 Hypercholesterolemia is a major risk factor for atherosclerosis and coronary heart disease CHD.1 Epidemiological and clinical studies have demonstrated that aggressive lowering of low-density lipoprotein cholesterol LDL-C reduces morbidity and mortality in patients with or without CHD.1-3 LDL consists of an heterogeneous population of particles with respect to size, density and chemical composition. Several studies have shown that small, dense LDL sdLDL particles are more atherogenic than large, buoyant ones4, 5 and thus associated with increased risk for coronary artery disease6 or stroke.7 Statins, the mainstay of lipid lowering therapy, achieve significant reductions in LDL-C levels and are suggested to lower all LDL subfractions, possibly as a result of the statin-induced stimulation of LDL-receptor-mediated catabolism.8 Moreover, several studies have shown that abnormalities in LDL subfraction profile are amenable to correction with statins.9 Ezetimibe monotherapy has also been found to significantly reduce concentrations of all LDL subfractions.10 The combination of ezetimibe with low dose of a statin results in similar LDL-C lowering compared with high dose of the same statin. A recent study demonstrated that ezetimibesimvastatin combination was more effective than ezetimibe and simvastatin monotherapy in reducing atherogenic lipoprotein subfractions in patients with primary hypercholesterolemia.11 However, in this study ezetimibesimvastatin combination was more potent in reducing LDL-C levels compared with either monotherapy.11 In another study, the addition of ezetimibe in patients already receiving atorvastatin decreased LDL-C values exclusively by reducing the concentrations of large, buoyant LDL subfractions.12 It is so far unknown whether high-dose of a statin would reduce sdLDL-C level more than low-dose statin plus ezetimibe therapy for the same degree of LDL-C lowering. 