Vascular and metabolic effects of ezetimibe combined with simvastatin in patients with hypercholesterolemia

•Vyto10, Vyto20, and Simva20 improved flow-mediated dilation.•Ezetimbe/simvastatin reduced blood pressure and visceral obesity.•Ezetimbe/simvastatin improved insulin sensitivity, compared with simvastatin alone.•However, these effects depend on dosages of simvastatin.•These findings may explain the results of a recent IMPROVE-IT study.

BackgroundEzetimibe demonstrates decreasing visceral fat and improving insulin sensitivity (IS) in animals and humans. We first reported that simvastatin dose-dependently worsens insulin sensitivity. Whether ezetimibe may compensate untoward effects of simvastatin, depending on dosages of simvastatin has not been investigated in patients with hypercholesterolemia, compared with simvastatin alone.MethodsThis was a randomized, single-blind, placebo-controlled, parallel study. Fifty-one in each group were given placebo, ezetimibe 10 mg combined with simvastatin 10 mg (Vyto10), ezetimibe 10 mg combined with simvastatin 20 mg (Vyto20), or simvastatin 20 mg alone (Simva20) daily for 2 months.ResultsPlacebo, Vyto10, Vyto20, and Simva20 improved flow-mediated dilation relative to baseline measurements. Placebo therapy did not significantly change insulin and IS and adiponectin levels and visceral fat area (VFA) and VFA/subcutaneous fat area (SFA) relative to baseline measurements. Vyto10 therapy significantly decreased CRP and insulin levels and increased adiponectin levels and IS, and reduced VFA, VFA/SFA, and blood pressure. Vyto20 therapy did not significantly change insulin levels and IS and adiponectin levels but significantly reduced CRP levels and VFA, VFA/SFA, and blood pressure. Simva20 therapy significantly decreased adiponectin levels and IS but did not significantly change VFA, VFA/SFA, and blood pressure. Of note, these different effects of each therapy were significant by ANOVA.ConclusionsVyto10, Vyto20, and Simva20 showed significant reduction of LDL cholesterol levels and improvement of flow-mediated dilation in patients with hypercholesterolemia. However, Vyto10, Vyto20, and Simva20 showed significantly differential metabolic effects, depending on dosages of simvastatin.