Abstract 3994: Pharmacodynamic Assessment of Platelet Inhibition by Prasugrel versus Clopidogrel in the TRITON-TIMI 38 Trial
TRITON-TIMI 38 randomized 13,608 ACS patients to prasugrel or standard dose clopidogrel, and demonstrated significantly reduced ischemic events with prasugrel. Prasugrel has been shown to produce higher and more consistent levels of platelet inhibition in healthy subjects, patients with stable CAD, and those undergoing elective PCI. Here we report a TRITON-TIMI 38 substudy examining the extent and consistency of platelet inhibition by prasugrel vs. clopidogrel in patients with ACS undergoing PCI. U.S. sites (n=13) prospectively enrolled TRITON-TIMI 38 patients to evaluate ADP-attenuated phosphorylation of platelet vasodilator stimulated phosphoprotein (VASP) (n=125) and, in a subset (n=31), ADP-stimulated platelet aggregation. Blood samples were collected pre-treatment, 1–2 h after PCI (≧1 h after loading dose), and at 30 days. VASP was measured by flow cytometry at a central core laboratory. Maximal platelet aggregation in response to 20 μM ADP was inhibited to a significantly greater extent in prasugrel- than in clopidogrel-treated patients at 1–2 h and 30 days (Fig A⇓). Results were similar with 5 μM ADP. VASP platelet reactivity index (PRI) was also significantly lower in prasugrel- than in clopidogrel-treated patients at both time points (Fig B⇓). Thienopyridine hyporesponsiveness, prespecified as <10% decrease in platelet aggregation and VASP PRI >50%, was less frequent in prasugrel- than in clopidogrel-treated patients. These results from TRITON-TIMI 38 support the hypothesis that greater and more consistent inhibition of ADP-mediated platelet function in ACS patients leads to a lower incidence of ischemic events.