SPARCL试验中高剂量阿托伐他汀对中风或短暂性脑缺血发作患者肾功能的影响。
Effect of high-dose atorvastatin on renal function in subjects with stroke or transient ischemic attack in the SPARCL trial.
作者信息
Amarenco Pierre, Callahan Alfred, Campese Vito M, Goldstein Larry B, Hennerici Michael G, Messig Michael, Sillesen Henrik, Welch K Michael A, Wilson Daniel J, Zivin Justin A
机构信息
Department of Neurology and Stroke Center, Paris-Diderot Sorbonne University, Paris, France (P.A.); Department of Neurology, Vanderbilt University, Nashville, TN (A.C.); Division of Nephrology and Hypertension Center, USC/Keck School of Medicine, Los Angeles, CA (V.M.C.); Department of Neurology, Duke University Medical Center, Durham, NC (L.B.G.); Department of Neurology, Universitat Heidelberg, Mannheim, Germany (M.G.H.); Pfizer Inc, New York, NY (M.M., D.J.W.); Department of Vascular Surgery, University of Copenhagen, Copenhagen, Denmark (H.S.); Office of the President, Rosalind Franklin University, Chicago, IL (K.M.A.W.); and Department of Neurology, University of California, San Diego (J.A.Z.).
出版信息
Stroke. 2014 Oct;45(10):2974-82. doi: 10.1161/STROKEAHA.114.005832. Epub 2014 Aug 21.
BACKGROUND AND PURPOSE
Higher low-density lipoprotein cholesterol is associated with more rapid chronic kidney disease progression; reduction in cholesterol with statins, in conjunction with statins' pleiotropic effects, such as decreasing inflammation, may be renoprotective. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial assessed the effect of statin treatment on the risk of nonfatal and fatal stroke in subjects with a noncardioembolic stroke or transient ischemic attack, no known coronary heart disease, and low-density lipoprotein cholesterol between 2.6 and 4.9 mmol/L (100-190 mg/dL).
METHODS
We explored the effect of randomization to atorvastatin 80 mg/d or placebo on the change in estimated glomerular filtration rate (eGFR; using the 4-component Modification of Diet in Renal Disease Study equation) in SPARCL subjects (n=4731) with (eGFR, <60 mL/min per 1.73 m2; n=3119) and without (eGFR, ≥60 mL/min per 1.73 m2; n=1600) chronic kidney disease overall and by glycemic status at baseline.
RESULTS
Mean baseline eGFR was similar between treatment groups (65.5±0.26 versus 65.6±0.26 mL/min per 1.73 m2 atorvastatin versus placebo; 33% versus 34% had chronic kidney disease, respectively; P=0.55). After 60 months, eGFR increased 3.46±0.33 mL/min per 1.73 m2 in those randomized to atorvastatin versus 1.42±0.34 mL/min per 1.73 m2 in those randomized to placebo (P<0.001) independent of baseline renal function. In the subgroup with diabetes mellitus at randomization, eGFR increased 1.12±0.92 mL/min per 1.73 m2 in the atorvastatin group and decreased 1.69±0.92 mL/min per 1.73 m2 in placebo group during a period of 60 months (P=0.016).
CONCLUSIONS
This post hoc analysis suggests that atorvastatin treatment may improve renal function in patients with prior stroke or transient ischemic attack with and without chronic kidney disease, and that atorvastatin treatment may prevent eGFR decline in patients with stroke and diabetes mellitus.
CLINICAL TRIAL REGISTRATION URL
http://www.clinicaltrials.gov. Unique identifier: NCT00147602.
背景与目的
较高的低密度脂蛋白胆固醇与慢性肾脏病进展更快相关；使用他汀类药物降低胆固醇，结合其多效性作用，如减轻炎症，可能具有肾脏保护作用。强化降低胆固醇水平预防卒中（SPARCL）试验评估了他汀类药物治疗对非心源性卒中或短暂性脑缺血发作、无已知冠心病且低密度脂蛋白胆固醇在2.6至4.9 mmol/L（100 - 190 mg/dL）之间的受试者发生非致命性和致命性卒中风险的影响。
方法
我们探讨了随机分配至阿托伐他汀80 mg/d或安慰剂对SPARCL研究受试者（n = 4731）估算肾小球滤过率（eGFR；使用肾脏病饮食改良研究方程的4变量公式）变化的影响，这些受试者总体上有（eGFR＜60 mL/min per 1.73 m2；n = 3119）和无（eGFR≥60 mL/min per 1.73 m2；n = 1600）慢性肾脏病，并根据基线血糖状态进行分析。
结果
治疗组间平均基线eGFR相似（阿托伐他汀组为65.5±0.26 mL/min per 1.73 m2，安慰剂组为65.6±0.26 mL/min per 1.73 m2；分别有33%和34%患有慢性肾脏病；P = 0.55）。60个月后，随机分配至阿托伐他汀组的受试者eGFR每1.73 m2增加3.46±0.33 mL/min，而随机分配至安慰剂组的受试者eGFR每1.73 m2增加1.42±0.34 mL/min（P＜0.001），与基线肾功能无关。在随机分组时患有糖尿病的亚组中，阿托伐他汀组的eGFR在60个月期间每1.73 m2增加1.12±0.92 mL/min，而安慰剂组每1.73 m2降低1.69±0.92 mL/min（P = 0.016）。
结论
这项事后分析表明，阿托伐他汀治疗可能改善既往有卒中或短暂性脑缺血发作且有或无慢性肾脏病患者的肾功能，并且阿托伐他汀治疗可能预防卒中合并糖尿病患者的eGFR下降。
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