Navaneethan Sankar D, Perkovic Vlado, Johnson David W, Nigwekar Sagar U, 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):CD005019. doi: 10.1002/14651858.CD005019.pub3.
Cardiovascular deaths account for the majority of deaths in kidney transplant recipients and dyslipidaemia contributes significantly to their cardiovascular disease. Statins are widely used in kidney transplant patients given their established benefits in the general population, however evidence favouring their use is lacking.
To assess the benefits and harms of statin therapy on mortality and renal outcomes in kidney transplant recipients.
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and hand searched reference lists of articles and scientific proceedings.
Randomised controlled trials (RCTs) and quasi-RCTs comparing statins with placebo, no treatment or other statins in kidney transplant recipients.
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model after testing for heterogeneity. Results were expressed as mean difference (MD) for continuous outcomes (lipid parameters) and risk ratio (RR) for dichotomous outcomes (mortality, allograft rejection, liver enzymes, occurrence of rhabdomyolysis and study withdrawal) with 95% confidence intervals (CI).
Sixteen studies (3229 patients) comparing statins versus placebo (15) or another statin (1) were included. Compared to placebo, statins did not decrease all-cause mortality (14 studies: RR 1.30, 95% CI 0.54 to 3.12). Point estimates favoured statins in terms of cardiovascular mortality (13 studies: RR 0.68, 95% CI 0.46 to 1.03) and non-fatal cardiovascular events (1 study: RR 0.70, 95% CI 0.48 to 1.01), however the results were not statistically significant. Compared to placebo, the use of statins was associated with a significantly lower end of treatment average total cholesterol (10 studies: MD -42.33 mg/dL (1.26 mmol/L), 95% CI -53.02 to -31.64), LDL cholesterol (10 studies: MD -46.15 mg/dL (1.19 mmol/L), 95% CI -55.97 to -36.33) and triglycerides (10 studies: MD -25.46 mg/dL (0.26 mmol/L), 95% CI -33.95 to 16.9). There was no significant difference in the risk of acute rejection (5 studies: RR 0.61; 95% C.I.0.32 to 1.16.) No data on chronic rejection was available and no major toxicity was noted.
AUTHORS' CONCLUSIONS: Statins significantly reduced hyperlipidaemia and tended to reduce cardiovascular events in kidney transplant recipients, but no effect has yet been demonstrated for mortality outcomes. Most of the data was derived from one large long-term study. Considering the significant impact of statins on all-cause and cardiovascular mortality in the general and predialysis populations, more studies are needed in kidney transplant patients.
心血管疾病死亡占肾移植受者死亡的大多数，血脂异常是导致其心血管疾病的重要因素。他汀类药物因其在普通人群中已证实的益处而被广泛应用于肾移植患者，但支持其使用的证据仍然不足。
评估他汀类药物治疗对肾移植受者死亡率和肾脏结局的益处和危害。
我们检索了MEDLINE、EMBASE、Cochrane对照试验中心注册库（CENTRAL），并手工检索了文章参考文献列表和科学会议记录。
比较他汀类药物与安慰剂、未治疗或其他他汀类药物在肾移植受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。在检验异质性后，使用随机效应模型进行统计分析。结果以连续变量（血脂参数）的平均差（MD）和二分变量（死亡率、移植肾排斥反应、肝酶、横纹肌溶解症的发生和研究退出）的风险比（RR）表示，并给出95%置信区间（CI）。
纳入了16项研究（3229例患者），比较了他汀类药物与安慰剂（15项）或另一种他汀类药物（1项）。与安慰剂相比，他汀类药物并未降低全因死亡率（14项研究：RR 1.30，95%CI 0.54至3.12）。在心血管死亡率（13项研究：RR 0.68，95%CI 0.46至1.03）和非致命性心血管事件方面（1项研究：RR 0.70，95%CI 0.48至1.01），点估计值倾向于他汀类药物，但结果无统计学意义。与安慰剂相比，使用他汀类药物与治疗结束时平均总胆固醇显著降低相关（10项研究：MD -42.33mg/dL（1.26mmol/L），95%CI -53.02至-31.64）、低密度脂蛋白胆固醇（10项研究：MD -46.15mg/dL（1.19mmol/L），95%CI -55.97至-36.33）和甘油三酯（10项研究：MD -25.46mg/dL（0.26mmol/L），95%CI -33.95至-16.9）。急性排斥反应风险无显著差异（5项研究：RR 0.61；95%CI 0.32至1.16）。没有关于慢性排斥反应的数据，也未观察到重大毒性。
他汀类药物可显著降低肾移植受者的高脂血症，并倾向于减少心血管事件，但尚未证明对死亡率有影响。大多数数据来自一项大型长期研究。鉴于他汀类药物对普通人群和透析前人群的全因死亡率和心血管死亡率有显著影响，肾移植患者需要更多的研究。
