Title: Pilot-study of combined administration of ridogrel and alteplase in patients with acute myocardial-infarction
Authors: Rapold, Hj
Van de Werf, Frans
Degeest, H
Arnout, Jozef
Sangtawesin, W
Vercammen, E
Declerck, F
Weber, C
Collen, Desire #
Issue Date: Jun-1991
Publisher: Current science
Series Title: Coronary artery disease vol:2 issue:4 pages:455-463
Abstract: The feasibility and pharmacodynamics of combined treatment with ridogrel, a thromboxane A2 synthase inhibitor and prostaglandin endoperoxide receptor antagonist, and alteplase (recombinant tissue-type plasminogen activator), were studied in 25 patients with acute myocardial infarction. In an unblinded, escalating dose protocol, the effects of heparin (group I, n = 8), and of 50 mg (group II, n = 3), 150 mg (group III, n = 3), 300 mg (group IV, n = 8), or 450 mg (group V, n = 3) of ridogrel, given as an intravenous bolus, each in combination with an infusion of 100 mg alteplase over 3 hours, were studied. Administration of ridogral and alteplase was not associated with major bleeding, although template bleeding times greater than 9 minutes were measured in nine patients. Coronary angiography, after 5 to 10 days, revealed a patent infarct-related vessel in all of 14 ridogrel-treated patients and in two of three control patients. The capacity of whole blood to generate thromboxane B2 decreased to 1% and 3%, respectively, of baseline (P < 0.001) at 45 minutes and 12 to 24 hours after administration of ridogrel (50 to 450 mg); it increased three-fold for 6-keto-prostaglandin F1-alpha and prostaglandin F2-alpha and 25-fold for prostaglandin E2 (P < 0.001). This is indicative of a protracted inhibition of thromboxane A2 synthase accompanied by a reorientation of prostaglandin endoperoxide metabolism toward platelet inhibitory prostanoids. In patients given 150 to 450 mg ridogrel, eight-fold more (4-mu-M) U46619 was required for 50% of maximal platelet aggregation, indicative for thromboxane A2-prostaglandin endoperoxide receptor antagonism. Thus, ridogrel is sufficiently safe and pharmacologically effective to warrant further clinical investigation of its potential as an adjuvant treatment to alteplase in patients with acute myocardial infarction.
ISSN: 0954-6928
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cardiology
Molecular and Vascular Biology
Biomedical Sciences Group Management - miscellaneous
# (joint) last author

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