Navaneethan Sankar D, Pansini Francesca, Perkovic Vlado, Manno Carlo, Pellegrini Fabio, Johnson David W, Craig Jonathan C, Strippoli Giovanni F M
Department of Nephrology and Hypertension, Glickman Urological and Kidney institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Cochrane Database Syst Rev. 2009 Apr 15(2):CD007784. doi: 10.1002/14651858.CD007784.
Dyslipidaemia occurs frequently in chronic kidney disease (CKD) patients and contributes both to cardiovascular disease and worsening renal function. Statins are widely used in non-dialysis dependent CKD patients (pre-dialysis) even though evidence favouring their use is lacking.
To evaluate the benefits and harms of statins in CKD patients who were not receiving renal replacement therapy.
We searched MEDLINE, EMBASE, CENTRAL (in The Cochrane Library), and hand-searched reference lists of textbooks, articles and scientific proceedings.
Randomised controlled trials (RCTs) and quasi-RCTs comparing statins with placebo, no treatment or other statins in adult pre-dialysis CKD patients.
Two authors independently assessed study quality and extracted data. Results were expressed as mean difference (MD) for continuous outcomes (lipids, creatinine clearance and proteinuria) and risk ratio (RR) for dichotomous outcomes (all-cause mortality, cardiovascular mortality, fatal and non-fatal cardiovascular events, elevated liver enzymes, rhabdomyolysis and withdrawal rates) with 95% confidence intervals (CI).
Twenty six studies (25,017 participants) comparing statins with placebo were identified. Total cholesterol decreased significantly with statins (18 studies, 1677 patients: MD -41.48 mg/dL, 95% CI -49.97 to -33.99). Similarly, LDL cholesterol decreased significantly with statins (16 studies, 1605 patients: MD -42.38 mg/dL, 95% CI -50.71 to -34.05). Statins decreased both the risk of all-cause (21 RCTs, 18,781 patients, RR 0.81, 95% CI 0.74, 0.89) and cardiovascular deaths (20 studies, 18,746 patients: RR 0.80, 95% CI 0.70 to 0.90). Statins decreased 24-hour urinary protein excretion (6 studies, 311 patients: MD -0.73 g/24 h, 95% CI -0.95 to -0.52), but there was no significant improvement in creatinine clearance - a surrogate marker of renal function (11 studies, 548 patients: MD 1.48 mL/min, 95% CI -2.32 to 5.28).The incidence of rhabdomyolysis, elevated liver enzymes and withdrawal rates due to adverse events (well known complications of statins use), were not significantly different between patients receiving statins and placebo.
AUTHORS' CONCLUSIONS: Statins significantly reduced the risk of all-cause and cardiovascular mortality in CKD patients who are not receiving renal replacement therapy. They do not impact on the decline in renal function as measured by creatinine clearance, but may reduce protein excretion in urine. Statins appear to be safe in this population. Guidelines recommendations on hyperlipidaemia management in CKD patients could therefore be followed targeting higher proportions of patients receiving a statin, with appropriate monitoring of adverse events.
血脂异常在慢性肾脏病(CKD)患者中频繁出现,会导致心血管疾病和肾功能恶化。他汀类药物广泛应用于非透析依赖的CKD患者(透析前),尽管支持其使用的证据不足。
评估他汀类药物在未接受肾脏替代治疗的CKD患者中的益处和危害。
我们检索了MEDLINE、EMBASE、CENTRAL(考克兰系统评价数据库),并手工检索了教科书、文章和科学会议论文集的参考文献列表。
比较他汀类药物与安慰剂、不治疗或其他他汀类药物在成年透析前CKD患者中的随机对照试验(RCT)和半随机对照试验。
两位作者独立评估研究质量并提取数据。结果以连续变量结果(血脂、肌酐清除率和蛋白尿)的平均差(MD)以及二分类变量结果(全因死亡率、心血管死亡率、致命和非致命心血管事件、肝酶升高、横纹肌溶解和撤药率)的风险比(RR)表示,并给出95%置信区间(CI)。
共纳入26项比较他汀类药物与安慰剂的研究(25,017名参与者)。他汀类药物使总胆固醇显著降低(18项研究,1677名患者:MD -41.48mg/dL,95%CI -49.97至-33.99)。同样,他汀类药物使低密度脂蛋白胆固醇显著降低(16项研究,1605名患者:MD -42.38mg/dL,95%CI -50.71至-34.05)。他汀类药物降低了全因死亡风险(21项RCT,18,781名患者,RR 0.81,95%CI 0.74至0.89)和心血管死亡风险(20项研究,18,746名患者:RR 0.80,95%CI 0.70至0.90)。他汀类药物降低了24小时尿蛋白排泄量(6项研究,311名患者:MD -0.73g/24h,95%CI -0.95至-0.52),但肌酐清除率(肾功能的替代指标)没有显著改善(11项研究,548名患者:MD 1.48mL/min,95%CI -2.32至5.28)。接受他汀类药物治疗的患者与接受安慰剂治疗的患者相比,横纹肌溶解、肝酶升高的发生率以及因不良事件导致的撤药率没有显著差异。
他汀类药物显著降低了未接受肾脏替代治疗的CKD患者的全因死亡和心血管死亡风险。它们对以肌酐清除率衡量的肾功能下降没有影响,但可能减少尿蛋白排泄。他汀类药物在该人群中似乎是安全的。因此,CKD患者高脂血症管理的指南建议可以针对更高比例接受他汀类药物治疗的患者,并对不良事件进行适当监测来遵循。