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

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.

• Authors: Kwang Kon Koh, Pyung Chun Oh, Ichiro Sakuma, Eun Young Kim, Yonghee Lee, Toshio Hayashi, Seung Hwan Han, Yae Min Park, Eak Kyun Shin
• Journal: International journal of cardiology (Int J Cardiol) Vol. 199 Pg. 126-31 (Nov 15 2015) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 26188833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• ADIPOQ protein, human
• Adiponectin
• Anticholesteremic Agents
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypolipidemic Agents
• Insulin
• C-Reactive Protein
• Simvastatin
• Ezetimibe

Topics

• Adiponectin (metabolism)
• Aged
• Animals
• Anticholesteremic Agents (administration & dosage, pharmacology)
• Blood Pressure (drug effects)
• C-Reactive Protein (drug effects)
• Drug Therapy, Combination
• Ezetimibe (administration & dosage, pharmacology)
• Fat Body (drug effects)
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, pharmacology)
• Hypercholesterolemia (blood, drug therapy)
• Hypertension (drug therapy)
• Hypolipidemic Agents (administration & dosage, pharmacology)
• Insulin (pharmacology)
• Insulin Resistance (physiology)
• Male
• Middle Aged
• Randomized Controlled Trials as Topic
• Rats
• Simvastatin (administration & dosage, pharmacology)
• Single-Blind Method