Differences in Action of Atorvastatin and Ezetimibe in Lowering Low-Density Lipoprotein Cholesterol and Effect on Endothelial Function:– Randomized Controlled Trial –

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Background: The aim of this study was to compare the effect on endothelial function of increasing statin dose to add-on ezetimibe in patients with coronary artery disease (CAD) already treated with statin. Methods and Results: Two-hundred and forty-three patients with CAD and low-density lipoprotein cholesterol (LDL-C) ≥70mg/dl even after treatment with atorvastatin (10mg) were prospectively randomized to the ezetimibe addition (10mg) group (A10E10; n=117) or to the double atorvastatin dose (to 20mg; A20; n=133) group for 12 weeks. Primary endpoint was change in endothelial function measured by logarithmic-scale reactive hyperemia index (L_RHI). After treatment, high-sensitivity C-reactive protein (hs-CRP) and all lipids except triglyceride and high-density lipoprotein cholesterol were significantly reduced in both groups. The mean percent changes in LDL-C for the A10E10 and A20 groups were –25.8% and –9.1%, respectively (P<0.001). L_RHI increased from 0.47 to 0.62 in the A20 group (P<0.001), but not in the A10E10 group (from 0.45 to 0.48, P=0.399). Absolute change in L_RHI was significantly higher in the A20 than A10E10 group (0.02±0.29 vs. 0.16±0.27, P<0.001). Conclusions: Statin and ezetimibe have different effects on endothelial function independent from LDL-C-lowering effects.