Cilostazol Reduces PAC-1 Expression on Platelets in Ischemic Stroke

BACKGROUND AND PURPOSE Cilostazol, a phosphodiesterase III inhibitor, is known to be a useful antiplatelet agent that inhibits the progression of atherosclerosis in ischemic stroke. This study investigated the effects of combining cilostazol with aspirin on the expressions of P-selectin and PAC-1 on activated platelets in acute ischemic stroke. METHODS We analyzed 70 patients with acute ischemic stroke (<72 hrs of an ischemic event). The daily intake was 100 mg of aspirin in 37 patients and 100 mg of aspirin plus 200 mg of cilostazol in 33 patients. The expressions of P-selectin and PAC-1 on activated platelets were measured on the day of admission and 5 days later. We also evaluated the clinical progression using the National Institutes of Health Stroke Scale (NIHSS) at the same times. RESULTS After 5 days the extent of PAC-1 expression on activated platelets was significantly lower for combined aspirin and cilostazol treatment (61.0+/-19.3%, p=0.008; mean+/-standard deviation) than the baseline level (70.9+/-12.9%), but did not differ between aspirin alone (66.0 +/-19.0%) and baseline (70.1+/-15.7%). The expression of P-selectin did not differ between combined aspirin and cilostazol treatment and baseline. The clinical progression did not differ between the two groups, as indicated by the absence of significant changes on the NIHSS in the acute period. CONCLUSIONS This study found that the combined regimen of aspirin and cilostazol exerts the beneficial effect of reducing PAC-1 activity on activated platelets in acute ischemic stroke. However, the clinical outcome of this regimen was no better than that of the aspirin-only regimen. Therefore, further detailed studies of the possible clinical benefits of cilostazol in acute ischemic stroke are needed.