The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting

OBJECTIVES: We determined the effect of clopidogrel dosing on the incidence of nonresponsiveness (NR) and high post-treatment platelet aggregation (post-PA). BACKGROUND: We have reported NR after a 300-mg loading dose. Limited information is available on the comparative effect of a 600-mg loading dose on the incidence of NR and high post-PA. METHODS: Clopidogrel responsiveness and post-PA were measured in patients undergoing stenting (n = 190) randomly treated with either a 300-mg or a 600-mg clopidogrel load. Nonresponsiveness was defined as <10% absolute change in platelet aggregation, and high post-PA was defined as >75th percentile aggregation after 300 mg clopidogrel. RESULTS: Nonresponsiveness was lower after 600 mg compared to the 300-mg dose (8% vs. 28% and 8% vs. 32% with 5 and 20 μM ADP, respectively, p < 0.001). Among the patients with high post-PA after 300 mg clopidogrel, 62% to 65% had NR, whereas after the 600-mg dose, all of the patients with high post-PA had NR. CONCLUSIONS: A 600-mg clopidogrel loading dose reduces the incidence of NR and high post-PA as compared to a 300-mg dose. Higher dosing strategies and methods to confirm platelet inhibition should be further investigated in order to optimally use clopidogrel in patients undergoing stenting.