High and low on-treatment platelet reactivity to P2Y12 inhibitors in a contemporary cohort of acute coronary syndrome patients undergoing percutaneous coronary intervention

Introduction: There is compelling evidence supporting the association between high on-treatment platelet reactivity (HPR) and low on-treatment platelet reactivity (LPR) to clopidogrel with atherothrombotic and bleeding events, respectively. However, it is uncertain if current cutoff values should be used in prasugrel- or ticagrel-or-treated subjects. The objective of this analysis was to evaluate the pharmacodynamic (PD) efficacy of P2Y(12) antagonists in a contemporary real-world population. Materials and methods: This PD study included 988 patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) and receiving dual therapy with aspirin and a P2Y(12) inhibitor (clopidogrel, prasugrel or ticagrelor). Platelet function was assessed at day 1 and day 30 post-PCI by VerifyNow P2Y(12) assay, multiple electrode aggregometry and vasodilator-stimulated phosphoprotein (VASP) assay. Results: Clopidogrel-treated patients (n=324) had greater platelet reactivity than those receiving ticagrel- or (n=469) or prasugrel (n=195) at both time points (p<0.001 for all comparisons). No difference between ticagrelor and prasugrel was observed at day 1 with the VerifyNow P2Y(12) assay (51.5 +/- 2.8 vs. 42.7 +/- 3.5 PRUs; p=0.298), whereas ticagrelor achieved greater platelet inhibition at day 30 (48.1 +/- 2.5 vs. 89.2 +/- 4.2 PRUs; p<0.001). Similar results were obtained with the VASP assay. Both prasugrel and ticagrelor had markedly lower HPR rates than clopidogrel and very high rates of LPR at both time points. Conclusions: Prasugrel and ticagrelor displayed more potent and consistent PD effects than clopidogrel in ACS patients undergoing PCI, with a trend towards greater platelet inhibition with ticagrelor during the maintenance phase of therapy compared to prasugrel.