Effectiveness of Cilostazol in Patients with Intermittent Claudication

INTRODUCTION: Despite the intensive study of the pathophysiology, molecular and cellular mechanisms of atherosclerosis, the development and introduction of a number of new treatment methods, to date, the disease of the arteries of the lower extremities is one of the most pressing problems of modern vascular surgery and medicine in general. AIM: To evaluate the influence of cilostazol on the functional status of endothelium and pain-free walking distance in patients with lower limb artery diseases of atherosclerotic etiology. MATERIALS AND METHODS: The study was performed on 80 patients with obliterating atherosclerosis of lower limb arteries. Depending on the type of the given conservative therapy, the patients were divided to two groups. Group A (n = 40) included patients who received the baseline therapy in accordance with National recommendations on managing patients with peripheral artery diseases, and also medical drug Aducil® (cilostazol) 100 mg 1 tablet two times a day. Group В (n = 40) included patients who received only baseline therapy in accordance with National recommendations on managing patients with peripheral artery diseases. From all the patients, venous blood samples were taken for determining a number of markers of the endothelial dysfunction: endothelial nitric oxide synthase, prostacyclin, endothelin-1, interleukine-6. RESULTS: In 6 and 12 months after the start of the treatment, the level of endothelial nitric oxide synthase was reliably higher in group А patients (6 months — 12.91 (11.23–14.57) ng/ml; 12 months — 13.86 (12.42–16.25) ng/ml) in comparison with group В (6 months — 11.62 (8.63–16.73) ng/ml; 12 months — 11.76 (8.32–18.43) ng/ml) (р < 0.001). The level of prostacyclin was statistically significantly higher in group А after 6 months (group А — 18,532.88 (17,458.85–20,905.71) ng/ml; group В — 17,592.5 (15,542.56–19,721.52) ng/ml) and 12 months (group А — 18,452.27 (17,567.31–20,780.05) ng/ml; group В — 17,013.05 (15,090.1–19,517.58) ng/ml) in comparison with group В (р < 0.05). After 1 month from the start of treatment, the level of interleukin-6 was lower in group А (group А — 2.8 (2.23–3.4) ng/ml; group В — 3.65 (2.65–4.7) ng/ml), in 3 months — (group А — 2.4 (2–2.95) ng/ml; group В — 3.6 (2.55–4.5) ng/ml), 6 months (group А — 2.15 (1.73–2.88) ng/ml; group В — 3.45 (2.73–4.4) ng/ml), and 12 months (group А — 2.2 (1.93–2.95) ng/ml; group В — 3.3 (2.6–4.2) ng/ml) in comparison with group В (р < 0.001). No statistically significant difference in the levels of endothelin-1 was seen between group А and group В (p > 0.05). The analysis of the pain-free walking distance after 1 month (group А — 450 (436.25–487.5) m; group В — 250 (242.5–280) m), 3 months (group А — 455 (450–507.5) m; group В — 250 (250–277.5) m), 6 months (group А — 440 (430–487.5) m; group В — 235 (220–250) m), and 12 months (group А — 425 (410–465) m; group В — 210 (190–220) m) showed statistically reliable increase in the parameter in group А in comparison with group В (р < 0.001). Based on the results of USDS, the patients of group А showed statistically significant increase in the ankle-brachial index in 1, 3, 6 months (group А — 0.7 (0.7–0.7); group В — 0.6 (0.6–0.6)) and 12 months (group А — 0.7 (0.6–0.7); group В — 0.6 (0.5–0.6)) after the start of treatment in comparison with group В (р < 0.001). CONCLUSIONS: Treatment with cilostazol stimulates increase of the level of endothelial nitric oxide synthase and prostacyclin, and also promotes decrease in the level of interleukin-6. Cilostazol reliably increases pain-free walking distance and the ankle-brachial index.