高剂量阿托伐他汀治疗外周动脉疾病（PAD）：对内皮功能、内膜中层厚度及PAD局部进展的影响。一项开放性随机对照试验。

High-dose atorvastatin in peripheral arterial disease (PAD): effect on endothelial function, intima-media-thickness and local progression of PAD. An open randomized controlled pilot trial.

作者信息

Spring Silviana, Simon Roger, van der Loo Bernd, Kovacevic Tamara, Brockes Christiane, Rousson Valentin, Amann-Vesti Beatrice, Koppensteiner Renate

机构信息

Clinic of Angiology, Department of Medicine, University Hospital Zurich, Switzerland.

出版信息

Thromb Haemost. 2008 Jan;99(1):182-9. doi: 10.1160/TH07-04-0265.

DOI:10.1160/TH07-04-0265

PMID:18217152

Abstract

Beneficial effects of aggressive lipid-lowering with high-dose atorvastatin (80 mg/day) have been demonstrated in patients with coronary and cerebrovascular disease. The impact of such a therapy in patients with peripheral arterial disease (PAD) is less known so far. Here we studied the effects of high-dose atorvastatin on brachial artery endothelial function, common carotid intima-media thickness (IMT) and local progression of PAD in these patients. One hundred of 500 patients screened with documented PAD were randomly assigned to receive 80 mg of atorvastatin daily for six months or to continue on conventional medical treatment. Ninety-six percent of patients in the control group were on standard statin treatment. High resolution B-mode ultrasonography was used to study brachial artery flow-mediated dilation (FMD), IMT and ankle-brachial index (ABI) at baseline and at six months. FMD and IMT at baseline and at six months were 4.1 (0.06-8.6) versus 5.0 (0.76 vs. 8.1) %, p = 0.96, and 0.76 (0.66-0.82) versus 0.73 (0.63-0.81) mm, p = 0.41, respectively, in the atorvastatin group, and 2.66 (-1.9-6.9) versus 3.65 (0.0-8.6)%, p = 0.02, and 0.78 (0.71-0.90) versus 0.77 (0.70-0.90) mm, p = 0.48, in the control group. ABI at baseline and at six months was not different in either group. LDL cholesterol was reduced from 2.53 (2.21-3.28) to 1.86 (1.38-2.29) mM (p < 0.0001) in the atorvastatin group, whereas levels remained stable in the control group [2.38 (1.94-3.16) vs. 2.33 (1.82-2.84) mM, p = 0.61]. Major adverse cardiovascular events occurred in 2.1% in the atorvastatin group and 1.9% in the control group (p = 0.61). In conclusion, in this pilot trial aggressive lipid-lowering with 80 mg of atorvastatin daily for six months had no effect on brachial artery FMD in patients with PAD. IMT and ABI were also similar in patients with and without high-dose atorvastatin at six months.

摘要

高剂量阿托伐他汀（80毫克/天）积极降脂治疗对冠心病和脑血管病患者的有益作用已得到证实。迄今为止，这种治疗对外周动脉疾病（PAD）患者的影响尚鲜为人知。在此，我们研究了高剂量阿托伐他汀对这些患者肱动脉内皮功能、颈总动脉内膜中层厚度（IMT）以及PAD局部进展的影响。在500例经记录确诊为PAD的筛查患者中，100例被随机分配，一组每日接受80毫克阿托伐他汀治疗六个月，另一组继续接受常规药物治疗。对照组96%的患者接受标准他汀类药物治疗。使用高分辨率B型超声在基线及六个月时研究肱动脉血流介导的舒张功能（FMD）、IMT和踝臂指数（ABI）。阿托伐他汀组基线及六个月时的FMD分别为4.1（0.06 - 8.6）%和5.0（0.76对8.1）%，p = 0.96；IMT分别为0.76（0.66 - 0.82）毫米和0.73（0.63 - 0.81）毫米，p = 0.41。对照组基线及六个月时的FMD分别为2.66（ - 1.9 - 6.9）%和3.65（0.0 - 8.6）%，p = 0.02；IMT分别为0.78（0.71 - 0.90）毫米和0.77（0.70 - 0.90）毫米，p = 0.48。两组在基线及六个月时的ABI均无差异。阿托伐他汀组低密度脂蛋白胆固醇从2.53（2.21 - 3.28）毫摩尔降至1.86（1.38 - 2.29）毫摩尔（p < 0.0001），而对照组水平保持稳定[2.38（1.94 - 3.16）对2.33（1.82 - 2.84）毫摩尔，p = 0.61]。阿托伐他汀组主要不良心血管事件发生率为2.1%，对照组为1.9%（p = 0.61）。总之，在这项初步试验中，对于PAD患者，每日80毫克阿托伐他汀积极降脂治疗六个月对肱动脉FMD无影响。六个月时，接受和未接受高剂量阿托伐他汀治疗的患者IMT和ABI也相似。