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.

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.

No lipid-lowering treatment during the first 7 days and then simvastatin 20 mg/day for three additional weeks, till the endothelial function assessment

Simvastatin 40 mg/day for 7 days and then switched to simvastatin 20mg/day for additional 3 weeks, till the endothelial function assessment

Simvastatin 80 mg/day for 7 days and then switched to simvastatin 20 mg/day for additional 3 weeks, till the endothelial function assessment

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

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.