Abstract
Background: Impairment of endothelial function is associated with atherosclerosis. Cilostazol is an antiplatelet drug that inhibits phosphodiesterase III, and has the potential to improve endothelial function. The prospective, open-label, randomized trial to evaluate the safety and efficacy of dual antiplatelet therapy involving cilostazol for secondary ischemic stroke prevention is ongoing (The Cilostazol Stroke Prevention Study for Antiplatelet Combination; CSPS.com) (Int J Stroke Vol 10, Feb 2015, 253). Objective: The purpose of this study was to clarify the effect of cilostazol in addition to clopidogrel on endothelial function in patients with ischemic stroke. Material and Methods: This study was a sub-study of CSPS.com, and registered in clinical trial (UMIN 000026672). The subjects were enrolled in our hospital from ischemic stroke patients taking clopidogrel after 8-180 days. They were randomly assigned into two groups, one with adding cilostazol on clopidogrel (CIL group), and other without cilostazol (Control group). Endothelial function was evaluated at enrollment and 6 months later, using the Flow Mediated Dilation (FMD) test of the brachial artery under blindness. Endothelial function was expressed as percent increase of brachial vessel diameter (%FMD) after interruption of blood flow with mechanical compression for five minutes. We also measured the plasma levels of inflammatory markers (highly sensitive C-reactive protein, interleukin 6, intercellular adhesion molecule-1, thrombomodulin) at enrollment and 6 months later. The ANOVA was used for statistical analysis. Results: Total 29 subjects (Control group 16, CIL group 13) were enrolled. The mean age of subjects was 71.2±8.6 years old, and 81.3% were males. The baseline %FMD was similar between Control group (4.60±0.62%) and CIL group (4.68±0.69%). At 6 months, %FMD did not change in Control group, but %FMD significantly improved in CIL group (p<0.01). There was no significant change in plasma levels of any inflammatory markers in both groups. Conclusion: This study showed that the %FMD significantly increased by adding cilostazol to clopidogrel in patients with ischemic stroke. Cilostazol may improve endothelial dysfunction independent of anti-inflammatory action.
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