ezetimibe--simvastatin-drug-combination and Coronary-Artery-Disease

The effects of short-term intensive lipid-lowering treatment on coronary plaque composition have not yet been sufficiently evaluated. We investigated the influence of short-term intensive lipid-lowering treatment on quantitative and qualitative changes in plaque components of non-culprit lesions in patients with acute coronary syndrome.. This was a prospective, randomized, open-label, single-center trial. Seventy patients who underwent both baseline and three-month follow-up virtual histology intravascular ultrasound were randomly assigned to either an intensive lipid-lowering treatment group (ezetimibe/simvastatin 10/40 mg, n=34) or a control statin treatment group (pravastatin 20 mg, n=36). Using virtual histology intravascular ultrasound, plaque was characterized as fibrous, fibro-fatty, dense calcium, or necrotic core. Changes in plaque components during the three-month lipid-lowering treatment were compared between the two groups.. Compared with the control statin treatment group, there was a significant reduction in low-density lipoprotein cholesterol in the intensive lipid-lowering treatment group (-20.4±17.1 mg/dL vs. -36.8±17.4 mg/dL, respectively; p<0.001). There were no statistically significant differences in baseline, three-month follow-up, or serial changes of gray-scale intravascular ultrasound parameters between the two groups. The absolute volume of fibro-fatty plaque was significantly reduced in the intensive lipid-lowering treatment group compared with the control group (-1.5±3.4 mm³ vs. 0.8±4.7 mm³, respectively; p=0.024). A linear correlation was found between changes in low-density lipoprotein cholesterol levels and changes in the absolute volumes of fibro-fatty plaque (p<0.001, R²=0.209).. Modification of coronary plaque may be attainable after only three months of intensive lipid-lowering treatment.

Topics: Aged; Cholesterol, LDL; Coronary Artery Disease; Drug Administration Schedule; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Plaque, Atherosclerotic; Pravastatin; Prospective Studies; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Patients with coronary artery disease (CAD) should be treated with statins to attain very low cholesterol levels, in order to reduce cardiovascular adverse events. More than 70% of these patients do not reach the appropriate cholesterol goal despite moderate statin doses. However, it is not known whether therapeutic uptitration with different lipid-lowering strategies has a similar "pleiotropic" effect on atherosclerotic endothelial dysfunction evaluated by measurement of endothelial progenitor cells (EPCs).. We sought to compare, in patients with stable CAD and with a low-density lipoprotein cholesterol (LDL-C) >70 mg/dL on treatment with simvastatin 20 mg, the effects on EPCs by increasing simvastatin to 80 mg versus adding ezetimibe 10 mg.. Patients (n = 68, 63 ± 9 years, 39% men) were randomly allocated to receive ezetimibe 10/simvastatin 20 mg or simvastatin 80 mg for 6 weeks. Circulating EPCs were measured by flow cytometry before and after the treatment.. Both strategies presented similar effects on metabolic parameters. The LDLs were equally reduced by ezetimibe 10/simvastatin 20 mg and simvastatin 80 mg (28.9% ± 13% vs 21.1% ± 33%; P = .46, respectively). The levels of EPCs were unaffected by ezetimibe 10/simvastatin 20 mg (median [25th, 75th]: pre- vs posttreatment, 7.0 [2.3; 13.3] vs 3.1 [0.1; 13.2] EPCs/10(4) mononuclear cells; P = .43) or simvastatin 80 mg (pre- vs posttreatment, 6.1 [2.9; 15.2] vs 4.0 [1.4; 10.7] EPCs/10(4) mononuclear cells; P = .5), and there were no differences between the groups on treatment effects (P = .9).. Among stable patients with CAD and with an LDL-C >70 mg/dL on simvastatin 20 mg, increasing simvastatin dose to 80 mg or adding ezetimibe 10 mg promoted similar further cholesterol reduction but did not have incremental effects on circulating EPCs. These data suggest that the effects of simvastatin moderate doses on EPCs are not increased by intensive lipid-lowering strategies (clinicaltrials.gov: NCT00474123).

Topics: Aged; Anticholesteremic Agents; Azetidines; Cholesterol, LDL; Coronary Artery Disease; Dose-Response Relationship, Drug; Drug Combinations; Endothelial Cells; Ezetimibe, Simvastatin Drug Combination; Female; Flow Cytometry; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Simvastatin; Stem Cells

Topics: Anticholesteremic Agents; Azetidines; Coronary Artery Disease; Drug Combinations; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Simvastatin; Uncertainty