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We evaluated the plasma concentrations of platelet activation markers, microparticles and soluble adhesion molecules in patients with arteriosclerosis obliterans (ASO) and compared the beneficial effects of cilostazol alone and combination therapy of cilostazol and dipyridamole in these patients. There was a significant elevation of CD62P, CD63, PAC-1, annexin V, platelet-derived microparticles (PDMPs), sP-selectin, sE-selectin, sICAM-1 and sVCAM-1 in the ASO patients compared with the controls. Platelet aggregation was decreased by 2 weeks of cilostazol monotherapy in the ASO patients. Adding dipyridamole to the cilostazol therapy for 2 weeks further reduced platelet aggregation. While treatment with cilostazol alone reduced levels of CD62P, CD63, PAC-1, annexin V, PDMP, and sP-selectin, the combination therapy reduced these parameters further. While sE-selectin and cell adhesion molecules did not change significantly after 2 weeks of combination therapy, they exhibited a remarkable decrease after 16 weeks of combination treatment. These findings suggest that platelets are activated in ASO patients, and cilostazol is effective to reduce platelet activation. Furthermore, dipyridamole may potentiate the beneficial effect of cilostazol in ASO patients. Combination use of both drugs may help to prevent the onset of cardiovascular complications in patients with ASO by activated platelets and PDMP.
Nomura et al. (2004) studied this question.