Rapid Activity of Platelet Inhibitor Drugs Study 2

50 consecutive patients with STEMI undergoing PPCI with bivalirudin (GP IIb/IIIa not allowed) will be randomized to receive Prasugrel (n= 25) or Ticagrelor (n= 25) before PPCI ( primary percutaneous coronary intervention) in a open label fashion. The loading dose of Prasugrel will be 60 mg, the loading dose of Ticagrelor will be 360 mg in 25 patients. The loading dose will be performed as soon as possible in the Emergency Room or in the Cath Lab. In the case of vomit in the first hour after drug loading dose a new reduced loading dose will be administered (30 mg Prasugrel or 180 mg Ticagrelor). All interventions will be performed by the femoral approach according to current standards. The use of thrombectomy before infarct-related artery stenting, of everolimus eluting stent and of closure devices will be strongly encouraged. Bivalirudin will be administered as a bolus 0.75 mg/kg followed by 1.75 mg/kg/h infusion during PCI. After PCI (percutaneous coronary intervention) a reduced bivalirudin infusion of 0.25 mg/kg/h for 4 hours will be allowed. Dual antiplatelet therapy (100 mg aspirin associated with 5 or 10 mg Prasugrel or 180 mg Ticagrelor) will be recommended for 12 months.

Residual platelet reactivity will be assessed in all patients at baseline (time of LD), and after 1, 2, 4 and 12 hours by a point-of-care test VerifyNow bedside available in the Intensive cardiac care Unit. High residual platelet reactivity will be defined as a Platelet Reactivity Units (PRU) > 240 by VerifyNow. At the same time point, Aspirin Reactivity Units (ARU) by VerifyNow will be also assessed. Follow-up will be performed by outpatient visits or telephone interviews at 6 months.

Inclusion criteria

• Patients presenting within 12 hours from the onset of symptoms with STEMI (ST segment elevation myocardial infarction)
• Informed, written consent

Exclusion criteria

• Age < 18 years or Age > 75 years
• Active bleeding; bleeding diathesis; coagulopathy
• Increased risk of bradycardiac events
• History of gastrointestinal or genitourinary bleeding <2 months
• Major surgery in the last 6 weeks
• History of intracranial bleeding or structural abnormalities
• Suspected aortic dissection
• Any previous TIA (transient ischemic attack)/stroke
• Any other condition that may put the patient at risk or influence study results or investigator's opinion (severe haemodynamic instability, known malignancies or other comorbid conditions with life expectancy <1 year)
• Administration in the week before the index event of clopidogrel, ticlopidine, prasugrel, ticagrelor, thrombolytics, bivalirudin, low-molecular weight heparin or fondaparinux .
• Concomitant oral or IV therapy with strong CYP3A inhibitors or strong CYP3A inducers, CYP3A with narrow therapeutic windows
• Known relevant hematological deviations: Hb <10 g/dl, Platelet count <100x10^9/l
• Use of coumadin derivatives within the last 7 days
• Chronic therapy with prasugrel or ticagrelor
• Known severe liver disease, severe renal failure
• Known allergy to the study medications