PLoS ONE (Jan 2015)

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

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

DOI
https://doi.org/10.1371/journal.pone.0138332
Journal volume & issue
Vol. 10, no. 9
p. e0138332

Abstract

Read online

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.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.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.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.The UMIN Clinical Trials Registry UMIN000002593.