Pharmacodynamic Effects of Cangrelor on Platelet P2Y12 Receptor–Mediated Signaling in Prasugrel-Treated Patients
What are the in vitro P2Y12 receptor inhibitory effects of cangrelor on platelets from patients on maintenance prasugrel therapy treated with two reloading dose regimens?
The authors randomized 60 patients with coronary artery disease on maintenance prasugrel (10 mg/day) therapy 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 hours after reload.
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 hours (p = 0.001). Cangrelor was associated with a reduction in PRI values during the overall study time course in patients reloaded with 30 mg (p = 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 hour, p = 0.013; 4 hours, p = 0.001). In patients reloaded with 60 mg prasugrel, cangrelor decreased PRI at baseline (p < 0.001) and 1 hour (p = 0.002), but comparable levels of platelet reactivity were observed at 4 hours (p = 0.325).
In patients on maintenance prasugrel therapy and reloaded with (30 or 60 mg) of prasugrel, in vitro cangrelor is associated with further platelet P2Y12 receptor inhibitory effects.
The results of this study suggest that administration of cangrelor would likely be associated with further platelet inhibition in patients who are already on prasugrel. Similar findings have been observed in patients on ticagrelor (Schneider J, et al. JACC Cardiovasc Interv 2014;Mar 19:[Epub ahead of print]). These results should not be surprising since the oral agents are dosed for chronic platelet inhibition and have a slightly lower antiplatelet effect (and less bleeding risk) compared with parenteral therapy dosed for periprocedural efficacy. The clinical significance of these studies is unclear, and the role for more potent antiplatelet therapy in patients who are already on prasugrel or ticagrelor needs to be defined in a randomized controlled trial.
Keywords: Coronary Artery Disease, Microfilament Proteins, Platelet Aggregation Inhibitors, Thiophenes, Phosphoproteins, Piperazines, Blood Platelets, Cell Adhesion Molecules, Angioplasty, Balloon, Coronary, Purinergic P2Y Receptor Antagonists
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