Role of Immune Responses After Acute Myocardial Infarction

Study Overview
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Brief Summary
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The fascinating role of lymphocyte subtypes in the development of coronary artery disease may be a new strategic target for understanding and therapy of acute myocardial infarction. The determinants of cell viability are unknown, postulating that they arise from factors not only related to microcirculation or energy expenditure, but also to inflammatory and immune responses. Furthermore, the intense mobilization of progenitor cells secondary to myocardial infarction triggers large lymphocyte proliferation that colonizes plaques in development, contributing to recurrent ischemic outcomes. This project aims to evaluate the immune and metabolic mechanisms involved in the recovery of the ischemic myocardium and coronary disease progression.

Detailed Description
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Specifically, the investigators will study the innate and adaptive immunity, with emphasis on lymphocytes subtypes involved in the early and late surrogate outcomes of patients with acute myocardial infarction, their characterization (B1, B2 and T lymphocytes) in cell culture and by flow-cytometry, and immune responses (IgM and IgG for oxLDL and specific epitopes of apoB). In addition, the project will evaluate new biomarkers identified by studies of metabolomics, as well as the corresponding signaling pathways. Therapeutic pharmacological strategies and changes on intestinal microbiota will be evaluated since the acute phase of myocardial infarction up to 6 months. In the study, the investigators will compared four arms of combined therapy: clopidogrel with rosuvastatin; or clopidogrel with simvastatin; or ticagrelor with rosuvastatin; or ticagrelor with simvastatin. The investigator's hypothesis is that the improvement of microcirculation with rosuvastatin and ticagrelor (synergic pleiotropic effects) may decrease the infarcted mass area, resulting in better left ventricular ejection fraction when compared to the other combined therapies. The monitoring and genotype of microbiota will be examined together the metabolomics and cardiac MRIs obtained at the acute phase of MI and after 1-mo and 6-mo FU.

Official Title
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Role of Innate and Adaptive Immunity After Acute Myocardial Infarction BATTLE-AMI Study (B And T Types of Lymphocytes Evaluation in Acute Myocardial Infarction)

Conditions
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Myocardial Fibrosis

Intervention / Treatment
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* Drug: Rosuvastatin plus clopidogrel
* Drug: Rosuvastatin plus ticagrelor
* Drug: Simvastatin plus clopidogrel
* Drug: Simvastatin plus ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Stable patients with ST elevation myocardial infarction (STEMI) treated with thrombolytics in the first 6h or the initial of symptoms of MI. Exclusion Criteria: Contraindication or known intolerance to the study drug protocol Those with comorbidities such as neoplasm, renal insufficiency (stage 4 or higher) Patients should be randomized in the first 24 hours of AMI and treated by one of the four combined therapies at least 2h prior to coronary angiogram followed by percutaneous intervention when necessary.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rosuvastatin plus clopidogrel<br>rosuvastatin 40 mg and clopidogrel 75 mg | Drug: Rosuvastatin plus ticagrelor<br>* Crestor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo<br>* Other names: Crestor & Brilinta;Drug: Simvastatin plus clopidogrel<br>* Zocor 40 mg plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo<br>* Other names: Zocor plus Plavix;Drug: Simvastatin plus ticagrelor<br>* Zocor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo<br>* Other names: Zocor & Brilinta;|
| Active Comparator: Rosuvastatin plus ticagrelor<br>Rosuvastatin 40 mg plus ticagrelor 90 mg bid | Drug: Rosuvastatin plus clopidogrel<br>* Crestor 40 mg daily plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo<br>* Other names: Crestor & Plavix;Drug: Simvastatin plus clopidogrel<br>* Zocor 40 mg plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo<br>* Other names: Zocor plus Plavix;Drug: Simvastatin plus ticagrelor<br>* Zocor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo<br>* Other names: Zocor & Brilinta;|
| Active Comparator: simvastatin plus clopidogrel<br>Simvastatin 40 mg plus clopidogrel 75 mg | Drug: Rosuvastatin plus clopidogrel<br>* Crestor 40 mg daily plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo<br>* Other names: Crestor & Plavix;Drug: Rosuvastatin plus ticagrelor<br>* Crestor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo<br>* Other names: Crestor & Brilinta;Drug: Simvastatin plus ticagrelor<br>* Zocor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo<br>* Other names: Zocor & Brilinta;|
| Active Comparator: Simvastatin plus ticagrelor<br>Simvastatin 40 mg plus ticagrelor 90 mg bid | Drug: Rosuvastatin plus clopidogrel<br>* Crestor 40 mg daily plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo<br>* Other names: Crestor & Plavix;Drug: Rosuvastatin plus ticagrelor<br>* Crestor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo<br>* Other names: Crestor & Brilinta;Drug: Simvastatin plus clopidogrel<br>* Zocor 40 mg plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo<br>* Other names: Zocor plus Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the left ventricular function (MRI) between the four combined treatments, after STEMI | The effects of treatments on the left ventricular function will be measured by MRI | 1-mo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the effects of the four combined therapies on the left ventricular function after STEMI | Variables will be examined by MRI | 3-d | 
| To compare the effects of the four combined therapies on the left ventricular function after STEMI | Variables will be examined by MRI | 6-mo | 
| To compare the effects of the four combined therapies on the infarcted mass area after STEMI | Variables will be examined by MRI | 1-mo | 
| To compare the effects of the four combined therapies on the infarcted mass area after STEMI | Variables will be examined by MRI | 6-mo | 
| To compare the effects of the four combined therapies on the percentage of subjects with left ventricular ejection fraction < 40% after STEMI | Variables will be examined by MRI | 1-mo | 
| To compare the effects of the four combined therapies on the percentage of subjects with left ventricular ejection fraction < 40% after STEMI | Variables will be examined by MRI | 6-mo | 
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction after STEMI | Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI | 1-d | 
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction after STEMI | Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI | 1-mo | 
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction after STEMI | Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI | 6-mo | 
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with infarcted mass area after STEMI | Lymphocyte subtypes quantified by flow-cytometry and infarcted mass area by MRI | 1-d | 
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with infarcted mass area after STEMI | Lymphocyte subtypes quantified by flow-cytometry and infarcted mass area by MRI | 1-mo | 
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with infarcted mass area after STEMI | Lymphocyte subtypes quantified by flow-cytometry and infarcted mass area by MRI | 6-mo | 
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction <40% after STEMI | Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI | 1-d | 
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction <40% after STEMI | Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI | 1-mo | 
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction <40% after STEMI | Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI | 6-mo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Ventricular function, left