Abstract
Low-dose statin therapy in combination with ezetimibe, an inhibitor of intestinal cholesterol absorption, lowers plasma LDL-cholesterol levels to a similar degree as high-dose statin monotherapy. This study assessed whether similar LDL-cholesterol lowering with simvastatin/ezetimibe combination therapy improves fasting and postprandial arterial endothelial function compared to high-dose statin therapy alone. Multicenter, double-blind, crossover trial in 100 abdominally obese patients with the metabolic syndrome, randomized to 6 weeks' treatment with simvastatin 80mg or simvastatin/ezetimibe 10/10mg. Flow mediated dilatation (FMD) and peripheral arterial tonometry (EndoPAT) as well as plasma lipids were measured in the fasting state and after an oral lipid load at baseline and after both treatments. Fasting LDL-cholesterol levels (3.57mmol/L at baseline) were reduced to 1.79mmol/L following treatment with simvastatin 80mg and 1.81mmol/L with simvastatin/ezetimibe 10/10mg, respectively. Plasma lipids were similar at 4h after an oral lipid load following both treatments for 6 weeks. Fasting endothelial function was also similar with both treatments when assessed by FMD (adjusted mean±SE: 4.35±0.19 vs. 4.43±0.18; P=0.777) and EndoPAT (2.12±0.05 vs 2.20±0.05; P=0.304). After an oral fat load, changes in endothelial function were also comparable for both treatments as assessed by FMD (-0.34±0.21 vs.-0.43±0.20; P=0.766) and EndoPAT (0.00±0.07 vs.-0.04±0.08; P=0.712). Treatment with simvastatin/ezetimibe 10/10mg induced no difference in endothelial function in the fasting and postprandial state compared to simvastatin 80mg while attaining similar LDL-c levels in obese patients with metabolic syndrome.
Published Version
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