Comparison of platelet aggregation response in switching regimen from prasugrel to clopidogrel between CYP2C19 extensive versus non-extensive metabolizers

Little is known about the response of platelet aggregation in patients with acute coronary syndrome (ACS) when prasugrel is changed to clopidogrel. In this study, we evaluated the pharmacodynamic effects of this medication switch. Twenty-one consecutive ACS patients received prasugrel 20 mg as a loading dose before emergent percutaneous coronary intervention and 3.75 mg as a maintenance dose on days 2–7 (prasugrel phase). From day 8, prasugrel was switched to clopidogrel 75 mg/day (clopidogrel phase). P2Y12 reaction units (PRU) were measured 2–4 h after prasugrel loading, and on days 7, 11, 13, 15, and 42. Eight patients had the CYP2C19 extensive metabolizer (EM) genotype variant, while 13 were non-EM. In the EM group, no changes were observed in PRU level between days 7 and 15 (136.8 ± 51.2 vs. 166.2 ± 41.9, P = 0.07). However, in the non-EM group, a significant increase in PRU levels was observed between days 7 and 15 (165.8 ± 57.2 vs. 223.6 ± 60.9, P = 0.002). However, 2 patients in the non-EM group (15%) showed high on-clopidogrel treatment platelet reactivity (HTPR) 2–4 h after prasugrel loading, and during the clopidogrel phase there were significant differences in the incidence of HTPR between the EM and non-EM groups. Ischemic and bleeding events were not observed during this period. In the acute phase of ACS, changing from prasugrel to clopidogrel therapy decreased the effects of suppressing platelet aggregation. However, this change was not associated with increased ischemic or bleeding events.