title: A randomized, open-label, multicentre study to evaluate plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus and arteriosclerosis obliterans when treated with Probucol and Cilostazol.
abstract: OBJECTIVE
  To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus (T2DM) and arteriosclerosis obliteran (ASO) when treated with Probucol plus Cilostazol in combination and individually.
  
  
  METHODS
  In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks.
  
  
  RESULTS
  Of the 200 randomized patients, 165 for per-protocol and 160 for the safety (QTc intervals) were set, respectively. Probucol significantly reduced total cholesterol (P < 0.001), low-density lipoprotein cholesterol (LDL-C), (P = 0.01), and high-density lipoprotein cholesterol (HDL-C) (P < 0.001) compared with conventional therapy. Cilostazol was effective in increasing HDL-C (P = 0.002) and reducing triglycerides levels (P < 0.01) compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein (Ox-LDL, P = 0.065). No significant effects on the majority of the remaining biomarkers were found across the treatment groups.
  
  
  CONCLUSIONS
  We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.
authors.affiliation: Department of Endocrinology, Peking University First Hospital, No.7 of Xishiku Street, Xicheng District, Beijing 100034, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Ma
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Guo
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Xiao
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Guo
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Lv
authors.forename: Quan-Min
authors.initials: QM
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
keywords: Atherosclerosis; Biomarkers; Cilostazol; Combination treatment; Probucol; Synergetic effect