title: Effect of Ezetimibe on LDL-C Lowering and Atherogenic Lipoprotein Profiles in Type 2 Diabetic Patients Poorly Controlled by Statins.
abstract: BACKGROUND
  There 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.
  
  
  METHODS
  Lipid 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Ezetimibe 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.
  
  
  BACKGROUND
  The UMIN Clinical Trials Registry UMIN000002593.
authors.affiliation: Toho University Ohashi Medical Center, Department of Diabetes and Metabolism, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Tokyo Teishin Hospital, Division of Endocrinology and Metabolism Department of Internal Medicine, Tokyo, Japan.
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Kawamura
authors.affiliation: Jichi Medical University, Department of Medical Informatics / Cardiology, Tochigi, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Kohro
authors.affiliation: Yokohama Rosai Hospital, Department of Endocrinology and Metabolism, Kanagawa, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Omura
authors.affiliation: Yokohama City Minato Red Cross Hospital, Department of Internal Medicine, Kanagawa, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Kudanzaka Hospital, Department of Internal Medicine, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ashidate
authors.affiliation: Tokyo Metropolitan Health Medical Treatment Corporation Toshima Hospital, Department of Endocrinology and Metabolism, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Horiuchi
authors.affiliation: Toho University Ohashi Medical Center, Department of Cardiology, Tokyo, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Hara
authors.affiliation: Tokyo Koseinenkin Hospital, Department of Internal Medicine, Tokyo, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sekine
authors.affiliation: Tokyo Kyosai Hospital, Department of Internal Medicine, Tokyo, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Chin
authors.affiliation: Tokyo Metropolitan Tama Medical Center, Department of Internal Medicine, Tokyo, Japan.
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Tsujino
authors.affiliation: Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hiyoshi
authors.affiliation: Sanraku Hospital, Life-style related Disease Clinic, Tokyo, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Tagami
authors.affiliation: Kagawa Nutrition University, Nutrition Clinic, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Toranomon Hospital, Department of Endocrinology and Metabolism, Tokyo, Japan.
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Kashiwa City Hospital, Internal Medicine, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inazawa
authors.affiliation: Showa University School of Medicine, Department of Medicine Division of Diabetes Metabolism and Endocrinology, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirano
authors.affiliation: The University of Tokyo Hospital, Clinical Research Support Center, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Toho University Ohashi Medical Center, Department of Diabetes and Metabolism, Tokyo, Japan; Mitsui Memorial Hospital, Division of Diabetes and Metabolism, Tokyo Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Shiba
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors* / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D000069438:Ezetimibe / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe