Copyright © 2002 by the European Society of Cardiology.
Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes
a Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.
b Duke Clinical Research Institute, Durham, NC, U.S.A.
c Texas Heart Institute, Houston, Texas, U.S.A.
d Ospedale Maggiore di Parma, Parma, Italy
e Scripps Research Institute, La Jolla, California, U.S.A.
f Katholieke Universiteit Gasthuisberg, Leuven, Belgium
revised October 30, 2001; accepted November 7, 2001
Abstract
Aims We compared the effects of hirudin and heparin on thrombin generation and activity among 350 patients with acute coronary syndromes enrolled in the GUSTO-IIb trial.
Methods and Results We obtained blood at baseline; at 4, 8, and 24h into infusion; at drug termination; and 6 and 24h after termination. We assayed for thrombin activity (fibrinopeptide A, activated protein C, thrombin–antithrombin complex), thrombin generation (prothrombin fragment 1·2), and platelet activation (platelet factor 4). Median baseline fibrinopeptide A and platelet factor 4 levels were elevated. Thrombin formation tended to increase with hirudin and decrease with heparin; by 8h into infusion, thrombin formation was significantly less for heparin (P<0·01). Most patients showed reduced thrombin activity and platelet activation during infusion of either agent. Hirudin-assigned patients had significantly lower fibrinopeptide A levels during infusion. Sixh post-termination, both groups had increased thrombin activity. Thrombin formation was increased in heparin patients (P<0·0001), significantly more than with hirudin (P=0·005). Higher values of haemostasis markers tended to be associated with poorer 30-day outcomes.
Conclusion Although hirudin did not prevent generation of new thrombin, it appeared to inhibit thrombin activity more than did heparin and produced slower increases in thrombin formation after discontinuation. The reelevation of thrombotic markers after stopping intravenous antithrombin therapy and the tendency toward increased thrombotic events with post-treatment increases in marker levels suggest an ongoing, clinically significant prothrombotic state. These results raise the possibility of improving on current antithrombotics by preventing thrombin generation and thrombin activity and by sustained suppression of the prothrombotic state. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.
Key Words: Acute coronary syndromes, prognosis, haemostasis, thrombin
f1 Correspondence: Kandice Kottke-Marchant, MD, PhD, Department of Clinical Pathology, L30, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A.
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