A pilot study of ezetimibe vs. atorvastatin for improving peripheral microvascular endothelial function in stable patients with type 2 diabetes mellitus.

Seigo Sugiyama,Hideaki Jinnouchi,Tomio Jinnouchi,Fumio Miyamoto,Kunio Hieshima,Kunihiko Matsui,Tomoko Suzuki,Keizo Kajiwara,Noboru Kurinami

doi:10.1186/s12944-015-0028-z

Seigo Sugiyama, Hideaki Jinnouchi + Show 7 more

Open Access

https://doi.org/10.1186/s12944-015-0028-z

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Abstract

BackgroundElevated cholesterol in type 2 diabetes mellitus (DM) can cause endothelial dysfunction. An effective clinical therapy to improve endothelial dysfunction remains to be established. Different cardiovascular actions between treatments for the inhibition of cholesterol absorption and the suppression of cholesterol synthesis for achieving improvement in endothelial function are unknown in DM.MethodsStable patients with type 2 DM and mildly elevated low-density lipoprotein cholesterol were enrolled. We evaluated peripheral microvascular endothelial function using reactive hyperemia peripheral arterial tonometry (RH-PAT) examination and calculated a natural logarithmic transformed value for the RH-PAT index (LnRHI). We randomly assigned 33 patients to each monotherapy: cholesterol synthesis suppression using atorvastatin (5 mg/day, n = 16) or cholesterol absorption inhibition using ezetimibe (10 mg/day, n = 17). Patients were prospectively followed for 6 months. Serum lipids and LnRHI were repeatedly examined before and after each therapy.ResultsLDL significantly decreased in both groups, but the percent changes of LDL showed a greater decrease in the atorvastatin group compared with the ezetimibe group (−34.5 ± 7.8% vs. −21.9 ± 9.6%, p < 0.01). Serum levels of non-esterified free fatty acids (NEFA) significantly decreased in the ezetimibe group but not in the atorvastatin group (ezetimibe group: 561.1 ± 236.8 to 429.7 ± 195.9, p < 0.01; atorvastatin group: 538.8 ± 319.5 to 520.2 ± 227.3, p = 0.75). The percent decrease in NEFA was significantly greater in the ezetimibe group compared with the atorvastatin group (−19.9 ± 27.4% vs. 11.3 ± 44.1%, p < 0.05). LnRHI showed a significant increase in the ezetimibe group but not in the atorvastatin group (ezetimibe group: 0.471 ± 0.157 to 0.678 ± 0.187, p < 0.01; atorvastatin group: 0.552 ± 0.084 to 0.558 ± 0.202, p = 0.64). The percent changes in LnRHI were significantly greater in the ezetimibe group compared with the atorvastatin group (63.3 ± 89.2% vs. 7.4 ± 41.2%, p < 0.05).ConclusionsIn patients with type 2 DM, ezetimibe monotherapy significantly reduced LDL and NEFA, and improved peripheral microvascular endothelial dysfunction. Ezetimibe could potentially exhibit beneficial effects on lipid disorders and microvascular endothelial dysfunction in DM.

Highlights

Elevated cholesterol in type 2 diabetes mellitus (DM) can cause endothelial dysfunction
Patients were randomly allocated by using permuted-block randomization of six to either the ezetimibe group (10 mg/day) as the cholesterol absorption inhibition therapy or the atorvastatin group (5 mg/day) as the cholesterol synthesis suppression therapy for 6 months
There was no significant difference in peripheral microvascular endothelial function assessed by logarithmic transformed value for the Reactive hyperemia peripheral arterial tonometry (RH-PAT) index (LnRHI) values in the RH-PAT examination between groups at baseline (Table 2)

Summary

Introduction

Elevated cholesterol in type 2 diabetes mellitus (DM) can cause endothelial dysfunction. Type 2 diabetes mellitus (DM) is a high-risk clinical condition for cardiovascular disease [1]. Treatment strategies that may exhibit favorable effects on cardiovascular function are thought to have beneficial clinical value in DM. Vascular endothelial dysfunction is a significant and independent predictor of future cardiovascular events [2], and the presence of DM and elevated low-density lipoprotein cholesterol (LDL) are recognized as important pathological conditions leading to endothelial dysfunction in clinical practice [3]. We previously reported the clinical utility and significance of RH-PAT testing in terms of prognostic value [8,9], and on the interventional effects in patients with risk factors for cardiovascular disease [10,11]

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