BACKGROUND: 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). OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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).