Effect of Ezetimibe on LDL-C Lowering and Atherogenic Lipoprotein Profiles in Type 2 Diabetic Patients Poorly Controlled by Statins.

Kei Sakamoto ,Tsutomu Hirano,Motoyoshi Tsujino,Takayuki Watanabe,Mitsunobu Kawamura,Takeshi Inazawa,Akira Tanaka,Nobuo Sekine,Toru Hiyoshi,Masao Omura,Toshiyuki Horiuchi,Motoki Tagami,Tsutomu Yamazaki,Takahide Kohro,Teruo Shiba,Rina Chin,Hidehiko Hara,Keiko Ashidate,Yusaku Mori

doi:10.1371/journal.pone.0138332

Abstract

BackgroundThere exists a subpopulation of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C, representing a major risk of CVD. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks.MethodsLipid changes were assessed in a randomized, multicenter, 12-week, open-label study comparing a high-potency statin (10mg of atorvastatin or 1mg of pitavastatin) plus ezetimibe (EAT: n = 53) with a double dose of statin (20mg of atorvastatin or 2mg of pitavastatin) (DST: n = 56) in DM subjects who had failed to achieve the optimal LDL-C targets. Lipid variables were compared with a primary focus on LDL-C and with secondary focuses on the percentage of patients who reached the LDL-C targets and changes in the levels of RLP-C (remnant like particle cholesterol) and sd-LDL-C, two characteristic atherogenic risks of DM.ResultsThe reduction of LDL-C (%), the primary endpoint, differed significantly between the two groups (-24.6 in EAT vs. -10.9 in DST). In the analyses of the secondary endpoints, EAT treatment brought about significantly larger reductions in sd-LDL-C (-20.5 vs. -3.7) and RLP-C (-19.7 vs. +5.5). In total, 89.4% of the patients receiving EAT reached the optimized treatment goal compared to 51.0% of the patients receiving DST. The changes in TC (-16.3 vs. -6.3) and non-HDL-C (-20.7 vs. -8.3) differed significantly between the two groups.ConclusionEzetimibe added to high-potency statin (10 mg of atorvastatin or 1 mg of pitavastatin) was more effective than the intensified-dose statin (20 mg of atorvastatin or 2 mg of pitavastatin) treatment not only in helping T2DM patients attain more LDL-C reduction, but also in improving their atherogenic lipid profiles, including their levels of sd-LDL-C and RLP-C.We thus recommend the addition of ezetimibe to high-potency statin as a first line strategy for T2DM patients with insufficient statin response.Trial RegistrationThe UMIN Clinical Trials Registry UMIN000002593

Highlights

Patients with dyslipidemia complicated by diabetes are highly prone to cardiovascular disease and mortality [1, 2]
The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks
In the analyses of the secondary endpoints, EAT treatment brought about significantly larger reductions in sd-LDL-C (-20.5 vs. -3.7) and remnant-like particle cholesterol (RLP-C) (-19.7 vs. +5.5)

Summary

Introduction

Patients with dyslipidemia complicated by diabetes are highly prone to cardiovascular disease and mortality [1, 2]. Many guidelines for atherosclerotic diseases [3, 4] have supported the inclusion of patients with diabetes in the high-risk category, confirmed the benefits of LDLlowering therapy, and lowered the target value for prevention in these patients. Recent surveys have shown that the patients at the highest cardiovascular risk more often fail to achieve their therapeutic goal, especially diabetics [9]. The use of super-high-dose statin treatments to achieve LDL-C goals leads to more frequent side effects and more persistent cardiovascular risk. These circumstances evoke the demand for investigating the possibility and establishing alternative LDL-cholesterol-lowering treatments other than increasing in firstchoice statin doses. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks

Methods

Results

Discussion

Conclusion