Cilostazol Attenuates Spontaneous Microaggregation of Platelets in Type 2 Diabetic Patients With Insufficient Platelet Response to Aspirin

P revention of cardiovascular disease is an important therapeutic goal in patients with type 2 diabetes melli-tus (1). Although a low dose of aspirin is recommended for this purpose, some patients were resistant to aspirin (2). We previously reported that spontaneous mi-croaggregation of platelets (SMAPs) formed under no stimulation with exoge-nous agonists were frequently observed in type 2 diabetic patients (3,4) and a considerable number of patients receiving aspirin still showed SMAP formation (4). The aim of the current study was to investigate whether a switch from aspirin to another antiplatelet drug could improve an insufficient platelet response to aspirin in diabetic patients. This was an open-label, single-arm, uncontrolled trial of antiplatelet treatment with 200 mg cilostazol daily (a phosphodiesterase III inhibitor) as an alternative to aspirin in 24 Japanese type 2 diabetic patients who persistently showed the inadequate SMAP formation despite treatment with a low dose of aspirin (22 patients with 100 mg aspirin daily and 2 with 81 mg aspirin daily) for at least 1 year. Patients receiving antiplatelet drugs other than aspirin were excluded. Assessments included the changes in SMAP formation as well as platelet expression of active glycoprotein IIb/IIIa and P-selectin at 2 months compared with baseline. These were measured as previously described (4). After ethics committee approval, written informed consent was obtained from all participants. Twenty-three of 24 patients (65% men; mean age 71 years and mean HbA 1c 7.6% [60 mmol/mol]) completed the study. There was no significant difference in clinical parameters comparing the baseline time point with the 2-month time point. As shown in Fig. 1, the degree of SMAP formation was significantly reduced after changing from aspirin to cilostazol (0.32 [interquartile range 0.15–0.48] at baseline, 0.13 [0.00–0.26] at 1 month, and 0.11 [0.00–0.22] at 2 months, P 5 0.001 by the Friedman test]. This inhibitory effect by cilostazol was observed at 1 month compared with baseline, and this difference persisted at the 2-month time point. At 2 months after the administration of cilostazol, 17 patients (74%) showed a reduction in SMAP formation of .50% compared with baseline. Further, SMAP formation completely disappeared in seven of these patients.002) were also significantly lower at the 2-month time point compared with baseline. Adverse events (headache and palpitations) occurred in two patients, one of whom discontinued the study. No major bleeding events occurred. This study demonstrated that anti-platelet therapy with cilostazol significantly attenuated SMAP formation and …