Kwang Kon Koh1, Pyung Chun Oh2, Ichiro Sakuma3, Eun Young Kim4, Yonghee Lee5, Toshio Hayashi6, Seung Hwan Han2, Yae Min Park2, Eak Kyun Shin2. 1. Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea. Electronic address: kwangk@gilhospital.com. 2. Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea. 3. Cardiovascular Medicine, Hokko Memorial Clinic, Sapporo, Japan. 4. Radiology, Gachon University Gil Medical Center, Incheon, Republic of Korea. 5. Department of Statistics, University of Seoul, Seoul, Republic of Korea. 6. Geriatric Department, Nagoya University, Nagoya, Japan.
Abstract
BACKGROUND:Ezetimibe 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. METHODS: This was a randomized, single-blind, placebo-controlled, parallel study. Fifty-one in each group were given placebo, ezetimibe 10mg combined with simvastatin 10mg (Vyto10), ezetimibe 10mg combined with simvastatin 20mg (Vyto20), or simvastatin 20mg alone (Simva20) daily for 2months. RESULTS:Placebo, 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. CONCLUSIONS: Vyto10, 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.
RCT Entities:
BACKGROUND:Ezetimibe 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. METHODS: This was a randomized, single-blind, placebo-controlled, parallel study. Fifty-one in each group were given placebo, ezetimibe 10mg combined with simvastatin 10mg (Vyto10), ezetimibe 10mg combined with simvastatin 20mg (Vyto20), or simvastatin 20mg alone (Simva20) daily for 2months. RESULTS: Placebo, 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. CONCLUSIONS: Vyto10, 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.
Authors: Namki Hong; Yong Ho Lee; Kenichi Tsujita; Jorge A Gonzalez; Christopher M Kramer; Tomas Kovarnik; George N Kouvelos; Hiromichi Suzuki; Kyungdo Han; Chan Joo Lee; Sung Ha Park; Byung Wan Lee; Bong Soo Cha; Eun Seok Kang Journal: Endocrinol Metab (Seoul) Date: 2018-05-04