A critical appraisal of platelet glycoprotein IIb/IIIa inhibition.
J Am Coll Cardiol
; 36(7): 2028-35, 2000 Dec.
Article
em En
| MEDLINE
| ID: mdl-11127436
ABSTRACT
Despite the success of abciximab in preventing ischemic events after percutaneous coronary interventions, attempts to develop intravenous, small-molecule glycoprotein IIb/IIIa antagonists and diversify the clinical indications for these agents have produced varied results. The 30-day ischemic event reduction in the percutaneous coronary intervention trials has ranged by over three-fold (16% to 56%) and is greater among the acute coronary syndrome trials. The phase III trials exploring the role of oral glycoprotein IIb/IIIa inhibition have been consistently disappointing, with evolving evidence of increased mortality. Mechanisms contributing to these heterogeneous results may include normal variation in platelet or receptor number, differences in receptor activity, interpatient variation in pharmacological dose-response and the possibility of prothrombotic or nonglycoprotein IIb/IIIa effects. Plausibility of "suboptimal" effect is suggested by several recent studies. Trials investigating the role of intravenous small-molecule IIb/IIIa antagonists highlight the importance of effective dosing. The increase in bleeding and mortality observed in the oral glycoprotein IIb/IIIa studies indicate the consequences of suboptimal dosing on safety on one hand, while raising the possibility of important prothrombotic, counterregulatory or other sudden cardiac events. This article will undertake a review of the relevant platelet biology, discuss the mechanisms that may contribute to suboptimal antiplatelet efficacy with these agents and examine insights from the clinical trials supporting these concepts.
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Base de dados:
MEDLINE
Assunto principal:
Complexo Glicoproteico GPIIb-IIIa de Plaquetas
/
Doença das Coronárias
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
J Am Coll Cardiol
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos