Effect of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients With Acute Myocardial Infarction

Study Overview
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Brief Summary
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Of the patients diagnosed with ST-segment elevation myocardial infarction (STEMI) who underwent reperfusion therapy and have thrombolysis in myocardial infarction (TIMI) 3 flow, about 40% have flow alterations in the coronary microcirculation, which leads to worse remodeling of the left ventricle with a consequent increase in the mortality of this population. Clopidogrel is the only known antiplatelet medication that brings benefits to the coronary microcirculation. Ticagrelor is significantly superior to clopidogrel in terms of decreasing mortality. The main objective of this study is to compare the effect of ticagrelor versus clopidogrel on the coronary microcirculation by the Myocardial Perfusion Score Index (MPSI) obtained using Microbubble Contrasted Echocardiography (MCE) in patients who have STEMI and treated with thrombolysis.

Detailed Description
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The present project should prospectively include patients participating in the TREAT study, who are including individuals with Acute Myocardial Infarction (AMI) treated with fibrinolytic and openly randomized to ticagrelor or clopidogrel within 24 hours of the onset of symptoms. Patients will be submitted to coronary angiography within 4 (± 2) days of the onset of symptoms, and those who, at the end of coronary angiography, present residual obstruction in the culprit vessel of less than 50% and have TIMI 3 flow, regardless of have undergone percutaneous coronary intervention will be included. Following, on day 2 (± 1) days after coronary angiography (therefore 6 ± 3 days from the onset of symptoms), they will be submitted to microcirculation perfusion evaluation by means of MPSI (myocardial perfusion score index) obtained by MCE (Microbubble contrasted echocardiography) - blood collection for evaluation of Platelet aggregability will be performed immediately prior to the start of MCE. Finally, in order to evaluate left ventricular remodeling, patients will undergo a new Echocardiography within 90 (± 10) days after discharge.

Official Title
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Effect of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients With Acute Myocardial Infarction

Conditions
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Coronary Microvascular Disease, Ticagrelor, Thrombolysis, Microbubble Contrasted Echocardiography

Intervention / Treatment
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* Diagnostic Test: Microbubble Contrasted Echocardiography
* Diagnostic Test: Platelet Aggregability
* Diagnostic Test: Laboratory


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age from 18 years old to 75 years old. Patients with a ST-segment elevation AMI with up to 24 hours duration, documented by ischemic symptoms due to atherosclerosis> 10 minutes at rest, treated with pharmacological thrombolysis, acetylsalicylic acid (ASA) and Clopidogrel or Ticagrelor. Cardiac catheterization performed within 4 (± 2) days of the onset of symptoms, which at the end of coronary angiography showed residual obstruction in the culprit artery <50% with TIMI 3 flow regardless of whether or not the percutaneous coronary intervention was performed. Exclusion Criteria: Previous infarction known from the same wall as the current one Any contraindication to the use of Clopidogrel or Ticagrelor Need for oral anticoagulation therapy or aspirin doses greater than 100mg per day. Concomitant oral or intravenous therapy with strong inhibitors of Cytochrome P450, family 3, subfamily A (CYP3A), Substrates of CYP3A with narrow therapeutic indices or strong inducers of CYP3A High risk of bradyarrhythmias Dialysis therapy Clinically important thrombocytopenia known Clinically Significant Anemia Pregnancy or lactation Contraindications to fibrinolytic therapy

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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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ticagrelor<br>Patients will be randomized to have Ticagrelor 90mg BID | Diagnostic Test: Microbubble Contrasted Echocardiography<br>* Myocardial Perfusion Score Index (MPSI) obtained using Microbubble Contrasted Echocardiography<br>Diagnostic Test: Platelet Aggregability<br>* Obtained using Multiplate Analyzer<br>Diagnostic Test: Laboratory<br>* it will be collected at patients arrival, Reative C-Protein, BNP, CK-mass, Troponine, interleukine-6, Creatinine.<br>|
| Other: Clopidogrel<br>Patientes will be randomized to have Clopidogrel 75mg once a day | Diagnostic Test: Microbubble Contrasted Echocardiography<br>* Myocardial Perfusion Score Index (MPSI) obtained using Microbubble Contrasted Echocardiography<br>Diagnostic Test: Platelet Aggregability<br>* Obtained using Multiplate Analyzer<br>Diagnostic Test: Laboratory<br>* it will be collected at patients arrival, Reative C-Protein, BNP, CK-mass, Troponine, interleukine-6, Creatinine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Perfusion Score Index (MPSI) | Obtained using Microbubble Contrasted Echocardiography | 4 (±3) days after Cardiac catheterization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular remodeling 90 days after de AMI, using Echocargiography parameters (End diastolic volume, end systolic volume and ejection Fraction) | To compare the parameters of left ventricular remodeling (End diastolic volume, End Systolic Volume, Ejection Fraction) at after 90 days after discharge from the ticagrelor and clopidogrel groups | after 90 days after discharge | 
| number of myocardial segments with perfusion deficit in coronary microcirculation | To evaluate the number of myocardial segments with perfusion deficit in coronary microcirculation in the ticagrelor and clopidogrel groups | 4 (±3) days after Cardiac catheterization | 
| MPSI in patients submitted to angioplasty | To evaluate MPSI in the subgroups of patients submitted to angioplasty and not submitted to angioplasty | 4 (±3) days after Cardiac catheterization | 
| Patients who used clopidogrel prior to randomization and were randomized to ticagrelor | To evaluate MPSI in subgroups of patients who used clopidogrel prior to randomization and were randomized to ticagrelor | 4 (±3) days after Cardiac catheterization | 
| Elective versus Urgent Percutaneous Coronary Intervention (PCI) | To compare the ticagrelor and clopidogrel groups in patients who had elective or urgent PCI | 4 (±3) days after Cardiac catheterization | 
| Platelet aggregability | To evaluate the platelet aggregability in the ticagrelor and clopidogrel groups obtained immediately before Myocardial Contrasted Echocardiography (MCE) by Multiplate | 4 (±3) days after Cardiac catheterization | 
| Time Ticagrelor or Clopidogrel is administered | Evaluate the main objective of the study in two subgroups: 1) Ticagrelor or Clopidogrel administered less than 12 hours from the symptoms onset. 2) greater than or equal to 12 hours from the symptoms onset | 4 (±3) days after Cardiac catheterization |