Department of Internal Medicine, Seoul National University Hospital and Seoul National University.
Donga University Hospital.
J Atheroscler Thromb. 2021 Feb 1;28(2):124-136. doi: 10.5551/jat.55616. Epub 2020 Apr 24.
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.
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.
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.
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.
在一项前瞻性、随机、多国、开放、盲终点研究中，首次评估了普罗布考或普罗布考联合西洛他唑与他汀类药物对颈动脉内膜中层厚度（IMT）的长期影响。
将患有冠心病的高胆固醇血症患者随机分为三组，并接受研究药物治疗 3 年：单独使用他汀类药物的对照组；联合使用他汀类药物和普罗布考的普罗布考组；以及联合使用他汀类药物、普罗布考和西洛他唑的联合组。主要疗效终点是 3 年后颈动脉平均 IMT 的变化。生物标志物、主要不良心脑血管事件（MACCE）和安全性为次要终点。
281 例患者被随机分为三组。三组患者在 3 年内均显示颈动脉 IMT 明显消退，与基线相比。联合组在第 1 年时颈动脉平均 IMT 的减少明显大于对照组。然而，3 年后各组颈动脉平均 IMT 的变化无显著差异（对照组：-0.12±0.36mm；普罗布考组：-0.11 ±0.32mm；联合组：-0.16±0.38mm）。对照组 MACCE 较为频繁，但差异无统计学意义（对照组：10.8%；普罗布考组：4.4%；联合组：6.9%，p=0.35）。普罗布考和西洛他唑在长期治疗中耐受性良好，无严重与药物相关的不良反应。
在本研究中，与单独使用他汀类药物相比，普罗布考或普罗布考联合西洛他唑与他汀类药物并不能降低颈动脉 IMT。然而，目前标准他汀类药物治疗中基于普罗布考的治疗的临床结果可能需要进一步研究。
