Antiplatelet Therapy Effect on Extracellular Vesicles in Acute Myocardial Infarction

Medical University of Warsaw60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Myocardial Infarction

Interventions

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (2)

Laboratory of Experimental Clinical Chemistry, Academic Medical Centre of the University of Amsterdam

Amsterdam, Netherlands

1st Chair and Department of Cardiology, Medical University of Warsaw

Warsaw, Poland

Outcomes

Primary Outcomes

Concentration of Platelet Extracellular Vesicles/ml

Concentration of platelet extracellular vesicles/ml measured with flow cytometry

Time frame: 6 months following the beginning of antiplatelet therapy

Secondary Outcomes

Concentration of Extracellular Vesicles Exposing Fibrinogen

Concentration of extracellular vesicles exposing fibrinogen/ ml measured with flow cytometry

Time frame: 6 months

Concentration of Extracellular Vesicles Exposing Phosphatidylserine

Concentration of extracellular vesicles exposing phosphatidylserine/ml measured with flow cytometry

Time frame: 6 months

Concentration of Extracellular Vesicles From Endothelial Cells

The concentrations of extracellular vesicles from endothelial cells/ ml measured with flow cytometry

Time frame: 6 months

Concentration of Extracellular Vesicles From Leukocytes

Concentration of extracellular vesicles from leukocytes/ ml measured with flow cytometry

Time frame: 6 months