Compdrison of argatroban and hirudin for the reperfusion of thrombotic arterial occlusion by tissue plasminogen activator

Theodore J. Boeve, Guy Reed, Nilto Carias De Oliveira, James Titus, Stefan Janssens, Robert P. Giugliano, David Torchiana, Willard Daggett, Richard Schwarz, Ik Kyung Jang

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Abstract

Despite theoretical advantages of direct thrombin inhibitors, recent clinical studies failed to show the superiority of hirudin over heparin in patients with acute coronary syndromes. However, these inhibitors have important in vitro differences for the inhibition of clot-bound thrombin that may translate into different in vivo relative efficacy. The effects of two direct thrombin inhibitors, argatroban and hirudin, on the reperfusion of thrombotic arterial occlusion by t-PA were compared. In anesthetized rabbits thrombotic occlusion was induced in the femoral artery. t-PA, aspirin, and various doses of argatroban (1.25, 2.5, and 5.0 mg/kg/h) or hirudin (2.5 and 5.0 mg/kg/h) were administered (six animals in each group). Blood flow was measured for 4 hours. Animals treated with 2.5 mg argatroban more rapidly achieved full reperfusion than those treated with high-dose argatroban or hirudin (P < 0.05). At the doses that induced comparable prolongation of bleeding time, argatroban showed a significantly faster and higher level of reperfusion than hirudin. In animals treated with hirudin, there was a positive correlation between the aPTT and the mean reperfusion blood flow (r = 0.70, P < 0.05). In animals treated with argatroban, this correlation did not exist and the high-dose argatroban was paradoxically less effective in promoting thrombolysis despite greater anticoagulation effects. In this animal model of arterial thrombosis, argatroban was more effective than hirudin in inducing rapid, full reperfusion with t-PA. Although they are both direct thrombin inhibitors, these two agents showed important dose-related differences in efficacy and anticoagulant effects.

Original languageEnglish (US)
Pages (from-to)103-108
Number of pages6
JournalJournal of Thrombosis and Thrombolysis
Volume6
Issue number2
DOIs
StatePublished - Jan 1 1998

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Hirudins
Tissue Plasminogen Activator
Reperfusion
Antithrombins
Bleeding Time
argatroban
Femoral Artery
Acute Coronary Syndrome
Thrombin
Anticoagulants
Aspirin
Heparin
Thrombosis
Animal Models
Rabbits

All Science Journal Classification (ASJC) codes

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Boeve, T. J., Reed, G., Carias De Oliveira, N., Titus, J., Janssens, S., Giugliano, R. P., ... Jang, I. K. (1998). Compdrison of argatroban and hirudin for the reperfusion of thrombotic arterial occlusion by tissue plasminogen activator. Journal of Thrombosis and Thrombolysis, 6(2), 103-108. https://doi.org/10.1023/A:1008889202725

Compdrison of argatroban and hirudin for the reperfusion of thrombotic arterial occlusion by tissue plasminogen activator. / Boeve, Theodore J.; Reed, Guy; Carias De Oliveira, Nilto; Titus, James; Janssens, Stefan; Giugliano, Robert P.; Torchiana, David; Daggett, Willard; Schwarz, Richard; Jang, Ik Kyung.

In: Journal of Thrombosis and Thrombolysis, Vol. 6, No. 2, 01.01.1998, p. 103-108.

Research output: Contribution to journalArticle

Boeve, TJ, Reed, G, Carias De Oliveira, N, Titus, J, Janssens, S, Giugliano, RP, Torchiana, D, Daggett, W, Schwarz, R & Jang, IK 1998, 'Compdrison of argatroban and hirudin for the reperfusion of thrombotic arterial occlusion by tissue plasminogen activator', Journal of Thrombosis and Thrombolysis, vol. 6, no. 2, pp. 103-108. https://doi.org/10.1023/A:1008889202725
Boeve, Theodore J. ; Reed, Guy ; Carias De Oliveira, Nilto ; Titus, James ; Janssens, Stefan ; Giugliano, Robert P. ; Torchiana, David ; Daggett, Willard ; Schwarz, Richard ; Jang, Ik Kyung. / Compdrison of argatroban and hirudin for the reperfusion of thrombotic arterial occlusion by tissue plasminogen activator. In: Journal of Thrombosis and Thrombolysis. 1998 ; Vol. 6, No. 2. pp. 103-108.
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AU - Janssens, Stefan

AU - Giugliano, Robert P.

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