Abstract 10247: Effects of Cangrelor in Prasugrel Treated Patients: A Pharmacodynamic In Vitro Investigation
Background: Cangrelor is an intravenous reversible fast-acting P2Y12 inhibitor. A therapeutic concentration of cangrelor in vitro before and after clopidogrel administration has potent P2Y12 inhibitory effects. Prasugrel is a more potent P2Y12 inhibitor than clopidogrel. However, if cangrelor can also exert rapid and further platelet inhibitory effects in prasugrel treated patients is unknown and represents the aim of this in vitro pharmacodynamic investigation.
Methods: Patients (n=60) on prasugrel 10mg maintenance therapy were included and randomized to receive either a 30mg or 60mg reload of prasugrel. Platelet reactivity was measured by whole blood vasodilator-stimulated phosphoprotein (VASP) and results reported in P2Y12 reactivity index (PRI). Platelet reactivity was measured with and without in vitro incubation of 500 nM of cangrelor at 3 time points: baseline, 1 hour and 4 hours after reload.
Results: Prasugrel reloading, in the absence of cangrelor, significantly reduced PRI after 1 and 4 hours with both 30mg and 60mg doses (p for trend for both groups = 0.001). In vitro cangrelor achieved significant reduction in PRI at baseline, while patients were on chronic maintenance prasugrel therapy (Figure). In patients reloaded with prasugrel 30mg, cangrelor significantly reduced PRI at 1 and 4 hours. In patients reloaded with prasugrel 60mg, cangrelor significantly reduced PRI at 1, but not at 4 hours (Figure). Prasugrel reloading in the presence of cangrelor also was associated with a reduction in PRI across time points with both 30mg (p for trend=0.008) and 60mg doses (p for trend= 0.001).
Conclusions: In patients on maintenance prasugrel therapy exposed to a re-loading dose regimen, in vitro cangrelor achieves potent and immediate antiplatelet effects. Similar levels of platelet reactivity were achieved only after 4 hours of a 60mg prasugrel reload, making intravenous cangrelor an attractive strategy if immediate antiplatelet effects are required.
- © 2013 by American Heart Association, Inc.