Antikoagulation: heute und in Zukunft

Ch. Vetter

doi:10.1055/s-0037-1619552

Hämostaseologie, Table of Contents

Hamostaseologie 2002; 22(03): 98-102
DOI: 10.1055/s-0037-1619552

Research Articles

Schattauer GmbH

Antikoagulation: heute und in Zukunft

Anticoagulation: the present and the future

Ch. Vetter

¹Deutsche bearbeitete Kurzfassung der Publikation: Anticoagulation – the present and the future. Clin Appl Thrombosis/Hemostasis 2001; 7: 195–204, von H. van Aken, Ch. Bode, H. Darius, C. Diehm, A. Encke, D. C. Gulba, S. Haas, W. Hacke, W. Puhl, M. Quante, H. Riess, R. Scharf, S. Schellong, K. Schrör, K.-L. Schulte, U. Tebbe

› Author Affiliations

Abstract

Zusammenfassung

Aufgrund seiner zentralen Rolle im Gerinnungsablauf ist Thrombin ein attraktives Zielenzym für dessen Hemmung. Mit der Entwicklung des direkten oralen Thrombininhibitors Ximelagatran gelang es, viele der Unzulänglichkeiten herkömmlicher Antikoagulanzien zu beseitigen, sodass diese Substanz die Anforderungen an ein ideales Antikoagulans weitestgehend erfüllt. Die antithrombotische Wirksamkeit und Verträglichkeit dieses Inhibitors wird zurzeit in einem weit gefächerten klinischen Studienprogramm untersucht.

Summary

Because of its central role in the coagulation cascade thrombin is an attractive target for its inhibition. Many limitations of conventional anticoagulants have been eliminated by the development of the direct oral thrombin inhibitor ximelagatran. Thus, this compound may fulfil the criteria of an ideal anticoagulant. The antithrombotic efficacy and safety of this inhibitor is presently studied in a large clinical development program.

Schlüsselwörter

Thrombininhibitor - Antikoagulanzien - Vitamin-K-Antagonisten - Thrombininhibition

Keywords

Thrombininhibitor - anticoagulants - vitamin K antagonists - thrombin inhibition

Full Text

References

Literatur
1 Bredberg U, Eriksson U, Taure K. et al. Effects of melagatran, a novel direct thrombin inhibitor, in healthy volunteers following intravenous, subcutaneous and oral administration. Blood 1999; 94 (Suppl. 01) 28a.
2 Carlsson S, Adler G, Elg M. The antithrombotic effects of the oral, direct thrombin inhibitor H 376/95 and other anticoagulants tested in a deep venous thrombosis treatment conscious rat model. Haemostasis 2000; 30 (Suppl. 01) 166.
3 Elg M, Gustafsson D, Carlsson S. Antithrombotic effects and bleeding time of thrombin inhibitors and warfarin in the rat. Thromb Res 1999; 94: 187-97.
4 Elg M, Gustafsson D, Deinum J. The importance of enzyme inhibition kinetics for the effect of thrombin inhibitors in a rat model of arterial thrombosis. Thromb Haemost 1997; 78: 1286-92.
5 Eriksson BI, Arfwidsson A-C, Frison L. et al. METHRO I: Dose ranging study H 376/95, a novel, oral, direct thrombin inhibitor, and its subcutaneous formulation, melagatran, for prophylaxis of venous thromboembolism after total hip and total knee replacement. Haemostasis 2000; 30 (Suppl. 01) 183.
6 Eriksson BI, Arfwidsson A-C, Sareyko Elvander C. et al. Subcutaneous and oral direct thrombin inhibitors for prophylaxis of deep venous thrombosis and pulmonary embolism after total hip and knee replacement. Blood 1999; 94 (10) (Suppl. 01) 589a.
7 Eriksson BI, Carlsson S, Halvarsson M. et al. Antithrombotic effect if two low molecular weight thrombin inhibitors and a low-molecular weight heparin in a caval vein thrombosis model in the rat. Thromb Haemost 1997; 78: 1404-7.
8 Eriksson BI, Ekman S, Kälebo P. et al. Prevention of deep-vein thrombosis after total hip replacement: direct thrombin inhibition with recombinant hirudin, CGP 39393. Lancet 1996; 347: 635-9.
9 Eriksson BI, Lindbratt S, Kälabo P. et al. METHRO II: Dose-response study of the novel oral, direct thrombin inhibitor, H 376/95, and its subcutaneous formulation melagatran, compared with dalteparin as thromboembolic prophylaxis after total hip replacement or total knee replacement. Haemostasis 2000; 30 (Suppl. 01) 20-1.
10 Eriksson H, Eriksson UG, Frison L. et al. Pharmacokinetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT. Thromb Haemost 1999; 81: 358-63.
11 Goldsack NR, Chambers RC, Dabbagh K. et al. Molecules in focus. Thrombin. Int J Biochem Cell Biol 1998; 30: 614-46.
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: 110-8.
13 Gustafsson D, Nyström J-E, Carlsson S. et al. Pharmacodynamic properties of H 376/95, a prodrug of the direct thrombin inhibitor melagatran, intended for oral use. Blood 1999; 94 (Suppl. 01) 26a.
14 Gustafsson D, Nyström J-E, Carlsson S. et al. Intestinal absorption properties and pharmacodynamic effects of the oral, direct thrombin inhibitor H 376/95 and its active form melagatran. Haemostasis 2000; 30 (Suppl. 01) 14.
15 Gustafsson D, Nyström J-E, Carlsson S. 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.
16 GUSTO IIa Investigators. Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. The Global Use of Strategies to Open Occluded Coronary Arteries. Circulation 1994; 90: 1631-7.
17 Hauptmann J, Stürzebecher J. Synthetic inhibitors of thrombin and factor Xa: From bench to bedside. Thromb Res 1999; 93: 203-41.
18 Hirsh J, Weitz JI. New antithrombotic agents. Lancet 1999; 353: 1431-6.
19 Li-Saw-Hee FL, Lip GYH. Melagatran. Curr Opin Cardiovasc Pulm Renal Investig Drugs 1999; 1: 88-92.
20 Mattsson C, Bjorkman J-A, Ulvinge J-C. Melagatran, hirudin and heparin as adjuncts to tissue-type plasminogen activator in a canine model of coronary artery thrombolysis. Fibrinol Proteol 1997; 11: 121-8.
21 Mehta JL, Chen L, Nichols WW. et al. Melagatran, an oral active-site inhibitor of thrombin, prevents or delays formation of electrically induced occlusive thrombus in the canine coronary artery. J Cardiovasc Pharmacol 1998; 31: 345-51.
22 Theroux P, Waters D, Lam J. et al. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med 1992; 327: 141-5.
23 Weitz J, Hudoba M, Messei D. et al. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 1990; 86: 385-91.
24 Weitz JI, Hirsch J. New antithrombotic agents. Chest 1999; 114: 715S-27S.