Simvastatin Effect on Inflammation and Endothelial Function After Myocardial Infarction

Phase 4 Study of the Effect of Simvastatin Treatment on Inflammatory Response and Endothelial Function After Myocardial Infarction

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Inflammation; Endothelial Dysfunction
• Intervention / Treatment: Drug: Simvastatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • DF
    • Brasilia, DF, Brazil, 70000000
      • Hospital de Base do Distrito Federal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No lipid-lowering; 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; Simvastatin
Experimental: Simvastatin 20 mg; Simvastatin 20 mg/day for 30 days, till the endothelial function assessment	Drug: Simvastatin; Simvastatin
Experimental: Simvastatin 40 mg; 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; Simvastatin
Experimental: Simvastatin 80 mg; 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; Simvastatin

What is the study measuring?

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	Time Frame
Brachial Artery Endothelial function	30 days

Collaborators and Investigators

• Sponsor: Brasilia Heart Study Group
• Investigators: Study Chair: Andrei C Sposito, MD, PhD, University of Brasilia Medical School

Publications and helpful links

General Publications

• Sposito AC, Santos SN, de Faria EC, Abdalla DS, da Silva LP, Soares AA, Japiassu AV, Quinaglia e Silva JC, Ramires JA, Coelho OR. Timing and dose of statin therapy define its impact on inflammatory and endothelial responses during myocardial infarction. Arterioscler Thromb Vasc Biol. 2011 May;31(5):1240-6. doi: 10.1161/ATVBAHA.110.218685. Epub 2011 Mar 3.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: May 19, 2009
• First Submitted That Met QC Criteria: May 20, 2009
• First Posted (Estimate): May 21, 2009

Study Record Updates

• Last Update Posted (Estimate): June 23, 2011
• Last Update Submitted That Met QC Criteria: June 21, 2011
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: endothelial dysfunction; myocardial infarction; inflammation
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Inflammation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: Simvastatin Post-MI