Pharmacodynamic effects of cangrelor on platelet P2Y12 receptor-mediated signaling in prasugrel-treated patients.

Objectives The purpose of this study was to assess the in vitro P2Y 12 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 P2Y 12 receptor inhibition, particularly in high-risk settings. Cangrelor is a potent intravenous P2Y 12 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 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 P2Y 12 receptor inhibitory effects.