern diagnostiziert und behandelt.
Mit dem direkten Thrombinantagonisten Melagatran rückt ein neues Therapieprinzip in den Bereich der klinischen Anwendung, das sich in oraler Form einsetzen lässt und damit auch für ein ambulantes Therapiekonzept der tiefen Beinvenenthrombose eignet.
Literatur
- 1
Bauer K A, Eriksson B I, Lassen M R, Turpie A GG.
Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism
after elective hip-replacement surgery: a randomised double blind trial.
N Engl J Med.
2001;
345
1305-1310
MissingFormLabel
- 2
Elg M, Carlsson S, Gustafsson D.
Effect of activated prothrombin complex concentrate or recombinant factor VIIa
on the bleeding time and thrombus formation during anticoagulation with a direct
thrombin inhibitor.
Thromb Res.
2001;
101
145-157
MissingFormLabel
- 3
Elg M, Gustafsson D, Carlsson S.
Antithrombotic effects and bleeding time of thrombin inhibitors and warfarin
in the rat.
Thromb Res.
1999;
94
187-197
MissingFormLabel
- 4
Eriksson B I, Agnelli G, Cohen A. 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
288-296
MissingFormLabel
- 5
Eriksson B I, Agnelli G, Cohen A T. 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.
J Thromb Haemost.
2003;
1
2490-2496
MissingFormLabel
- 6
Eriksson B I, Arfwidsson A C, Frison L. et al .
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: METHRO I.
Thromb Haemost.
2002;
87
231-237
MissingFormLabel
- 7
Eriksson B I, Bergqvist D, Kälebo P. et al .
Ximelagatran and melagatran compared with dalteparin for the prevention of venous
thromboembolism after total hip or knee replacement: the METHRO II randomised
trial.
Lancet.
2002;
360
1441-1447
MissingFormLabel
- 8
Eriksson H, Eriksson U G, Frison L. et al .
Pharmacokinetics and pharmacodynamics of Melagatran, a novel, synthetic LMW
thrombin inhibitor, in patients with acute DVT.
Thromb Haemost.
1999;
81
358-363
MissingFormLabel
- 9
Eriksson H, Wahlander K, Gustafsson D. et al .
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
MissingFormLabel
- 10
Eriksson U G, Liljenvald A C, Fager G, Thuresson A.
The pharmacokinetics, metabolism and elimination of H 376/95, a novel, direct
thrombin inhibitor in healthy male subjects, after oral and intravenous
administration.
Pharmacotherapy.
2000;
20
1264
MissingFormLabel
- 11
Eriksson U G, Bredberg U, Hoffmann K J. et al .
Absorption, distribution, metabolism, and excretion of ximelagatran, an oral
direct thrombin inhibitor, in rats, dogs, and humans.
Drug Metab Dispos.
2003;
31
294-305
MissingFormLabel
- 12
Gustafsson D, Antonsson T, Bylund R. et al .
Effects of Melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin
and fibrinolytic enzymes.
Thromb Haemost.
1998;
79
110-118
MissingFormLabel
- 13
Gustafsson D, Nystrom J, Carlsson S. et al .
The direct thrombin inhibitor melagatran and its oral prodrug H 376/95: Intestinal
absorption properties, biochemical and pharmacodynamical effects.
Thromb Res.
2001;
101
171-181
MissingFormLabel
- 14
Harenberg J, Fenyvesi T, Jörg I.
Ximelagatran zur Therapie thrombembolischer Erkrankungen.
Hämostaseologie.
2002;
22
107-111
MissingFormLabel
- 15
Heit J A, Colwell C W, Francis C W. et al .
Comparison of the oral direct thrombin inhibitor Ximelagatran with Enoxaparin
as prophylaxis against venous thromboembolism after total knee replacement.
Arch Intern Med.
2001;
161
2215-2221
MissingFormLabel
- 16
Hirsh J, Warkentin T E, Shaughnessy S G. et al .
Heparin and low molecular heparin: Mechanisms of action, pharmacokinetics, dosing,
monitoring, efficacy and safety.
Chest.
2001;
119
564-594
MissingFormLabel
- 17
Hull R D, Pineo G F, Stein P D. 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 Int Med.
2001;
161
1952-1960
MissingFormLabel
- 18
Huisman M V.
Efficacy and safety of the oral direct thrombin inhibitor ximelagatran compared
with current standard therapy for acute symptomatic deep vein thrombosis, with
or without pulmonary embolism: a randomized, double-blind multinational study
(Abstract).
Thromb Haemost.
2003;
(Suppl 1)
OC003
MissingFormLabel
- 19
Jeske W, Walenga J M, Lewis B E. et al .
Pharmacology of argatroban.
Exp Opin Invest Drugs.
1999;
8
625-654
MissingFormLabel
- 20
Johansson L C, Frison L, Logren U. et al .
Influence of age on the pharmacokinetics and pharmacodynamics of ximelagatran,
an oral direct thrombin inhibitor.
Clin Pharmacokinet.
2003;
42
381-392
MissingFormLabel
- 21
Kearon C, Gent M, Hirsh J. et al .
A comparison of three months of anticoagulation with extended anticoagulation
for a first episode of idiopathic venous thromboembolism.
N Engl J Med.
1999;
340
901-907
MissingFormLabel
- 22
Kearon C, Ginsberg J S, Kovacs M J. et al .
Comparison of low-intensity warfarin therapy for long-term prevention of recurrent
venous thromboembolism.
N Engl J Med.
2003;
349
631-639
MissingFormLabel
- 23
Lassen M R, Bauer K A, Eriksson B I, Turpie A GG. for the European Pentasaccharide Hip Elective Surgery Study (EPHESUS) Steering
Committee .
Postoperative fondaparinux versus preoperative enoxaparin for prevention of
venous thromboembolism in elective hip replacement surgery: a randomised double-blind
comparison.
Lancet.
2002;
259
1715-1720
MissingFormLabel
- 24
Sarich T C, Eriksson U G, Mattson C. et al .
Inhibition of thrombin generation by the oral direct thrombin inhibitor Ximelagatran
in shed blood from healthy male subjects.
Thromb Haemost.
2002;
87
300-305
MissingFormLabel
- 25
Schulman S, Wahlander K, Lundstrom T. et al .
Secondary prevention of venous thromboembolism with the oral direct thrombin
inhibitor Ximelagatran.
N Engl J Med.
2003;
349
1713-1721
MissingFormLabel
- 26
Sorbera L A, Bayès M, Castañer J, Silvestre J.
Melagatran and Ximelagatran.
Drugs of the future.
2001;
26
1155-1170
MissingFormLabel
- 27
Steinmetzer T, Hauptmann J, Stürzebecher J.
Advances in the development of thombin inhibitors.
Exp Opin Invest Drugs.
2001;
10
845-864
MissingFormLabel
- 28
Wahlander K, Lapidus L, Olsson C G. 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.
Thromb Res.
2002;
107
93-99
MissingFormLabel
Priv.-Doz. Dr. med. Ludwig Caspary
Angiologische Gemeinschaftspraxis
Luisenstraße 10/11
30159 Hannover
Telefon: 0511/3681830
Fax: 0511/3681930
eMail: LCaspary@t-online.de