Simvastatin Effect on Inflammation and Endothelial Function After Myocardial Infarction - Full Text View

Purpose

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.

Condition	Intervention	Phase
Myocardial Infarction Inflammation Endothelial Dysfunction	Drug: Simvastatin	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Phase 4 Study of the Effect of Simvastatin Treatment on Inflammatory Response and Endothelial Function After Myocardial Infarction

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack Statins

Drug Information available for: Simvastatin

U.S. FDA Resources

Further study details as provided by Brasilia Heart Study Group:

Primary Outcome Measures:

Elevation of plasma C reactive protein [ Time Frame: Five days ] [ Designated as safety issue: No ]
Changes in CRP levels between the first and fifth day after myocardial infarction

Secondary Outcome Measures:

Brachial Artery Endothelial function [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Enrollment:	58
Study Start Date:	November 2008
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	45 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00906451

Locations

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

Sponsors and Collaborators

Brasilia Heart Study Group

Investigators

Study Chair:

Andrei C Sposito, MD, PhD

University of Brasilia Medical School

More Information

Publications:

Sposito AC, Santos SN, de Faria EC, Abdalla DS, da Silva LP, Soares AA, Japiassú 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. Epub 2011 Mar 3.

Responsible Party:	Andrei C. Sposito, University of Brasilia Medical School
ClinicalTrials.gov Identifier:	NCT00906451 History of Changes
Other Study ID Numbers:	Simvastatin Post-MI
Study First Received:	May 19, 2009
Last Updated:	June 21, 2011
Health Authority:	Brazil: National Committee of Ethics in Research

Keywords provided by Brasilia Heart Study Group:

myocardial infarction
inflammation
endothelial dysfunction

Additional relevant MeSH terms:

Infarction
Inflammation
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

Simvastatin
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013