Oral glycoprotein IIb/IIIa antagonism in patients with coronary artery disease

Bianca Rocca, F Catella Lawson, S Kapoor, D Moretti, S De Marco, Gj Vigilante, Aj Cucchiara, Ke Ramsey, S Combe, P Theroux, Ga Fitzgerald

Risultato della ricerca: Contributo in rivistaArticolo in rivista

6 Citazioni (Scopus)

Abstract

Dose-finding studies and trials of interaction of oral glycoprotein IIb/IIIa antagonists with other antiplatelet agents have been limited. We hypothesized that these detailed assessments could be first performed in patients with stable coronary artery disease (CAD) and then extrapolated to the target population. To this end, we performed 2 sequential studies. The first study examined the dose-related effects on indexes of platelet and vascular function induced by the oral inhibitor RPR 109891, when given alone and in combination with aspirin, in patients (n = 100) with stable CAD. The second study (the Antagonism of the FIbrinogen Receptor after Myocardial Events trial) assessed the pharmacodynamics and safety of derived regimens in patients (n = 320) with unstable coronary syndromes. In patients with stable CAD, platelet aggregation was dose dependently inhibited by RPR 109891, and the dose-response relation was shifted to the right by the concomitant administration of aspirin (p = 0.0001). The degree of platelet inhibition induced by 3 doses of RPR 109891 (plus aspirin) was lower in patients with unstable than stable CAD. No drug-related major bleeding occurred in either study. RPR 109891 treatment was associated with acute and delayed thrombocytopenia. In conclusion, chronic treatment with an oral glycoprotein IIb/IIIa antagonist (1) induces antiplatelet effects that are potentiated by concomitant administration of aspirin, (2) may require dose adjustment in syndromes of platelet activation, (3) is associated with a low rate of clinically significant bleeding when doses inducing incomplete inhibition of platelet aggregation are used, and (4) requires frequent monitoring of platelet count unless reliable predictors of delayed thrombocytopenia become available.
Lingua originaleEnglish
pagine (da-a)236-242
Numero di pagine7
RivistaTHE AMERICAN JOURNAL OF CARDIOLOGY
Volume88
Stato di pubblicazionePubblicato - 2001

Keywords

  • Administration, Oral
  • Adult
  • Aged
  • Aspirin
  • Coronary Disease
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Humans
  • Middle Aged
  • Peptides
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Thrombocytopenia
  • Thromboxane B2

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