Antithrombotic effects of ridogrel, a combined thromboxane A2 synthase inhibitor and prostaglandin endoperoxide-receptor antagonist, in a platelet- mediated coronary artery occlusion preparation in the dog

T. Yasuda, H. K. Gold, H. Yaotia, J. L. Guerrero, R. E. Holt, J. T. Fallon, R. C. Leinbach, D. Collen

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4 Scopus citations

Abstract

The comparative antithrombotic effects of aspirin and ridogrel, a combined thromboxane A2 synthase inhibitor and prostaglandin endoperoxide-receptor antagonist, were studied in a heparinized canine preparation consisting of an everted (inside-out) circumflex coronary artery segment that is highly thrombogenic and spontaneously occludes with platelet-rich thrombus. In five control dogs coronary artery occlusion occurred within 2 minutes (range, 1 to 4 minutes) and persisted during a 60-minute observation period. Aspirin, 17 mg/kg given orally 2 hours before the experiment, in seven dogs abolished arachidonic acid-induced platelet aggregation, prolonged the template bleeding time marginally to 4.6±1.4 minutes, and resulted in cyclic occlusion and reflow in all dogs (P=0.001 vs control by Fisher's exact test). Ridogrel, at a dose of 0.3 mg/kg intravenously over 10 minutes in six dogs, prolonged the template bleeding time from 3.8±1.2 minutes to 17±10 minutes and caused persistent patency in three dogs and cyclic occlusion and reflow in three dogs (P=0.002 vs control and P=0.07 vs aspirin). Ridogrel at a dose of 2.5 mg/kg over 10 minutes in five dogs prolonged the bleeding time from 3.3±1.7 minutes to 24±9.4 minutes, and was associated with persistent occlusion in one dog, reflow then reocclusion in one dog, and persistent patency in three dogs (P=0.05 vs control); ridogrel, 5 mg/kg, prolonged the bleeding time from 3±1 minutes to 28±4.5 minutes in five dogs and was associated with persistent patency in two dogs (P=0.008 vs control). The difference in patency between the combined high-dose ridogrel (2.5 or 5 mg/kg) and aspirin groups was also significant (P=0.03 by Fisher's exact test). It is concluded that, in this highly thrombogenic animal model, ridogrel is more potent for the prevention of platelet-mediated thrombosis than aspirin. Effective antithrombotic intervention is, however, associated with marked prolongation of the bleeding time.

Original languageEnglish
Pages (from-to)1103-1110
Number of pages8
JournalCoronary Artery Disease
Volume2
Issue number10
StatePublished - 1991
Externally publishedYes

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