Daily Variability of Platelet Aggregation in Patients With Myocardial Infarction Treated With Prasugrel and Ticagrelor

Study Overview
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Brief Summary
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The aim of this study is to compare circadian variability of antiplatelet effect of prasugrel and ticagrelor maintenance doses during the initial days after acute myocardial infarction.

Detailed Description
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Prasugrel and ticagrelor are two oral P2Y12 receptor antagonists recommended as a part of dual antiplatelet therapy with aspirin in patients with acute myocardial infarction. Both drugs exert comparable antiplatelet effect following a loading dose. However, pharmacodynamic differences exist between these P2Y12 receptor inhibitors. Prasugrel is a prodrug that requires hepatic activation and permanently binds to platelet P2Y12 receptors, whereas ticagrelor is an active drug and blocks P2Y12 receptors reversibly. Another important difference is that prasugrel maintenance dose is administered once daily, while ticagrelor requires next dosage every 12 hours. These fundamental distinctions may affect the degree of platelet inhibition on maintenance doses during the first days after acute myocardial infarction.

Official Title
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Comparison of Circadian Variability of Platelet Inhibition in Patients With Myocardial Infarction Treated With Prasugrel and Ticagrelor

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Prasugrel
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: provision of informed consent prior to any study specific procedures diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment elevation myocardial infarction male or non-pregnant female, aged 18-75 years old provision of informed consent for angiography and percutaneous coronary intervention Exclusion Criteria: treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment hypersensitivity to ticagrelor or prasugrel contraindications for ticagrelor or prasugrel current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin active bleeding history of ischemic stroke or transient ischemic attack history of intracranial hemorrhage recent gastrointestinal bleeding (within 30 days) history of moderate or severe hepatic impairment history of major surgery or severe trauma (within 3 months) patient required dialysis manifest infection or inflammatory state concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment body weight below 60 kg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prasugrel<br>Patients with myocardial infarction will receive prasugrel as a part of dual antiplatelet therapy with aspirin. | Drug: Prasugrel<br>* Patients with myocardial infarction will receive a 60 mg prasugrel loading dose, followed by a maintenance dose of 10 mg once daily<br>* Other names: Efient;|
| Ticagrelor<br>Patients with myocardial infarction will receive ticagrelor as a part of dual antiplatelet therapy with aspirin. | Drug: Ticagrelor<br>* Patients with myocardial infarction will receive a 180 mg ticagrelor loading dose, followed by a maintenance dose of 90 mg twice daily<br>* Other names: Brilique;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circadian variability of platelet inhibition assessed with VASP | Platelet inhibition evaluated with VASP assay at 8:00, 12:00, 16:00 and 20:00 | Day 4 after acute myocardial infarction | 
| Circadian variability of platelet inhibition assessed with Multiplate | Platelet inhibition evaluated with Multiplate at 8:00, 12:00, 16:00 and 20:00 | Day 4 after acute myocardial infarction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High platelet reactivity at 8:00 assessed with VASP | Number of patients with high platelet reactivity evaluated with VASP assay at 8:00 | Day 4 after acute myocardial infarction | 
| High platelet reactivity at 12:00 assessed with VASP | Number of patients with high platelet reactivity evaluated with VASP assay at 12:00 | Day 4 after acute myocardial infarction | 
| High platelet reactivity 16:00 assessed with VASP | Number of patients with high platelet reactivity evaluated with VASP assay at 16:00 | Day 4 after acute myocardial infarction | 
| High platelet reactivity 20:00 assessed with VASP | Number of patients with high platelet reactivity evaluated with VASP assay at 20:00 | Day 4 after acute myocardial infarction | 
| High platelet reactivity 08:00 assessed with Multiplate | Number of patients with high platelet reactivity evaluated with Multiplate at 08:00 | Day 4 after acute myocardial infarction | 
| High platelet reactivity 12:00 assessed with Multiplate | Number of patients with high platelet reactivity evaluated with Multiplate at 12:00 | Day 4 after acute myocardial infarction | 
| High platelet reactivity 16:00 assessed with Multiplate | Number of patients with high platelet reactivity evaluated with Multiplate at 16:00 | Day 4 after acute myocardial infarction | 
| High platelet reactivity 20:00 assessed with Multiplate | Number of patients with high platelet reactivity evaluated with Multiplate at 20:00 | Day 4 after acute myocardial infarction | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prasugrel, ticagrelor, VASP, platelet reactivity, STEMI, NSTEMI