Comparison of the Effect of Cilostazol with Aspirin on Circulating Endothelial Progenitor Cells and Small-Dense LDL Cholesterol in Diabetic Patients with Cerebral Ischemia: A Randomized Controlled Pilot Trial

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Aim: A recent clinical trial showed the preventive effect of cilostazol on cerebrovascular diseases. We compared the effects of cilostazol with aspirin on circulating endothelial progenitor cells (EPCs), a surrogate marker for cardiovascular disease, and lipid metabolism in a randomized controlled trial (UMIN000000537).
Methods: Forty-nine diabetic outpatients with leukoaraiosis or asymptomatic old cerebral infarction were enrolled in the study with written informed consent. They were randomly assigned to a cilostazol (200 mg daily, n= 24) or aspirin group (100 mg daily, n= 25), and followed for 16 weeks. Changes in circulating CD34⁺ CD45^low CD133⁺ VEGFR2⁺ EPCs (ΔEPC) were a primary endpoint. Changes in CD34⁺ CD45^low CD133⁺ progenitor cells (ΔPC), p-selectin-positive platelet, platelet-monocyte binding measured by flow cytometry, LDL-, HDL-, small dense LDL (sdLDL)-cholesterol and triacylglycerol were the secondary endpoints.
Results: Twenty patients in each group completed the study. ΔEPC were significantly higher in the cilostazol group than aspirin group at 16 weeks, while ΔPC were already significantly higher at 4 weeks in the cilostazol group. Changes in p-selectin-positive platelets and platelet-monocyte binding were similar in both groups. The cilostazol group showed significantly less sdLDL- and higher HDL-cholesterol than the aspirin group at both 4 and 16 weeks. ΔEPC were significantly and inversely correlated with changes of sdLDL, while positively with those of HDL. Analysis of covariance showed that a significant relation of ΔEPCs with cilostazol treatment was confounded by changes in HDL- and sdLDL-cholesterol.
Conclusion: Cilostazol increases circulating EPCs and decreases small-dense LDL in diabetic patients with cerebral ischemia.