The use of dual antiplatelet therapy is considered standard of care in patients post percutaneous coronary intervention (PCI) with stenting. However, a significant proportion of patients is considered clopidogrel resistant and this resistance is shown to be accompanied by future adverse events. The aim of the study is to define in consecutive patients with acute coronary syndrome (ACS) undergoing PCI, those aged>75years and/or weighted<60 Kg with high on-clopidogrel platelet reactivity (Platelet Reactivity Units-PRU≥235) as estimated 24 hours post PCI with the VerifyNow assay. Those patients will be randomized after informed concent in 1:1 fashion to prasugrel 5 mg or clopidogrel 150mg daily. Platelet reactivity will be assessed at day 15 and then treatment crossover will be performed. At day 30 platelet reactivity will be determined as well.

Inclusion Criteria:

1. Age ≥18 years old

2. Patients having PCI with stenting 24 hours prior randomization, meeting the following criteria :

   • Acute coronary syndrome (unstable angina or myocardial infarction)
   • TIMI risk score>2

3. Platelet reactivity in PRU ≥235 24 hours post-PCI

4. Age≥75 years and/or weight<60 Kg

4. Informed consent obtained in writing

Exclusion Criteria:

• A history of bleeding diathesis
• Chronic oral anticoagulation treatment
• Contraindications to antiplatelet therapy
• Known platelet function disorders
• PCI or coronary artery bypass surgery < 3 months
• Unsuccessful PCI (residual stenosis > 30% or flow < Thrombolysis in myocardial infarction flow 3)
• Planned staged PCI in the next 30 days
• Hemodynamic instability
• hemodialysis
• Creatinine clearance <25 ml/min
• inability to give informed consent
• High likelihood of being unavailable for the Day 30
• History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 6 months.
• Other bleeding diathesis, or considered by investigator to be at high risk for bleeding on longterm antiplatelet therapy.
• Any previous history of ischemic stroke, transient ischemic attack, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
• Thrombocytopenia (<100.000 / μL) at randomization
• Anaemia (Hct <30%) at randomization
• Polycythaemia (Hct > 52%) at randomization
• Periprocedural IIb/IIIa inhibitor administration