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Variable inhibition of high-shear-induced platelet plug formation by eptifibatide and tirofiban under conditions of platelet activation and high von Willebrand release: a randomized, placebo-controlled, clinical trial.

Abstract：

BACKGROUND:Glycoprotein (GP) IIb/IIIa antagonists have become a mainstay for the treatment of acute coronary syndromes. Yet, they have rarely been evaluated under relevant pathophysiologic conditions, for example, high shear rates in the presence of physiologic calcium concentrations. We compared the efficacy of eptifibatide and tirofiban versus placebo on high shear-induced platelet plug formation in a model in which healthy subjects exhibit von Willebrand factor concentrations and platelet activation comparable to patients with acute coronary syndromes. METHODS:Thirty male volunteers received 2 ng/kg endotoxin and standard doses of eptifibatide, tirofiban, or placebo over a period of 5 hours in a randomized, double-blinded, placebo-controlled, double-dummy parallel-group trial. Platelet inhibition was measured with the Platelet Function Analyzer-100 (PFA-100) and the Ultegra method. RESULTS:Although bolus infusion of both GPIIb/IIIa antagonists inhibited high shear-induced platelet plug formation, continuous infusion of eptifibatide prolonged closure times more effectively than did tirofiban (P <.008). Interestingly, tirofiban had only placebo-like effects on platelet plug formation after 2 hours. However, when additional drug was exogenously added, closure time values were maximally prolonged in all cases. CONCLUSIONS:Standard doses, particularly of tirofiban, have limited impact on high shear-induced platelet plug formation at physiologic Ca(2+) concentrations.

journal_name

Am Heart J

journal_title

American heart journal

authors

Derhaschnig U,Pachinger C,Jilma B

doi

10.1016/j.ahj.2003.11.003

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

E17

issue

4

eissn

0002-8703

issn

1097-6744

pii

S000287030300766X

journal_volume

147

pub_type

临床试验,杂志文章,随机对照试验

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