Cilostazol improves endothelial function in acute cerebral ischemia patients: a double-blind placebo controlled trial with flow-mediated dilation technique

BMC Neurol. 2017 Aug 29;17(1):169. doi: 10.1186/s12883-017-0950-y.

Abstract

Background: In order to evaluate the impact of cilostazol on endothelial function, we compared the changes of flow-mediated dilation (FMD) between aspirin and cilostazol groups in patients with acute cerebral ischemia.

Methods: Patients presenting with acute cerebral ischemic events were randomly assigned into aspirin (n = 40) or cilostazol (n = 40) group in a double-blinded manner. FMD was measured at baseline (T0) and 90 days (T1). We measured L-arginine at baseline (a precursor of biologically active nitric oxides). Serious and non-serious adverse events were described.

Results: Despite no difference in the baseline FMD values (p = 0.363), there was a significant increase of FMD values in cilostazol group (7.9 ± 2.4 to 8.9 ± 2.3%, p = 0.001) and not in aspirin group (8.5 ± 2.6 to 9.3 ± 2.8%, p = 0.108). In the multiple regression analysis performed in cilostazol group, serum L-arginine levels were inversely correlated with FMD at T1 (ß = -0.050, SE: 0.012, p < 0.001) with age, total cholesterol levels, and C-reactive protein as confounders. While T0 FMD values in both aspirin and cilostazol groups did not show any correlation with serum L-arginine levels, the correlation is restored in the cilostazol group at T1 (r = 0.467, p = 0.007), while such is not shown in the aspirin group. There was no difference of serious adverse events between the two groups (p = 0.235). Adverse events were more common in the cilostazol group (35/40 vs. 25/40, p = 0.010), due to frequent headaches (14/40 vs. 3/30, p = 0.003) which was well tolerated.

Conclusion: Cilostazol improved endothelial function in acute cerebral ischemia patients. It also restored an inverse correlation between 3-month FMD and baseline L-arginine levels.

Trial registration: NCT03116269 , 04/12/2017, retrospectively registered.

Keywords: Arginine; Cerebral infarction; Cilostazol; Endothelium; Transient ischemic attack.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Arginine / metabolism
  • Aspirin / therapeutic use*
  • Brain Ischemia / drug therapy*
  • C-Reactive Protein / metabolism
  • Cilostazol
  • Dilatation
  • Double-Blind Method
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Tetrazoles / therapeutic use*

Substances

  • Tetrazoles
  • C-Reactive Protein
  • Arginine
  • Cilostazol
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT03116269