Journal of Thrombosis and Thrombolysis

, Volume 13, Issue 1, pp 41–47

Argatroban

  • Sekar Kathiresan
  • Jin Shiomura
  • Ik-Kyung Jang
Article

Abstract

Antithrombotic and antiplatelet therapies are the cornerstones of management of cardiovascular disorders today. Due to the safety and efficacy limitations of the classic antithrombotic, unfractionated heparin, considerable effort has been directed at developing novel anticoagulants. Direct thrombin inhibitors as a class of drugs offer inhibition of clot-bound as well as fluid-phase thrombin and a more predictable anticoagulant response. Specifically, argatroban, a synthetic small molecule direct thrombin inhibitor, selectively inhibits the catalytic site of thrombin in a reversible manner. Overall, argatroban's short half-life, ease of monitoring with an activated partial thromboplastin time, and safety in renal failure patients make this drug the preferable mode therapy for prevention of thrombosis in heparin-induced thrombocytopenia. The role of adjunctive argatroban therapy in acute coronary syndromes and during percutaneous coronary intervention is currently being studied.

argatroban anticoagulation direct thrombin inhibitor 

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References

  1. 1.
    McLean J. The thromboplastic action of cephalin. Am J Physiol 1916;41:250–257.Google Scholar
  2. 2.
    Hirsh J, Raschke R, Warkentin TE, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1995;108:258S–275S.Google Scholar
  3. 3.
    Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 2000;407:258–264.Google Scholar
  4. 4.
    Sabatine MS, Jang IK. Antithrombotic therapy in acute coronary syndromes. Acta Cardiol 1999;54:3–29.Google Scholar
  5. 5.
    Hirsh J. New anticoagulants. Am Heart J 2001;142:S3–S8.Google Scholar
  6. 6.
    Hursting MJ, Alford KL, Becker JC, et al. Novastan (brand of argatroban): a small molecule, direct thrombin inhibitor. Semin Thromb Hemost 1997;23:503–516.Google Scholar
  7. 7.
    Berry CN, Girardot C, Lecoffre C, Lunven C. Effects of the synthetic thrombin inhibitor argatroban on fibrinor clot-incorporated thrombin: comparison with heparin and recombinant hirudin. Thromb Haemost 1994;72:381–386.Google Scholar
  8. 8.
    Hantgan RR, Jerome WG, Hursting MJ. No effect of clot age or thrombolysis on argatroban' inhibition of thrombin. Blood 1998;92:2064–2074.Google Scholar
  9. 9.
    Kondo LM, Wittkowsky AK, Wiggins BS. Argatroban for the prevention and treatment of thromboembolism in heparin-induced thrombocytopenia. Ann Pharmacother 2001;35:440–451.Google Scholar
  10. 10.
    Swan SK, St Peter JV, Lambrecht LJ, Hursting MJ. Comparison of anticoagulant effects and safety of argatroban and heparin in healthy subjects. Pharmacotherapy 2000;20:756–770.Google Scholar
  11. 11.
    Swan SK, Hursting MJ. The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender, and hepatic or renal dysfunction. Pharmacotherapy 2000;20:318–319.Google Scholar
  12. 12.
    Schwartz RP, Becker JP, Brooks RL, et al. The preclinical and clinical pharmacology of Novastan (argatroban): a small molecule, direct thrombin inhibitor. Clin Appl Thromb Hemost 1997;3:1–15.Google Scholar
  13. 13.
    Data on file. Argatroban Prescribing Information. Philadelphia: Smith-Kline Beecham, 2000.Google Scholar
  14. 14.
    Okamoto S, Hijikata A, Kikumoto R, et al. Potent inhibition of thrombin by the newly synthesized arginine derivative No. 805: the importance of stereostructure of its hydrophobic carboxamide portion. Biochem Biophys Res Commun 1981;101:440–446.Google Scholar
  15. 15.
    Jang IK, Gold HK, Leinbach RC, Fallon JT, Collen D. In vivo thrombin inhibition enhances and sustains arterial recanalization with recombinant tissue-type plasminogen activator. Circ Res 1990;67:1552–1561.Google Scholar
  16. 16.
    Jang IK, Gold HK, Ziskind AA, Leinbach RC, Fallon JT, Collen D. Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition. Circulation 1989;81:219–225.Google Scholar
  17. 17.
    Jang IK, Gold HK, Leinbach RC, et al. Persistent inhibition of arterial thrombosis by a 1-hour intravenous infusion of argatroban, a selective thrombin inhibitor. Coron Artery Dis 1992;3:407–414.Google Scholar
  18. 18.
