| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1996;94:2389-2395.)
© 1996 American Heart Association, Inc.
Articles |
Distinct Effects of Recombinant Desulfatohirudin (Revasc) and Heparin on Plasma Levels of Fibrinopeptide A and Prothrombin Fragment F1.2 in Unstable Angina
A Multicenter Trial
the Sol Sherry Thrombosis Research Center, Department of Medicine, Temple University School of Medicine, Philadelphia, Pa; the Mayo Clinic, Rochester, Minn; Massachusetts General Hospital, Boston; Duke University Medical Center, Durham, NC; CIBA-Geigy, Summit, NJ; and the Cleveland (Ohio) Clinic.
Background Thrombin plays an important role in the pathogenesis of acute coronary thrombosis. We studied the effects of a direct thrombin inhibitor, recombinant desulfatohirudin, and heparin on plasma levels (at 0, 4, 12, and 24 hours) of fibrinopeptide A (FPA), which reflects thrombin action, and prothrombin fragment F1.2, which reflects thrombin generation, in patients with unstable angina.
Methods and Results Patients were randomized to one of two doses of heparin (n=50) (target activated partial thromboplastin time, 65 to 90 seconds or 90 to 110 seconds) or one of four doses of r-hirudin (n=113) (0.05, 0.10, 0.20, or 0.30 mg·kg-1·h-1 by infusion). r-Hirudin induced a dose-dependent decline in plasma FPA. At 24 hours, FPA levels with 0.1- to 0.3-mg·kg-1·h-1 r-hirudin regimens were significantly lower than with 0.05 mg·kg-1·h-1 r-hirudin; levels with 0.1- to 0.2-mg·kg-1·h-1 r-hirudin regimens were lower than with both heparin regimens. Plasma F1.2 did not decline significantly during therapy with heparin or hirudin except at 0.3 mg·kg-1·h-1 hirudin. At 24 hours, they were higher with the 0.05-mg·kg-1·h-1 r-hirudin regimen than with other regimens. For comparable levels of thrombin generation (F1.2 levels), FPA levels were higher in heparin patients than in hirudin patients. For the same FPA values, the corresponding F1.2 values were higher in the hirudin group.
Conclusions Our findings provide evidence for distinct in vivo effects of the two agents and suggest that r-hirudin is a relatively more potent inhibitor of thrombin action but a less effective inhibitor of thrombin generation than heparin. The lower FPA levels in hirudin patients may reflect its ability to inactivate clot-bound thrombin. The relative clinical efficacies of the two agents need to be defined by clinical trials in progress.
Key Words: angina • coagulation • anticoagulants • hirudin • heparin
This article has been cited by other articles:
 |
|
 |
|
  M. Tobu, O. Iqbal, D. Hoppensteadt, B. Neville, H. L. Messmore, and J. Fareed Anti-Xa and Anti-IIa Drugs Alter International Normalized Ratio Measurements: Potential Problems in the Monitoring of Oral Anticoagulants Clinical and Applied Thrombosis/Hemostasis, October 1, 2004; 10(4): 301 - 309. [Abstract] [PDF]
|
|
|
|
 |
|
 J.W. Eikelboom, J.I. Weitz, A. Budaj, F. Zhao, I. Copland, P. Maciejewski, M. Johnston, and S. Yusuf Clopidogrel does not suppress blood markers of coagulation activation in aspirin-treated patients with non-ST-elevation acute coronary syndromes Eur. Heart J., November 2, 2002; 23(22): 1771 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kottke-Marchant, M.C. Bahit, C.B. Granger, P. Zoldhelyi, D. Ardissino, L. Brooks, J.H. Griffin, R.F. Potthoff, F. Van de Werf, R.M. Califf, et al. Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes Eur. Heart J., August 1, 2002; 23(15): 1202 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Oldgren, R. Linder, L. Grip, A. Siegbahn, and L. Wallentin Coagulation Activity and Clinical Outcome in Unstable Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 1059 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.D Flather, J.I Weitz, S Yusuf, J Pogue, B Sussex, J Campeau, J Gill, R Schuld, C.D Joyner, A.L Morris, et al. Reactivation of coagulation after stopping infusions of recombinant hirudin and unfractionated heparin in unstable angina and myocardial infarction without ST elevation: results of a randomized trial Eur. Heart J., September 1, 2000; 21(17): 1473 - 1481. [Abstract] [PDF]
|
|
|
|
|
|
P. A. Merlini, D. Ardissino, R. D. Rosenberg, E. Colombi, P. Agricola, L. Oltrona, F. Ottani, M. Galvani, K. A. Bauer, B. Bottasso, et al. In Vivo Thrombin Generation and Activity During and After Intravenous Infusion of Heparin or Recombinant Hirudin in Patients With Unstable Angina Pectoris Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2162 - 2166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pernerstorfer, U. Hollenstein, J.-B. Hansen, P. Stohlawetz, H.-G. Eichler, S. Handler, W. Speiser, and B. Jilma Lepirudin blunts endotoxin-induced coagulation activation Blood, March 1, 2000; 95(5): 1729 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Antman, M. Cohen, D. Radley, C. McCabe, J. Rush, J. Premmereur, and E. Braunwald Assessment of the Treatment Effect of Enoxaparin for Unstable Angina/Non-Q-Wave Myocardial Infarction : TIMI 11B-ESSENCE Meta-Analysis Circulation, October 12, 1999; 100(15): 1602 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Linder, J. Oldgren, N. Egberg, L. Grip, G. Larson, A. Siegbahn, and L. Wallentin The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease Eur. Heart J., April 1, 1999; 20(7): 506 - 518. [Abstract] [PDF]
|
|
|
|
|
|
J. I. Weitz, E. Young, M. Johnston, A. R. Stafford, J. C. Fredenburgh, and J. Hirsh Vasoflux, a New Anticoagulant With a Novel Mechanism of Action Circulation, February 9, 1999; 99(5): 682 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Altman Controversies in Antithrombotic Therapy in Cardiovascular Diseases Clinical and Applied Thrombosis/Hemostasis, January 1, 1998; 4(1): 11 - 24. [Abstract] [PDF]
|
|