Abstract 4081: The Effects of Low-Dose Simvastatin and Ezetimibe Compared to High-Dose Simvastatin on Postprandial Lipids and Endothelial Function in Patients with the Metabolic Syndrome
Background and Aims Insulin resistance is associated with postprandial hyperlipidemia and endothelial dysfunction. Inhibiting cholesterol absorption may influence postprandial lipid metabolism and may therefore have effects on postprandial endothelial function. Aim of the present study is to compare the effects of combination therapy of low-dose simvastatin and ezetimibe with high-dose simvastatin monotherapy on (postprandial) lipid profiles and endothelial function in patients with the metabolic syndrome.
Methods Prospective, randomized, crossover, double blind trial in 19 male patients with the metabolic syndrome with high-dose simvastatin 80 mg (SIM80) versus combination therapy of low-dose simvastatin 10 mg with ezetimibe 10 mg (SIM/EZE10/10). Endothelial function was ultrasonographically determined with flow-mediated dilation measurements.
Results: Mean age was 54 ± 7 years. Weight, waist circumference and body fat remained stable during the study. Plasma LDL-cholesterol concentration was similarly reduced by both treatment regimes (from 3.7 ± 0.7 mmol/l to 2.1 ± 0.5 mmol/l). With SIM80 postprandial endothelial function was significantly decreased (6.9% versus 4.3%), contrary to SIM/EZE10/10 (7.6% versus 7.7%). No differences were observed in fasting and postprandial lipid profiles between either treatment regimes. Before as well as 3, 4 and 8 hours after an oral fat load plasma concentrations of IL-6 were slightly higher during treatment with SIM80 compared to SIM/EZE10/10.
Conclusion Combination therapy with low-dose simvastatin and ezetimibe preserved postprandial endothelial function, contrary to treatment with high-dose simvastatin monotherapy in metabolic syndrome patients, whereas no differences were observed in postprandial lipid profiles between either treatment regimes. By preserving postprandial endothelial function in the present study, combination therapy of ezetimibe with statins may additionally reduce the cardiovascular risk of the metabolic syndrome beyond LDL-cholesterol lowering.