Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial

Abstract

Background and Purpose: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. Methods: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. Results: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02–0.89]). Conclusions: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01932203.

Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease

“…However, sex differences in CMBs are not well-known. In this study, we aimed to explore the impact of sex on the progression of CMBs using longitudinal data from the CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) trial ( 14 ).…”

Antiplatelets and Vascular Dementia: A Systematic Review

“…They also examined its effect on the number of lacunes and cerebral microbleeds. Although they found that there was no significant difference between cilostazol and aspirin on white matter hyperintensities, they did note that cilostazol does significantly reduce the chance of ischemic cerebrovascular injury relative to aspirin [ 46 ]. White matter hyperintensities are a relatively new biomarker being investigated in cerebral small vessel diseases and, in general, cerebrovascular pathologies.…”

“…Inclusion and exclusion criteria were applied and only relevant research works regarding our research question were considered. A total of 35 articles were kept ( Figure 1 ) [ 12 – 46 ].…”

“…When compared to warfarin, edoxaban and rivaroxaban had a decreased risk of dementia. Kim et al [46] Korea Cilostazol (n � 127) versus aspirin (n � 129)…”

“…Recently, cilostazol has also been introduced as part of the management for cerebral small vessel diseases. Kim et al (2021) investigated the use of cilostazol for reducing white matter changes due to lacunar infarction relative to aspirin.…”