Pharmacodynamic Effects of Cangrelor on聽Platelet P2Y₁₂ Receptor-Mediated Signaling in Prasugrel-Treated Patients

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• 作者：Fabiana Rollini ; MD ; Francesco Franchi ; MD ; Antonio Tello-Montoliu ; MD ; PhD ; Ronakkumar Patel ; MD ; Andrew Darlington ; MD ; José ; Luis Ferreiro ; MD ; Jung Rae Cho ; MD ; Ana Muñ ; iz-Lozano ; MD ; Bhaloo Desai ; PhD ; Martin M. Zenni ; MD ; Luis A. Guzman ; MD ; Theodore A. Bass ; MD ; Dominick J. Angiolillo ; MD ; PhD ; ^{dominick.angiolillo@jax.ufl.edu" class="auth_mail}
• 关键词：cangrelor ; platelet reactivity ; prasugrel
• 刊名：JACC: Cardiovascular Interventions
• 出版年：April, 2014
• 年：2014
• 卷：7
• 期：4
• 页码：426-434
• 全文大小：868 K

文摘

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Objectives

The purpose of this study was to assess the in vitro P2Y₁₂ receptor inhibitory effects of cangrelor on platelets from patients on maintenance prasugrel therapy treated with 2 reloading dose regimens.

Background

Despite its more potent and rapid antiplatelet effects compared with clopidogrel, recent studies have shown variability in prasugrel-mediated P2Y₁₂ receptor inhibition, particularly in high-risk settings. Cangrelor is a potent intravenous P2Y₁₂ receptor inhibitor.

Methods

A total of 60 patients with coronary artery disease on maintenance prasugrel (10 mg/day) therapy were randomized to a 30- or 60-mg reload of prasugrel. The platelet reactivity index (PRI), as assessed by whole-blood vasodilator-stimulated phosphoprotein, was measured with and without in vitro incubation of cangrelor (500 nM) at baseline, and at 1 and 4 h after reload.

Results

In the absence of cangrelor, prasugrel reloading reduced PRI (p < 0.001 for both doses), although a 60-mg reload had greater platelet inhibition compared with a 30-mg reload at 4 h (p聽=聽0.001). Cangrelor was associated with a reduction in PRI values during the overall study time course in patients reloaded with 30 mg (p聽= 0.001) and 60 mg (p < 0.001) of prasugrel. In patients reloaded with 30 mg prasugrel, cangrelor decreased PRI at each time point (baseline, p < 0.001; 1 h, p聽= 0.013; 4 h, p聽= 0.001). In patients reloaded with 60 mg prasugrel, cangrelor decreased PRI at baseline (p < 0.001) and 1 h (p聽= 0.002); levels of platelet reactivity comparable to those achieved with cangrelor were observed only at 4 h (p聽= 0.325). The intergroup comparisons with cangrelor were not significant at any time point.

Conclusions

In patients on maintenance prasugrel therapy exposed to a reloading dose (30 or 60 mg) of prasugrel, in vitro cangrelor is associated with further platelet P2Y₁₂ receptor inhibitory effects.