Coronary Artery Disease
Conditions
Keywords
antiplatelet effect, prasugrel, clopidogrel, stable angina
Brief summary
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.
Interventions
DRUGClopidogrel
Patient will be randomized to this intervention will receive in the first time the double dose of clopidogrel and after 15 days and 30 days we will control the responsivness of the study drug.
DRUGPrasugrel
Patient will be randomized to this intervention will receive in the first time prasugrel and after 15 days and 30 days we will control the responsivness of the study drug.
DRUGTicagrelor
Patient will be randomized to this intervention will receive in the first time Ticagrelor and after 14 days and 28 days we will change their therapy with the high clopidogrel dose or Prasugrel (dual crossover).
Sponsors
University of Roma La Sapienza
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| antiplatelet effect of standard dose of prasugrel or ticagrelor versus high dose clopidogrel in stable patients with high reactivity | 30 days | the antiplatelet effect in terms of level platelet reactivity (\< 450 Area under the curve (AU\*min)) of standard dose of Prasugrel (10 mg/day) either Ticagrelor (90 mg twice daily) versus high dose Clopidogrel (150 mg/day) in patients undergoing PCI with high reactivity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding (major, minor, or minimal) | 45 days | Bleeding (major, minor, or minimal) |
| Major Adverse Cardiac Cerebrovascular Events | 45 days | cardiovascular death, myocardial infarction, and stroke |
Countries
Italy
Outcome results
None listed