Antiplatelet Therapy Effect on Extracellular Vesicles in Acute Myocardial Infarction

Study Overview
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Brief Summary
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Platelet activation and aggregation leads to myocardial infarction. Platelet P2Y12 receptors are essential for platelet activation. Antagonists against the P2Y12 receptor, which are established in secondary prevention of myocardial infarction, have unexplained anti-inflammatory effects. A novel P2Y12 receptor antagonist ticagrelor reduced infection-related mortality compared to clopidogrel, previous standard treatment for patients with myocardial infarction. Activated platelets release pro-inflammatory and procoagulant platelet extracellular vesicles. The investigators assume that decrease in infection-related mortality in patients treated with ticagrelor may be explained by greater inhibition of the release of platelet vesicles by ticagrelor, compared to clopidogrel. This study is expected to identify an additional mechanism of action of ticagrelor, which might contribute to the observed clinical benefits in patients treated with ticagrelor.

Official Title
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Antiplatelet Therapy Effect on Platelet Extracellular Vesicles in Acute Myocardial Infarction

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Informed consent to participate in the study Percutaneous coronary intervention with stent implantation due to first S T elevation myocardial infarction, or first non S T -elevation myocardial infarction Administration of a loading dose of clopidogrel Exclusion Criteria: Known coagulopathy Known history of bleeding disorder Suspicion of intracranial haemorrhage Need for oral anticoagulation therapy Administration of glycoprotein (GP) II b - III a antagonists Cardiogenic shock Severe chronic renal failure (estimated glomerular filtration rate < 30 mL/min) Severe liver insufficiency Chronic dyspnea Increased risk of bradycardia Autoimmune disease Infectious disease Neoplasms Pregnancy Study drug intolerance Co-administration of ticagrelor or clopidogrel with strong CYP3A4 inhibitors Participation in any previous study with ticagrelor or clopidogrel

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ticagrelor<br>Ticagrelor: oral, 180 mg once (loading dose) followed by 90 mg twice daily (maintenance dose) | Drug: Ticagrelor<br>* Comparison of ticagrelor with another antiplatelet drug (clopidogrel)<br>* Other names: Brilique;|
| Active Comparator: Clopidogrel<br>Clopidogrel: oral, 300 mg or 600 mg once (loading dose) followed by 75 mg once daily (maintenance dose) | Drug: Clopidogrel<br>* Comparison of clopidogrel with another antiplatelet drug (ticagrelor)<br>* Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Platelet Extracellular Vesicles/ml | Concentration of platelet extracellular vesicles/ml measured with flow cytometry | 6 months following the beginning of antiplatelet therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Extracellular Vesicles Exposing Fibrinogen | Concentration of extracellular vesicles exposing fibrinogen/ ml measured with flow cytometry | 6 months | 
| Concentration of Extracellular Vesicles Exposing Phosphatidylserine | Concentration of extracellular vesicles exposing phosphatidylserine/ml measured with flow cytometry | 6 months | 
| Concentration of Extracellular Vesicles From Endothelial Cells | The concentrations of extracellular vesicles from endothelial cells/ ml measured with flow cytometry | 6 months | 
| Concentration of Extracellular Vesicles From Leukocytes | Concentration of extracellular vesicles from leukocytes/ ml measured with flow cytometry | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extracellular vesicles, inflammation, thrombosis, antiplatelet drugs