The phosphodiesterase inhibitor cilostazol induces regression of carotid atherosclerosis in subjects with type2 diabetes mellitus


 Results from DAPC study

The phosphodiesterase inhibitor cilostazol induces
regression of carotid atherosclerosis in
subjects with type2 diabetes mellitus

Naoto Katakami, MD, PhD; Young-Seol Kim, MD, PhD;
Ryuzo Kawamori, MD, PhD; Yoshimitsu Yamasaki, MD, PhD

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 carotidintima-media thickening are unknown.

Methods and Results: To compare prevention by cilostazol and aspirin of progression of atherosclerosis, we conducteda 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 acilostazol-treated (100 to 200 mg/d) group. The changes in intima-media thickness of the common carotid artery duringa 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 A1c, theimprovements 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.

KEY WORDS: aspirin _ atherosclerosis _ carotid arteries _ diabetes mellitus _ intima-media thickness

Clinical Trial Registration: URL: Unique identifier: C000000215.

(Circulation. 2010;121:2584-2591.)