Combined Therapeutic Effect of Probucol and Cilostazol on Endothelial Function in Patients with Silent Cerebral Lacunar Infarcts and Hypercholesterolemia: A Preliminary Study

OBJECTIVE This study evaluated the efficacy of combined therapy with probucol and cilostazol on endothelial function in silent lacunar cerebral infarcts (SLCI) and mild hypercholesterolemia. SUBJECTS AND METHODS Flow-mediated vasodilatation (FMD) and nitroglycerin-induced vasodilatation (NMD) were measured before and after 4 weeks of combined therapy with probucol (500 mg/day) and cilostazol (200 mg/day) in 34 patients with a mean age of 72 ± 7 years (range 57-80 years) with SLCI, mild hypercholesterolemia (low-density lipoprotein cholesterol >100 mg/dl) and impaired endothelial function (FMD <6%). Patients were randomly allocated to one of the following two treatment groups: (1) aspirin (100 mg/day) with behavioral modifications, such as diet and/or exercise therapy (A group or control group, n = 17), and (2) probucol and cilostazol treatment (PC group, n = 17), also with behavioral modifications. RESULTS Although the baseline FMD was not different between the two treatment arms (2.7 ± 1.5 vs. 2.6 ± 1.5%, n.s.), the posttreatment FMD was significantly improved in the PC group (from 2.7 ± 1.5 to 3.5 ± 1.7%, p < 0.05) but not in the A group (from 2.6 ± 1.5 to 2.9 ± 1.4%, n.s.). No differences were observed between baseline and posttreatment NMD in either group. The effects of treatments on lipid profiles were more profound in the PC group. CONCLUSION Combined treatment with probucol and cilostazol resulted in subacute improvement in FMD/endothelial function in patients with SLCI with mild hypercholesterolemia. This combination therapy has the potential to reduce the risk of cardiovascular events via improvements in endothelial function and lipid profiles.