• To evaluate the use of a prasugrel 60 mg loading dose (LD) administered during percutaneous coronary intervention (PCI) with and without a prior LD of clopidogrel on platelet inhibition in patients presenting with acute coronary syndrome (ACS).
• Platelet inhibition following a prasugrel LD in clopidogrel pretreated patients was determined in a time-dependent manner for two different prasugrel loading doses (30 mg and 60 mg).
• To provide understanding of the effects of this combination on platelet inhibition to physicians for the use of prasugrel in patients who have already been pre-treated with clopidogrel.

• Randomized, double-blind, double-dummy, 3-arm, parallel, active-comparator controlled study performed at 36 sites in 8 countries
• Designed to evaluate the pharmacodynamic response in ACS patients who are likely to undergo PCI using 3 different strategies: placebo plus prasugrel 60 mg LD, clopidogrel 600 mg LD plus prasugrel 60 mg LD, or clopidogrel 600 mg LD plus prasugrel 30 mg LD
• 282 patients were randomized
• The primary end point for this study was the VN-reported PRU, measured 6 hours after prasugrel LD
• Platelet function was assessed using VerifyNow P2Y12 Reaction Units (PRU) immediately before prasugrel LD, and 2, 6, 24, and 72 hours after prasugrel LD

• High risk of bleeding
• Previous history of transient ischemic attack or stroke.

• 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)

Secondary Endpoint:

• 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.