Effect on Platelet Reactivity From a Prasugrel Loading Dose After a Clopidogrel Loading Dose Compared With a Prasugrel Loading Dose Alone

BACKGROUND: Adding a prasugrel loading dose (LD) to a clopidogrel LD could be desirable because clopidogrel may fail to provide adequate levels of platelet inhibition in patients with acute coronary syndrome undergoing percutaneous coronary intervention. METHODS AND RESULTS: The pharmacodynamic response of prasugrel 60 mg ld alone was compared with prasugrel 60 mg or 30 mg added 24 hours to clopidogrel 600 mg in Transferring From Clopidogrel Loading Dose To Prasugrel Loading Dose In Acute Coronary Syndrome Patients study: a multicenter, randomized, double-blind, double-dummy, 3-arm, parallel, active-comparator controlled study. Two hundred eighty-two patients were randomized to 3 LD strategies: placebo plus prasugrel 60 mg, clopidogrel 600 mg plus prasugrel 60 mg, or clopidogrel 600 mg plus prasugrel 30 mg. Platelet function was assessed using VerifyNow P2Y12 Reaction Units (PRU) immediately before prasugrel LD, and 2, 6, 24, and 72 hours after prasugrel LD in 149 patients with evaluable platelet function studies. At 6 hours after the prasugrel 60 mg LD, the least squares mean (95% confidence interval) difference between placebo/prasugrel 60 mg and clopidogrel 600 mg/prasugrel 60 mg (primary outcome) was 22.2 (-11.0 to 55.5; P=0.19; least squares mean PRU 57.9 versus 35.6, respectively). For clopidogrel 600 mg/prasugrel 30 mg (least squares mean PRU, 53.9), the difference was 3.9 (-28.2 to 36.1; P=0.81) versus placebo/prasugrel 60 mg. No significant differences in PRU were observed at any time point across the 3 groups. There were few bleeding events observed regardless of treatment. CONCLUSIONS: Platelet reactivity with prasugrel 60 mg LD added to clopidogrel 600 mg LD was not significantly different compared with prasugrel 60 mg LD alone in acute coronary syndrome patients undergoing percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01115738.