Departamento de Enfermedades Cardiovasculares, Facultad de Medicina, P. Universidad Católica de Chile, Santiago, Chile.
J Heart Lung Transplant. 2011 Apr;30(4):408-13. doi: 10.1016/j.healun.2010.10.003. Epub 2010 Dec 8.
Increased oxidative stress in heart failure (HF) leads to inflammation and endothelial dysfunction (ED). Both statins and allopurinol have known anti-oxidant properties, but their utility in HF has not been fully assessed.
This investigation was a prospective, double-blind, double-dummy study, performed between March 2007 and June 2009. Seventy-four HF patients, with New York Heart Association (NYHA) Class II or III status and left ventricular ejection fraction (LVEF) <40%, were included. Patients received placebo during 4 weeks and were then randomized to receive 4 weeks of either atorvastatin 20 mg/day plus placebo (ATV+PLA group) or atorvastatin 20 mg/day orally plus allopurinol 300 mg/day orally (ATV+ALLO group). Malondialdehyde (MDA), extracellular superoxide dismutase (ecSOD) activity and uric acid (UA) levels, among others, were determined at baseline and after 4 weeks of treatment. ED was assessed by flow-dependent endothelial-mediated vasodilation (FDD), and functional capacity by 6-minute walk test (6MWT).
Thirty-two patients were randomized to ATV+PLA and 38 to ATV+ALLO. Mean age was 59 ± 2 years, 82% were male, and 22% had an ischemic etiology. Hypertension was present in 60% and diabetes in 15% of those studied. No significant differences were observed between baseline measurements and after placebo. After 4 weeks of treatment, both groups showed a significant decrease on MDA (0.9 ± 0.1 to 0.8 ± 0.1 and 1.0 ± 0.5 to 0.9 ± 0.1 μmol/liter, p = 0.88), UA (7.4 ± 0.4 to 6.8 ± 0.3 and 7.2 ± 0.4 to 5.0 ± 0.3 mg/dl, p < 0.01) and FDD (3.9 ± 0.2% to 5.6 ± 0.4% and 4.6 ± 0.3% to 7.1 ± 0.5%, p = 0.07) with increased ecSOD activity (109 ± 11 to 173 ± 13 and 98 ± 10 to 202 ± 16, U/ml/min, p = 0.41) and improved 6MWT (447 ± 18 to 487 ± 19 and 438 ± 17 to 481 ± 21 m, p = 0.83), with all values for ATV+PLA and ATV+ALLO, respectively; p-values are for comparison between groups after treatment.
Short-term ATV treatment in heart failure (HF) patients reduces oxidative stress and improves FDD and functional capacity. These beneficial effects are not strengthened by the addition of allopurinol.
心力衰竭（HF）中氧化应激的增加会导致炎症和内皮功能障碍（ED）。他汀类药物和别嘌呤醇都具有已知的抗氧化特性，但它们在 HF 中的应用尚未得到充分评估。
这是一项前瞻性、双盲、双模拟研究，于 2007 年 3 月至 2009 年 6 月进行。纳入了 74 名纽约心脏协会（NYHA）II 或 III 级且左心室射血分数（LVEF）<40%的 HF 患者。患者在 4 周内接受安慰剂治疗，然后随机分为阿托伐他汀 20mg/天加安慰剂（ATV+PLA 组）或阿托伐他汀 20mg/天加别嘌呤醇 300mg/天（ATV+ALLO 组）。在基线和治疗 4 周后，测定丙二醛（MDA）、细胞外超氧化物歧化酶（ecSOD）活性和尿酸（UA）等水平。ED 通过血流依赖性内皮介导的血管舒张（FDD）评估，功能能力通过 6 分钟步行试验（6MWT）评估。
32 名患者被随机分配至 ATV+PLA 组，38 名患者被随机分配至 ATV+ALLO 组。平均年龄为 59±2 岁，82%为男性，22%有缺血性病因。60%的患者有高血压，15%的患者有糖尿病。基线测量值和安慰剂治疗后无显著差异。治疗 4 周后，两组 MDA（0.9±0.1 至 0.8±0.1 和 1.0±0.5 至 0.9±0.1μmol/l，p=0.88）、UA（7.4±0.4 至 6.8±0.3 和 7.2±0.4 至 5.0±0.3mg/dl，p<0.01）和 FDD（3.9±0.2%至 5.6±0.4%和 4.6±0.3%至 7.1±0.5%，p=0.07）均显著下降，ecSOD 活性（109±11 至 173±13 和 98±10 至 202±16，U/ml/min，p=0.41）和 6MWT（447±18 至 487±19 和 438±17 至 481±21 m，p=0.83）均有改善，分别为 ATV+PLA 和 ATV+ALLO 组的所有值；p 值是治疗后两组间的比较。
短期阿托伐他汀治疗心力衰竭（HF）患者可降低氧化应激水平，改善 FDD 和功能能力。添加别嘌呤醇并不能增强这些有益作用。
