Copyright © 1999 by the European Society of Cardiology.
Anticoagulant properties, clinical efficacy and safety of efegatran, a direct thrombin inhibitor, in patients with unstable angina
Department of Cardiology, Rotterdam Heart Centre, Division Thoraxcentre
Division of Haemostasis, Department of Haematology, University Hospital Dijkzigt, Erasmus University Rotterdam, Rotterdam
Cardialysis B.V. Rotterdam
Medisch Centrum Alkmaar, Alkmaar
Spaarne Ziekenhuis, Heemstede, Medisch Spectrum Twente, Enschede, The Netherlands
revised December 15, 1998; accepted December 16, 1998 1998
Abstract
Aims Thrombin plays a key role in the clinical syndrome of unstable angina. We investigated the safety and efficacy of five dose levels of efegatran sulphate, a direct thrombin inhibitor, compared to heparin in patients with unstable angina.
Methods Four hundred and thirty-two patients with unstable angina were enrolled. Five dose levels of efegatran were studied sequentially, ranging from 0·105mg.kg–1.h–1to 1·2mg.kg–1.h–1over 48h. Safety was assessed clinically, with reference to bleeding and by measuring clinical laboratory parameters. Efficacy was assessed by the number of patients experiencing any episode of recurrent ischaemia as measured by computer-assisted continuous ECG ischaemia monitoring. Clinical end-points were: episodes of recurrent angina, myocardial infarction, coronary intervention (PTCA or CABG), and death.
Results Efegatran demonstrated dose dependent ex-vivo anticoagulant activity with the highest dose level of 1·2mg.kg–1.h–1resulting in steady state mean activated partial thromboplastin time values of approximately three times baseline. Thrombin time was also increased. Neither of the efegatran doses studied were able to suppress myocardial ischaemia during continuous ECG ischaemia monitoring to a greater extent than that seen with heparin. There were no statistically significant differences in clinical outcome or major bleeding between the efegatran and heparin groups. Minor bleeding and thrombophlebitis occurred more frequently in the efegatran treated patients.
Conclusion Administration of efegatran sulphate at levels of at least 0·63mg.kg–1.h–1provided an anti-thrombotic effect which is at least comparable to an activated partial thromboplastin time adjusted heparin infusion. There was no excess of major bleeding. The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin. Thus, like other thrombin inhibitors, efegatran sulphate is easier to administer than heparin. However, no clinical benefits of efegatran over heparin were apparent.
Key Words: Anti-thrombin, efegatran, unstable angina, ECG ischaemia monitoring
f1 Correspondence: A. P. J. Klootwijk, MD, Erasmus University Rotterdam, University Hospital Dijkzigt, Rotterdam Heart Centre, Division Thoraxcentre H 304, P.O. Box 2040, NL-3000 CA Rotterdam, The Netherlands.
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