The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus

Abstract

Background— Antiplatelet drugs are effective in preventing recurrence of atherosclerosis in type 2 diabetic patients. However, the efficacy and usefulness of 2 different antiplatelet drugs, aspirin and cilostazol, in the progression of carotid intima-media thickening are unknown. Methods and Results— To compare prevention by cilostazol and aspirin of progression of atherosclerosis, we conducted a prospective, randomized, open, blinded end point study in 4 East Asian countries. A total of 329 type 2 diabetic patients suspected of peripheral artery disease were allocated to either an aspirin-treated (81 to 100 mg/d) group or a cilostazol-treated (100 to 200 mg/d) group. The changes in intima-media thickness of the common carotid artery during a 2-year observation period were examined as the primary end point. The regression in maximum left, maximum right, mean left, and mean right common carotid artery intima-media thickness was significantly greater with cilostazol compared with aspirin (−0.088±0.260 versus 0.059±0.275 mm, P <0.001; −0.042±0.274 versus 0.045±0.216 mm, P =0.003; −0.043±0.182 versus 0.028±0.202 mm, P =0.004; and −0.024±0.182 versus 0.048±0.169 mm, P <0.001). In a regression analysis adjusted for possible confounding factors such as lipid levels and hemoglobin A 1c , the improvements in common carotid artery intima-media thickness with cilostazol treatment over aspirin treatment remained significant. Conclusions— Compared with aspirin, cilostazol potently inhibited progression of carotid intima-media thickness, an established surrogate marker of cardiovascular events, in patients with type 2 diabetes mellitus. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: C000000215.