Landray Martin, Baigent Colin, Leaper Craig, Adu Dwomoa, Altmann Paul, Armitage Jane, Ball Simon, Baxter Alex, Blackwell Lisa, Cairns Hugh S, Carr Sue, Collins Rory, Kourellias Karen, Rogerson Mary, Scoble John E, Tomson Charles R V, Warwick Graham, Wheeler David C
Clinical Trial Service Unit, University of Oxford, Churchill Hospital, Oxford, UK.
Am J Kidney Dis. 2006 Mar;47(3):385-95. doi: 10.1053/j.ajkd.2005.11.018.
Evaluating the effects of decreasing low-density lipoprotein (LDL) cholesterol levels requires large randomized trials. In preparation for such a trial, we assessed the biochemical efficacy, safety, and tolerability of adding ezetimibe, 10 mg/d, to simvastatin, 20 mg/d, as initial therapy for such patients.
Two hundred three patients (152 predialysis patients with creatinine levels > or = 1.7 mg/dL [> or = 150 micromol/L], 18 patients on peritoneal dialysis therapy, and 33 patients on hemodialysis therapy) were randomly assigned to the administration of simvastatin, 20 mg/d, plus ezetimibe, 10 mg/d; or simvastatin, 20 mg, plus placebo ezetimibe daily.
After 6 months, allocation to simvastatin monotherapy was associated with a 31-mg/dL (0.8-mmol/L) decrease in nonfasting LDL cholesterol levels compared with baseline. Allocation to simvastatin plus ezetimibe produced an additional 18-mg/dL (0.47-mmol/L) decrease in LDL cholesterol level, representing an incremental 21% reduction over that achieved with simvastatin monotherapy (P < 0.0001). There were no statistically significant effects of the addition of ezetimibe to simvastatin on triglyceride or high-density lipoprotein cholesterol levels. Ezetimibe was not associated with an excess risk of abnormal liver function test results or of elevated creatine kinase levels and did not impair absorption of fat-soluble vitamins. There were no serious adverse events caused by study treatment.
This 6-month study shows that the addition of ezetimibe to simvastatin, 20 mg/d, as initial therapy for patients with chronic kidney disease was well tolerated and produced an additional 21% decrease in LDL cholesterol levels. The clinical efficacy and safety of combination therapy in this population are now being assessed in a large randomized trial.
评估降低低密度脂蛋白（LDL）胆固醇水平的效果需要进行大型随机试验。在筹备此类试验时，我们评估了对于此类患者，初始治疗每日添加10毫克依折麦布至20毫克辛伐他汀的生化疗效、安全性和耐受性。
203例患者（152例肌酐水平≥1.7毫克/分升[≥150微摩尔/升]的透析前患者、18例接受腹膜透析治疗的患者和33例接受血液透析治疗的患者）被随机分配接受每日20毫克辛伐他汀加10毫克依折麦布治疗；或每日20毫克辛伐他汀加安慰剂依折麦布治疗。
6个月后，与基线相比，单独使用辛伐他汀治疗使非空腹LDL胆固醇水平降低了31毫克/分升（0.8毫摩尔/升）。辛伐他汀加依折麦布治疗使LDL胆固醇水平额外降低了18毫克/分升（0.47毫摩尔/升），比单独使用辛伐他汀治疗实现的降低幅度增加了21%（P<0.0001）。辛伐他汀加依折麦布对甘油三酯或高密度脂蛋白胆固醇水平没有统计学上的显著影响。依折麦布与肝功能检查结果异常或肌酸激酶水平升高的额外风险无关，也不影响脂溶性维生素的吸收。研究治疗未导致严重不良事件。
这项为期6个月的研究表明，对于慢性肾病患者，初始治疗每日添加10毫克依折麦布至20毫克辛伐他汀耐受性良好，LDL胆固醇水平额外降低了21%。目前正在一项大型随机试验中评估该联合治疗在此类人群中的临床疗效和安全性。
