High Clopidogrel Dose Versus Prasugrel and Ticagrelor in High Reactive Stable Patients

Comparison of Therapy With TICAGRELOR, Prasugrel and High Clopidogrel Dose in PCI Patients With High on Treatment Platelet Reactivity and Genotype Variation

Dual antiplatelet therapy with Aspirin and Clopidogrel for at least one year is essential in patients following an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) with drug eluting stent(s) implantation. Interindividual variability in platelet response to Clopidogrel has been reported, with several mechanisms (intrinsic high platelet reactivity [PR], variability of the drug metabolism, and various drug interactions) being implicated for high post-Clopidogrel treatment PR. The investigators aim to perform a prospective, single-center, investigator-initiated, randomized, study to compare platelet inhibition by Prasugrel 10 mg/day, Ticagrelor (90 mg twice daily) and high-dose 150 mg/day Clopidogrel in patients with High on-treatment platelet reactivity (HTPR) with standard dose of Clopidogrel. Patients with HTPR (defined as area under curve-AUC ≥ 450 or > 45 Unit) and with loss-of-function allele CYP2C19*2 will be enrolled in the study and will be randomized (Day 0) in a 1:1:1 ratio, to either Clopidogrel 150 mg a day or Prasugrel 10 mg a day or Ticagrelor (90 mg twice daily) until Day-15 and-30 post randomization.

Inclusion Criteria:

• patients underwent to percutaneous coronary intervention (PCI)
• clopidogrel resistance after Platelet reactivity blood test

Exclusion Criteria:

• history of bleeding diathesis
• chronic oral anticoagulation treatment
• contraindications to antiplatelet therapy
• PCI or coronary artery bypass grafting (CABG) < 3 months
• hemodynamic instability
• platelet count < 100,000/μl
• hematocrit < 30%
• creatinine clearance < 25 ml/min
• Patients with a history of stroke
• contraindication for prasugrel administration
• patients weighing < 60 kg
• > 75 years of age.