Additive Effect of Ezetimibe Upon Simvastatin During Myocardial Infarction

Study Overview
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Brief Summary
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During acute coronary syndromes (ACS), the generation of inflammatory mediators negatively influences arterial wall remodeling and the endothelium-dependent vasomotor function in the coronary and systemic arterial systems. In fact, the intensity of the inflammatory upregulation is strongly related to the incidence of recurrent coronary events. The investigators previously demonstrated that high dose potent statins can rapidly reduce plasma levels of cholesterol-rich lipoproteins and inflammatory activity in subjects during ACS. In addition, such statin treatment attenuates the post-discharge endothelial dysfunction of these patients. By inference, it is plausible to hypothesize that these beneficial effects during ACS may be intensified by an additive lowering of plasma cholesterol through the treatment with ezetimibe. So far, data is unavailable to verify this assumption. In parallel, data from animal models have suggested that both statins and ezetimibe may reduce insulin sensitivity by their effect on cholesterol content and, by this way, on insulin signaling in liver cells. In this context, the present study aims to investigate the role of the addition of ezetimibe upon statin treatment on stress-induced insulin resistance and on the time-course of the inflammatory response during the acute phase of myocardial infarction and its late effect on endothelium-dependent arterial dilation.

Official Title
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Additive Effect of Ezetimibe Upon Simvastatin Treatment on Systemic Inflammatory Activity and Endothelial Function During Myocardial Infarction

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Ezetimibe-Simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: less than 24 hours after the onset of myocardial infarction symptoms ST-segment elevation of a least 1 mm (frontal plane) or 2 mm (horizontal plane) in two contiguous leads myocardial necrosis, as evidenced by increased CK-MB and troponin levels Exclusion Criteria: use of statins for the last 6 months before myocardial infarction

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ezetimibe-Simvastatin 10/40 mg<br> | Drug: Ezetimibe-Simvastatin<br>* Ezetimibe-Simvastatin 10-40 mg/day during the first 7 days and then 20 mg/day for 3 more weeks until the evaluation of flow-mediated brachial artery dilation<br>* Other names: Vytorin;|
| Active Comparator: Simvastatin 40 mg<br> | Drug: Simvastatin<br>* Simvastatin 40 mg/day during the first 7 days and then 20 mg/day for 3 more weeks until the evaluation of flow-mediated brachial artery dilation<br>* Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C- reactive Protein (CRP) elevation during the first 7 days after myocardial infarction |  | 5th day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial function 30 days after myocardial infarction |  | 30th day | 
| Stress Insulin Resistance | Evaluation of the change in plasma glucose, insulin and C-peptide from admission to the fifth day after myocardial infarction | 5th day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myocardial infarction, systemic inflammatory activity, endothelial function