Additive Effect of Ezetimibe Upon Simvastatin During Myocardial Infarction

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

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.

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

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

Evaluation of the change in plasma glucose, insulin and C-peptide from admission to the fifth day after myocardial infarction

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