(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
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