    Yasuda T, Gold HK, Yaoita H, et al. Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein IIb/IIIa antibody on coronary artery reperfusion, reocclusion, and bleeding with recombinant tissue-type plasminogen activator in a canine preparation. J Am Coll Cardiol 1990;16:714–722.Google Scholar
  19. 19.
    Jang IK, Brown DF, Giugliano RP, et al. A multi-center, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (tPA) in acute myocardial infarction: myocardial infarction with novastan and tPA (MINT) study. J Am Coll Cardiol 1999;33:1880–1885.Google Scholar
  20. 20.
    Vermeer F, Vahanian A, Fels PW, et al. Argatroban and alteplase in patients with acute myocardial infarction: the ARGAMI study. J Thromb and Thrombolysis 2000;10:233–240.Google Scholar
  21. 21.
    Behar S, Hod H, Kaplinsky E, for the ARGAMI-2 Study Group. Argatroban versus heparin as adjuvant therapy to thrombolysis for acute myocardial infarction: safety considerations-ARGAMI-2 study [abstract]. Circulation 1998;98(1, suppl):I453–I454.Google Scholar
  22. 22.
    Cody RJ-Results from late breaking clinical trials session at ACC'97. J Am Coll Cardiol 1997;30:1–7.Google Scholar
  23. 23.
    Gold HK, Torres FW, Garabedian HD, et al. Evidence for a rebound coagulation phenomenon after cessation of a 4-hour infusion of a specific thrombin inhibitor in pa-tients with unstable angina pectoris. J Am Coll Cardiol 1993;21:1039–1047.Google Scholar
  24. 24.
    Theroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med 1992;327:141–145.Google Scholar
  25. 25.
    Januzzi JL, Jang IK. Heparin induced thrombocytopenia: diagnosis and contemporary antithrombin management. J Thromb and Thrombolysis 1999;7:259–264.Google Scholar
  26. 26.
    Lewis BE, Wallis DE, Berkowitz SD, et al. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation 2001;103:1838–1843.Google Scholar
  27. 27.
    Herrman JR, Suryapranata H, den Heijer P, Gabriel L, Kutryk MJ, Serruys PW. Argatroban during percutaneous transluminal coronary angioplasty: results of a dose-verification study. J Thromb and Thrombolysis 1996;3:367–375.Google Scholar
  28. 28.
    Lewis BE, Matthai W, Grassman ED, et al. Results of a Phase 2/3 trial of argatroban anticoagulation during PTCA of patients with heparin-induced thrombocytopenia [abstract]. Circulation 1997;96(8, suppl 1):I217.Google Scholar
  29. 29.
    Kobayashi S, Tazaki Y. Effect of the thrombin inhibitor argatroban in acute cerebral thrombosis. Semin Thromb and Hemost 1997;23:531–534.Google Scholar
  30. 30.
    Matsuo T, Kario K, Matsuda S, Yamaguchi N, Kakishita E. Effect of thrombin inhibition on patients with peripheral arterial obstructive disease: a multicenter clinical trial of argatroban. J Thromb Thrombolysis 1995;2:131–136.Google Scholar
  31. 31.
    Ohteki H, Furukawa K, Ohnishi H, Narita Y, Sakai M, Doi K. Clinical experience of argatroban for anticoagulation in cardiovascular surgery. Jpn J Thorac Cardiovasc Surg 2000;48:39–46.Google Scholar
  32. 32.
    Kawada T, Kitagawa H, Hoson M, Okada Y, Shiomura J. Clinical application of argatroban as an alternative anticoagulant for extracorporeal circulation. Hematol Oncol Clin North Am 2000;14:445–457.Google Scholar
  33. 33.
    Hursting MJ, Zehnder JL, Joffrion JL, Becker JC, Knappenberger GD, Schwarz RP. The international normalized ratio during concurrent warfarin and argatroban anticoagulation: differential contributions of each agent and effects of the choice of thromboplastin used. Clin Chem 1999;45:409–412.Google Scholar
  34. 34.
    Sheth SB, DiCicco RA, Hursting MJ, Montague T, Jorkasky DK. Interpreting the international normalized ratio (INR) in individuals receiving argatroban and warfarin. Thromb Haemost 2001;85:435–440.Google Scholar
  35. 35.
    Cannon CP, Weintraub WS, Demopoulos LA, et al. TACTICS (treat angina with aggrastat and determine cost of therapy with an invasive or conservative strategy)- Thrombolysis In Myocardial Infarction 18 investigators: comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001;344:1879–1887.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Sekar Kathiresan
    • 1
  • Jin Shiomura
    • 2
  • Ik-Kyung Jang
    • 1
  1. 1.Cardiology DivisionMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Mitsubishi Pharma CorporationTokyoJapan

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