Department of Rheumatology, Wirral University Teaching Hospital NHS Foundation Trust, Wirral, UK.
Rheumatology (Oxford). 2010 May;49(5):990-6. doi: 10.1093/rheumatology/keq003. Epub 2010 Feb 16.
The aim of this study was to test the hypothesis that statin therapy confers benefit on the microvasculature, including improving endothelial function, in patients with SSc.
This was a randomized, parallel group, double-blind study, with assessments at baseline, 4 and 8 weeks. Thirty-six patients were randomly assigned to receive 8 weeks treatment with atorvastatin 20 mg/day or placebo. The primary end-point was endothelial-dependent vasodilation, as assessed by response to iontophoresis with acetylcholine chloride (ACh) as measured by laser Doppler imaging. Secondary end-points included endothelial-independent vasodilation, microvascular structure as assessed by videocapillaroscopy, von Willebrand factor, high-sensitivity CRP and plasma cholesterol.
Eighteen patients were randomly assigned to atorvastatin and 18 to placebo. Eight weeks treatment resulted in no statistically significant differences in any of the outcome measures (other than cholesterol) between atorvastatin and placebo groups. The median area under the curve for ACh iontophoresis at baseline was 1569 perfusion units (PU).time in the atorvastatin group and 1450 PU.time in the placebo group, and at 8 weeks 2146 and 1822 PU.time, respectively. Mean difference (95% CI) at 8 weeks was 355 (-835, 1544) PU.time.
Atorvastatin 20 mg/day, given for 8 weeks, was not associated with changes in microvascular function or structure. The large variation in outcome scores means that it is not possible to rule out an effect on the basis of this trial. Future studies should be of longer duration and include patients with early disease who are unlikely to have irreversible structural vascular disease.
EudraCT, https://eudract.emea.europa.eu/, 2005-003775-21.
本研究旨在检验他汀类药物治疗是否有益于 SSc 患者的微血管，包括改善内皮功能这一假说。
这是一项随机、平行组、双盲研究，基线、4 周和 8 周时进行评估。36 名患者被随机分为阿托伐他汀 20mg/天组或安慰剂组，接受 8 周治疗。主要终点是通过激光多普勒成像测量的氯乙酰胆碱（ACh）离子电泳引起的内皮依赖性血管舒张反应。次要终点包括内皮非依赖性血管舒张、通过视频毛细血管镜评估的微血管结构、血管性血友病因子、高敏 C 反应蛋白和血浆胆固醇。
18 名患者被随机分配至阿托伐他汀组，18 名患者被分配至安慰剂组。8 周治疗后，阿托伐他汀组和安慰剂组在任何终点测量（除胆固醇外）均无统计学差异。基线时 ACh 离子电泳的曲线下面积中位数在阿托伐他汀组为 1569 灌注单位（PU）.time，在安慰剂组为 1450 PU.time，8 周时分别为 2146 和 1822 PU.time。8 周时的平均差值（95%CI）为 355（-835，1544）PU.time。
阿托伐他汀 20mg/天，连续使用 8 周，与微血管功能或结构的变化无关。由于终点评分的较大差异，因此无法根据本试验排除其对治疗的影响。未来的研究应延长研究时间，并纳入不太可能存在不可逆结构性血管疾病的早期疾病患者。
