Simvastatin Effect on Inflammation and Endothelial Function After Myocardial Infarction

Study Overview
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Brief Summary
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During myocardial infarction, inflammatory response may negatively influence ventricle wall remodeling as well as endothelium-dependent vasomotor function in the coronary and systemic arterial systems. Statins have been consistently proved to attenuate inflammation and improve endothelial function. In this study, we tested the effect of different doses of statin on inflammatory response and endothelium-dependent vasodilation.

Detailed Description
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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. The intensity of this inflammatory upregulation is strongly related to the incidence of recurrent coronary events. High dose potent statins can rapidly reduce plasma levels of cholesterol-rich lipoproteins and inflammatory activity in subjects during ACS. By inference, it is plausible to hypothesize that these effects during the acute phase of myocardial infarction may influence the post-discharge endothelial dysfunction. So far, data is unavailable to verify this assumption or to define the potency required for such statin anti-inflammatory effect in myocardial infarction patients. The present study aim to investigate the role of statin dose 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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Phase 4 Study of the Effect of Simvastatin Treatment on Inflammatory Response and Endothelial Function After Myocardial Infarction

Conditions
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Myocardial Infarction, Inflammation, Endothelial Dysfunction

Intervention / Treatment
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* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Less than 24 hours after the onset of MI 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 at least 6 months prior the myocardial infarction

Ages Eligible for Study
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Minimum Age: 45 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: No lipid-lowering<br>No lipid-lowering treatment during the first 7 days and then simvastatin 20 mg/day for three additional weeks, till the endothelial function assessment | Drug: Simvastatin<br>* Simvastatin<br>|
| Experimental: Simvastatin 20 mg<br>Simvastatin 20 mg/day for 30 days, till the endothelial function assessment | Drug: Simvastatin<br>* Simvastatin<br>|
| Experimental: Simvastatin 40 mg<br>Simvastatin 40 mg/day for 7 days and then switched to simvastatin 20mg/day for additional 3 weeks, till the endothelial function assessment | Drug: Simvastatin<br>* Simvastatin<br>|
| Experimental: Simvastatin 80 mg<br>Simvastatin 80 mg/day for 7 days and then switched to simvastatin 20 mg/day for additional 3 weeks, till the endothelial function assessment | Drug: Simvastatin<br>* Simvastatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elevation of plasma C reactive protein | Changes in CRP levels between the first and fifth day after myocardial infarction | Five days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial Artery Endothelial function |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myocardial infarction, inflammation, endothelial dysfunction