THE EFFECT OF SIMVASTATIN VERSUS COMBINED SIMVASTATIN/EZETIMIBE TREATMENT ON THE CONCENTRATION OF SMALL DENSE LOW-DENSITY LIPOPROTEIN PARTICLES IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA

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 ones[4, 5] and thus associated with increased risk for coronary artery disease[6] 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 ezetimibe/simvastatin combination was more effective than ezetimibe and simvastatin monotherapy in reducing atherogenic lipoprotein subfractions in patients with primary hypercholesterolemia.[11] However, in this study ezetimibe/simvastatin 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.

Both simvastatin 40 mg and simvastatin/ezetimibe 10/10 mg result in LDL-C reductions of approximately the same magnitude.[13,14] However, the differential effects of these two treatment options on sdLDL-C concentration have not been assessed.

Study design Randomized, open label study.

Aim of the study The aim of the present study is to compare the effects of simvastatin 40 mg versus simvastatin/ezetimibe 10/10 mg on sdLDL-C concentration.

Materials and Methods Study population Consecutive patients with primary hypercholesterolemia (n=100) attending the Outpatient Lipid and Obesity Clinic of the University Hospital of Ioannina, Ioannina, Greece will participate in the present study.