Effect of Probucol and/or Cilostazol on Carotid Intima Media Thickness in Patients with Coronary Heart Disease: A Randomized, Multicenter, Multinational Study

• Published in: Journal of Atherosclerosis and Thrombosis 2021/02/01, Vol.28(2), pp.124-136
• Main Authors: Kang, Hyun-Jae, Kim, Moo Hyun, Sung, Jidong, Kim, Sang-Hyun, Kim, Cheol-Ho, Park, Jeong Euy, Ge, Junbo, Oh, Byung-Hee, On behalf of IMPACT on IMT investigators
• Format: Article
• Language: English
• Subjects: Carotid intima media thickness; Cilostazol; Coronary artery disease; Original; Probucol
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.55616

Aim: In a prospective randomized multinational open blinded endpoint study, the long-term effects of probucol or probucol and cilostazol with statin on carotid mean intima media thickness (IMT) were evaluated for the first time. Methods: Hypercholesterolemic patients with coronary artery disease were randomized to three groups and received study drugs for 3 years: the control with statin alone; the probucol group with statin and probucol; and the combo group with statin, probucol, and cilostazol. Primary efficacy endpoint was changes of mean carotid IMT at 3 years. Biomarkers, major adverse cerebro-cardiovascular events (MACCEs) and safety were secondary endpoints. Results: Two hundred eighty-one patients were randomized into three groups. All three groups showed significant regression of carotid IMT at 3 years compared with baseline. Decrease in mean carotid IMT was significantly greater in the combo group than in the control group at 1 year. However, there were no significant differences in changes of mean carotid IMT between groups at 3 years (control; −0.12±0.36 mm vs. probucol; −0.11 ±0.32 mm vs. combo; −0.16±0.38 mm). MACCEs were frequent in the control group, but the difference was not significant (control; 10.8% vs. probucol; 4.4% vs. combo; 6.9%, p=0.35). Probucol and cilostazol were well tolerated in long-term treatment without serious drug-related adverse reactions. Conclusion: Probucol or probucol and cilostazol with statin did not reduce carotid IMT in comparison with statin alone in this study. However, the clinical outcome of probucol-based treatment with current standard statin treatment may need further studies.