Haynes Richard, Lewis David, Emberson Jonathan, Reith Christina, Agodoa Lawrence, Cass Alan, Craig Jonathan C, de Zeeuw Dick, Feldt-Rasmussen Bo, Fellström Bengt, Levin Adeera, Wheeler David C, Walker Rob, Herrington William G, Baigent Colin, Landray Martin J
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
J Am Soc Nephrol. 2014 Aug;25(8):1825-33. doi: 10.1681/ASN.2013090965. Epub 2014 May 1.
Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared with placebo. There was a nonsignificant 3% reduction in the incidence of ESRD (1057 [33.9%] cases with simvastatin plus ezetimibe versus 1084 [34.6%] cases with placebo; rate ratio, 0.97; 95% confidence interval [95% CI], 0.89 to 1.05; P=0.41). Similarly, allocation to simvastatin plus ezetimibe had no significant effect on the prespecified tertiary outcomes of ESRD or death (1477 [47.4%] events with treatment versus 1513 [48.3%] events with placebo; rate ratio, 0.97; 95% CI, 0.90 to 1.04; P=0.34) or ESRD or doubling of baseline creatinine (1189 [38.2%] events with treatment versus 1257 [40.2%] events with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD.
降低低密度脂蛋白胆固醇可降低慢性肾脏病（CKD）患者发生动脉粥样硬化事件的风险，但这种治疗对肾脏疾病进展的影响仍不确定。在此项研究中，6245例未接受透析治疗的CKD患者被随机分为两组，分别每日服用辛伐他汀（20毫克）加依折麦布（10毫克）或匹配的安慰剂。主要预先设定的肾脏结局为终末期肾病（ESRD，定义为开始维持性透析或肾移植）。在4.8年的随访期间，与安慰剂相比，分配至辛伐他汀加依折麦布组导致低密度脂蛋白胆固醇平均差异（标准误）为0.96（0.02）毫摩尔/升。ESRD发生率有3%的降低，但无统计学意义（辛伐他汀加依折麦布组1057例[33.9%]，安慰剂组1084例[34.6%]；率比为0.97；95%置信区间[95%CI]为0.89至1.05；P = 0.41）。同样，分配至辛伐他汀加依折麦布组对预先设定的ESRD或死亡的三级结局（治疗组1477例[47.4%]事件，安慰剂组1513例[48.3%]事件；率比为0.97；95%CI为0.90至1.04；P = 0.34）或ESRD或基线肌酐翻倍（治疗组1189例[38.2%]事件，安慰剂组1257例[40.2%]事件；率比为0.93；95%CI为0.86至1.01；P = 0.09）均无显著影响。探索性分析也显示对估算肾小球滤过率（eGFR）的变化率无显著影响。在广泛的CKD患者中，将低密度脂蛋白胆固醇降低1毫摩尔/升在5年内并未减缓肾脏疾病进展。
