Abstract 16420: Impact of Potent Oral P2Y12 Inhibiting Therapies on Multiple Platelet Signaling Pathways: Results of a Prospective Ex vivo Pharmacodynamic Investigation

Background: Although pharmacodynamic (PD) studies have compared the effects of the P2Y 12 receptor inhibitors prasugrel and ticagrelor on adenosine (ADP) mediated platelet aggregation showing enhanced effects compared with clopidogrel, to date there are no studies assessing how these agents affect other platelet signaling pathways. The aim of this study was to assess the PD effects on multiple platelet signaling pathways after switching clopidogrel treated patients to prasugrel or ticagrelor. Methods: In this prospective PD study, clopidogrel (75mg/qd) treated patients (n=110) with coronary artery disease (CAD) were randomized to switch to prasugrel (60mg loading dose/10mg maintenance dose qd) or ticagrelor (180mg loading dose /90mg maintenance dose bid) for 1 week. PD assessments were performed to evaluate the acute (baseline and 30 min, 2 hrs, 24 hrs after LD) and chronic (1 week) effects of therapy using Multiple Electrode Aggregometry following stimuli with multiple agonists: arachidonic acid (AA), ADP (with and without PGE 1 ), collagen and TRAP. Results: There were no differences in baseline (on-clopidogrel) platelet reactivity. Switching to prasugrel and ticagrelor led to a reduction in platelet reactivity stimulated by ADP (with and without PGE 1 ) as early as 30 min and sustained up to 1 week (p 12 inhibition. No PD differences were found between prasugrel and ticagrelor with all agonists. Conclusions: In CAD patients on maintenance clopidogrel therapy, in addition to exerting prompt and enhanced inhibition of ADP mediated platelet aggregation, switching to either prasugrel or ticagrelor is also associated with diminished thrombin-induced platelet aggregation. These ex vivo results support an interplay between the ADP P2Y 12 and the thrombin platelet signaling pathways previously reported in in vitro experimental models.