title: Cilostazol decreases cerebral arterial pulsatility in patients with mild white matter hyperintensities: subgroup analysis from the Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of Transcranial Doppler (ECLIPse) study.
abstract: BACKGROUND
  The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of the Transcranial Doppler (ECLIPse) study showed a significant decrease in the transcranial Doppler (TCD) pulsatility index (PI) with cilostazol treatment at 90 days after acute lacunar infarction. The aim of the present study was to perform a subgroup analysis of the ECLIPse study in order to explore the effect of cilostazol in acute lacunar infarction based on cerebral white matter hyperintensities (WMH) volume.
  
  
  METHODS
  The ECLIPse study was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated the difference between the efficacy of cilostazol and a placebo to reduce the PI in patients with acute lacunar infarction using serial TCD examinations. The primary outcome was changes in the PIs of the middle cerebral artery (MCA) and basilar artery at 14 and 90 days from the baseline TCD study. For this subgroup analysis, using semi-automated computerized software, the WMH volume was measured for those subjects for whom fluid-attenuated inversion recovery (FLAIR) images were available.
  
  
  RESULTS
  Of the 203 patients in eight hospitals in the ECLIPse study, 130 participants from six hospitals were included in this subgroup analysis. Cilostazol was given to 63 patients (48.5%) and placebo to 67 patients (51.5%). All baseline characteristics were well balanced across the two groups, and there were no significant differences in these characteristics except in the changes of PI from the baseline to the 90-day point. There was a significant decrease of TCD PIs at 90-day study from baseline in the cilostazol group (p = 0.02). The mean WMH volume was 11.57 cm(3) (0.13-68.45, median 4.86) and the mean MCA PI was 0.95 (0.62-1.50). The changes in PIs from the baseline to 14 days and to 90 days were 0.09 (-0.21 to 0.33) and 0.10 (-0.22 to 0.36). While there were no significant correlations between WMH volume and the changes in PIs, a trend of inverse correlation was observed between the WMH volume and the changes in PIs from the baseline to the 90-day point. For the subgroup analysis, the WMH volume was dichotomized based on its median value (4.90 cm(3)). Cilostazol decreased the TCD PIs significantly at the 90-day point in patients with WMH volumes ≤ 4.9 cm(3) (p = 0.002). Significant treatment effects were observed in the cilostazol group.
  
  
  CONCLUSIONS
  This study showed that cilostazol decreased cerebral arterial pulsatility in patients with WMH. Our findings indicate the unique effect of cilostazol in small vessel disease (SVD), especially in patients with mild WMH changes. Further clinical trials focusing on WMH volume and clinical outcomes are required to assess the unique efficacy of cilostazol in SVD.
authors.affiliation: Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine Seoul, Seoul, South Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Han
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Song
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Bushnell
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Lee
authors.forename: Seo Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Jun Hong
authors.initials: JH
authors.lastname: Lee
authors.forename: Gyu Sik
authors.initials: GS
authors.lastname: Kim
authors.forename: Ok-Joon
authors.initials: OJ
authors.lastname: Kim
authors.forename: Im-Seok
authors.initials: IS
authors.lastname: Koh
authors.forename: Jong Yun
authors.initials: JY
authors.lastname: Lee
authors.forename: Seung-Han
authors.initials: SH
authors.lastname: Suk
authors.forename: Sung Ik
authors.initials: SI
authors.lastname: Lee
authors.forename: Hyo Suk
authors.initials: HS
authors.lastname: Nam
authors.forename: Won-Joo
authors.initials: WJ
authors.lastname: Kim
authors.forename: Kyung-Yul
authors.initials: KY
authors.lastname: Lee
authors.forename: Joong Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Jeong Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000368:Aged; D001488:Basilar Artery / Q000000981:diagnostic imaging*; D000077407:Cilostazol; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000150:complications / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging*; D011673:Pulsatile Flow; D059409:Stroke, Lacunar / Q000150:complications / Q000188:drug therapy*; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial; D066127:White Matter / Q000473:pathology*
chemical_list: D013777:Tetrazoles; D000077407:Cilostazol