Eptifibatide provides additional platelet inhibition in Non–ST-Elevation myocardial infarction patients already treated with aspirin and clopidogrel: Results of the platelet activity extinction

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• 作者：Miles Dalby ; Gilles Montalescot ; Claire Bal dit Sollier ; Eric Vicaut ; Thierry Soulat ; Jean-Philippe Collet ; Ré ; mi Choussat ; Vanessa Gallois ; Gé ; rard Drobinski ; Ludovic Drouet ; Daniel Thomas
• 关键词：AHA Scientific Statements ; prevention ; women ; cardiovascular diseases ; risk factors
• 刊名：Journal of the American College of Cardiology
• 出版年：2004
• 出版时间：21 January 2004
• 年：2004
• 卷：43
• 期：2
• 页码：162-168
• 全文大小：207 K

文摘

The present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non–ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention.

Background

Although thienopyridines and glycoprotein (GP) IIb/IIIa antagonists are often co-prescribed in the context of NSTEMI, the antiplatelet interaction of these agents is poorly described and the superiority of GP IIb/IIIa antagonists above thienopyridine treatment alone is not clear.

Methods

Thirty-two NSTEMI patients treated with aspirin and enoxaparin were studied using flow cytometry to define parameters of platelet activation with a panel of agonists before clopidogrel, after clopidogrel, and during an eptifibatide infusion following the clopidogrel load.

Results

After platelet activation with adenosine diphosphate, thrombin receptor-activating peptide, or U46-619, relative reductions in conformationally activated GP IIb/IIIa receptor expression (evaluated with PAC-1) of 48 % , 43 % , and 33 % , respectively (all p < 0.0001), were seen with clopidogrel, but further 80 % , 78 % , and 72 % (all p < 0.0001) reductions were seen with eptifibatide. With the same agonists, fibrinogen binding was significantly reduced after clopidogrel by 70 % , 64 % , and 81 % (all p < 0.0001) and again further reduced with eptifibatide by 90 % , 95 % , and 69 % (all p < 0.0001). The total number of GP IIb/IIIa receptors (measured as P2 expression) and P-selectin expression fell after clopidogrel, after ex vivo stimulation with the same agonists; however, both parameters increased slightly during the eptifibatide infusion.

Conclusions

The activated GP IIb/IIIa expression and fibrinogen binding findings indicate that eptifibatide provides significant potent antiplatelet activity above aspirin and clopidogrel, suggesting additive immediate protection in the treatment of NSTEMI. The P2 and P-selectin findings suggest the possibility of a partial agonist and/or pro-inflammatory effect.