Abstract

BACKGROUND
Headache is frequently reported by patients using cilostazol, which is a potent inhibitor of platelet aggregation with vasodilatory effects, for preventing atherosclerotic disease. The aims of this study were to think out a dosing schedule for improving compliance on headache and to investigate the possible mechanisms of headache associated with atherosclerosis measured as carotid intimal-media thickness (IMT) in Korean diabetic patients. METHODS: We therefore randomized patients into three groups according to the different dosing regimens for 6 weeks (1) group 1; 50 mg once daily, followed by 50 mg twice daily, and then 100 mg twice daily or (2) group 2; 50 mg twice daily, followed by 100 mg twice daily or (3) group 3; 100 mg twice daily without titration. We evaluated severity of the headache by visual analog scaled (VAS) symptom score from zero to ten and measured carotid IMT using high resolution ultrasound. RESULTS: A total of 122 diabetic patients were analyzed. The mean values of age, sex, duration of diabetes, BMI, HbA1c, lipid profiles, blood pressure, and smoking were not different among three groups. The proportion of headache was significantly lower in group 1 than group 2 and 3 (26% vs. 48% and 51%, P < 0.05). The proportion of severe headache was significantly lower in group 1 than group 2 and 3 (3% vs. 19% , 27%, P < 0.05). Among patients who had headache, the proportion of severe headache was significantly lower in group 1 than group 3. (10% vs. 52%, P < 0.05). The VAS symptom score of headache was significantly lower in group 1 than group 3 (4.9+/-2.1 vs. 7.0+/-2.4, P < 0.05). The proportion of the discontinuation of medication due to headache was significantly lower in group 1 than other two groups (8% vs. 24% and 29%, P < 0.05). The patients who had discontinued medication due to headache had lower carotid IMT than in whom were tolerable (Mean carotid IMT; 0.65+/-0.12 vs. 0.77+/-0.16 mm, P < 0.01, Maximal carotid IMT; 0.80+/-0.17 vs. 0.94+/-0.23 mm, P < 0.01). The proportion of patients who had discontinued medication due to headache was significantly lower in group 1 than other two groups (8% vs. 24%, 29%, P < 0.05] CONCLUSION: Titration with an initially lower dose of cilostazol could be considered to reduce the proportion and severity of headache and thereby increase compliance. Atherosclerosis estimated as carotid IMT may contribute to the tolerability of cilostazol.

• Keywords: Carotid intimal-media thickness;Cilostazol;Diabetes mellitus;Dosing schedule;Headache