The phosphodiesterase inhibitor cilostazol induces regression of carotid atherosclerosis in subjects with type 2 diabetes mellitus: principal results of the Diabetic Atherosclerosis Prevention by Cilostazol (DAPC) study: a randomized trial.

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 + or - 0.260 versus 0.059 + or - 0.275 mm, P<0.001; -0.042 + or - 0.274 versus 0.045 + or - 0.216 mm, P=0.003; -0.043 + or - 0.182 versus 0.028 + or - 0.202 mm, P=0.004; and -0.024 + or - 0.182 versus 0.048 + or - 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.