First united kingdom heart and renal protection (UK-HARP-1) study: Biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease
First united kingdom heart and renal protection (UK-HARP-1) study: Biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease
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DOI：
10.1053/j.ajkd.2004.11.015
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发表时间：
2005-03-01
影响因子：
13.2
通讯作者：
Wheeler, DC
中科院分区：
文献类型：
--
作者：
Baigent, C;Landray, M;Wheeler, DC
背景资料：慢性肾脏病患者心血管疾病的风险增加，但辛伐他汀和阿司匹林的疗效和安全性尚不清楚。研究方法：患者按2 × 2析因设计随机分配：（1）辛伐他汀每日20 mg与匹配安慰剂，（2）阿司匹林缓释片每日100 mg与匹配安慰剂。结果如下：总体而言，448例慢性肾脏疾病患者被随机分配（242例透析前肌酐水平>= 1.7 mg/dL [>= 150 μ mol/L]的患者，73例透析治疗患者和133例功能正常的移植患者）。12个月时研究治疗依从性为80%。每日100 mg阿司匹林治疗与大出血过多无关（阿司匹林，225例患者中的4例[2%]与安慰剂，223例患者中的6例[3%]; P=不显著[NS]），尽管轻微出血的发生率高出3倍（34/225 [15%] vs 12/223 [5%]; P= 0.001）。在那些基线时有透析前肾衰竭或功能正常的移植的患者中，阿司匹林并没有增加进展为透析治疗的患者数量（187例患者中7例[4%] vs 188例患者中6例[3%]; P = NS）或肌酐水平升高超过20%（63/187例患者[34%] vs 56/188例患者[30%]; P = NS）。在12个月的随访后，每日20毫克辛伐他汀可使非空腹总胆固醇水平降低18%（辛伐他汀，163 mg/dL [4.22 mmol/L] vs安慰剂，196 mg/dL [5.08 mmol/L]; P < 0.0001），直接测得的低密度脂蛋白胆固醇水平降低24%（89 mg/dL（2.31 mmol/L）对比114 mg/dL [2.96 mmol/L]; P < 0.0001），甘油三酯水平降低13%（166 mg/dL [1.87 mmol/L] vs 186 mg/dL [2.10 mmol/L]; P < 0.01），但对高密度脂蛋白胆固醇水平无显著影响（增加2%; P = NS）。接受辛伐他汀治疗与肝功能检查结果异常或肌酸激酶水平升高的风险无关。结论：在1年的治疗期间，辛伐他汀20 mg/d可使低密度脂蛋白胆固醇水平持续降低约四分之一，无毒性证据，阿司匹林100 mg/d基本上不会增加大出血发作的风险。现在需要更大规模的试验来评估这些治疗是否可以预防血管事件。
Background: Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group. Methods: Patients were randomly assigned in a 2 x 2 factorial design to the administration of: (1) 20 mg of simvastatin daily versus matching placebo, and (2) 100 mg of modified-release aspirin daily versus matching placebo. Results: Overall, 448 patients with chronic kidney disease were randomly assigned (242 predialysis patients with a creatinine level >= 1.7 mg/dL [>= 150 mu mol/L], 73 patients on dialysis therapy, and 133 patients with a functioning transplant). Compliance with study treatments was 80% at 12 months. Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds (aspirin, 4 of 225 patients [2%] versus placebo, 6 of 223 patients [3%]; P= not significant [NS]), although there was a 3-fold excess of minor bleeds (34 of 225 [15%] versus 12 of 223 patients [5%]; P= 0.001). Among those with predialysis renal failure or a functioning transplant at baseline, aspirin did not increase the number of patients who progressed to dialysis therapy (7 of 187 [4%] versus 6 of 188 patients [3%]; P = NS) or experienced a greater than 20% increase in creatinine level (63 of 187 patients [34%] versus 56 of 188 patients [30%]; P = NS). After 12 months of follow-up, allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18% (simvastatin, 163 mg/dL [4.22 mmol/L] versus placebo, 196 mg/dL [5.08 mmol/L]; P < 0.0001), directly measured low-density lipoprotein cholesterol levels by 24% (89 mg/dL (2.31 mmol/L] versus 114 mg/dL [2.96 mmol/L]; P < 0.0001), and triglyceride levels by 13% (166 mg/dL [1.87 mmol/L] versus 186 mg/dL [2.10 mmol/L]; P < 0.01), but there was no significant effect on high-density lipoprotein cholesterol levels (2% increase; P = NS). Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels. Conclusion: During a 1-year treatment period, simvastatin, 20 mg/d, produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels, with no evidence of toxicity, and aspirin, 100 mg/d, did not substantially increase the risk for a major bleeding episode. Much larger trials are now needed to assess whether these treatments can prevent vascular events.