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European Heart Journal 2002 23(21):1670-1677; doi:10.1053/euhj.2002.3191
Copyright © 2002 by the European Society of Cardiology.
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Continuous 48-h C1-inhibitor treatment, following reperfusion therapy, in patients with acute myocardial infarction

C. de Zwaana, A.H. Kleineb, J.H.C. Dirisb, J.F.C. Glatzc, H.J.J. Wellensa, P.F.W. Strengersd, M. Tissingd, C.E. Hackd, M.P. van Dieijen-Visserb and W.T. Hermensc,f1

a Department of Cardiology, University Hospital Maastricht, Maastricht, The Netherlands
b Department of Clinical Chemistry, University Hospital Maastricht, Maastricht, The Netherlands
d Central Laboratory of the Bloodtransfusion Service (CLB), Amsterdam, The Netherlands
c Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands

revised January 29, 2002; accepted February 7, 2002

Abstract

Aims Complement inhibition by C1-inhibitor has been shown to reduce myocardial ischaemia–reperfusion injury in animal models. We therefore studied the effects of intravenous C1-inhibitor, following reperfusion therapy, in patients with acute myocardial infarction.

Methods and Results C1-inhibitor therapy was started not earlier than 6h after acute myocardial infarction, in order to prevent interference with thrombolytic therapy. A loading dose of C1-inhibitor was followed by a continuous infusion for 48h, using three escalating dosage schemes. Efficacy of complement inhibition was estimated from C4 activation fragments. Plasma concentrations of myocardial proteins were compared to values measured in matched control patients. In 22 patients, C1-inhibitor was well tolerated and drug-related adverse events were not observed. Target plasma levels of C1-inhibitor were reached, with values of 48·2ml.kg–1 for distribution space and 35·5h for the half-life time of C1-inhibitor. A dose-dependent reduction of C4 fragments was found P=0·005). In 13 patients who received early thrombolytic therapy, release of troponin T and creatine kinase-MBmass was reduced by 36% and 57%P =0·001), compared to 18 controls.

Conclusion Continuous 48-h treatment with C1-inhibitor provides safe and effective inhibition of complement activation after reperfused acute myocardial infarction and may reduce myocardial injury.

Key Words: Complement inhibition, C1-inhibitor, myocardial infarction.

f1 Correspondence: Wim Th. Hermens, PhD, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

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