Cyclosporin versus tacrolimus for liver transplanted patients.
Cyclosporin versus tacrolimus for liver transplanted patients.
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DOI：
10.1002/14651858.cd005161.pub2
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发表时间：
2006-10
期刊：
影响因子：
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通讯作者：
E. Haddad;Vivian Charles McAlister;E. Renouf;R. Malthaner;M. Kjaer;L. Gluud
中科院分区：
文献类型：
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作者：
E. Haddad;Vivian Charles McAlister;E. Renouf;R. Malthaner;M. Kjaer;L. Gluud
背景技术大多数肝移植受者接受环孢素或他克莫司以预防排斥反应。这两种药物均抑制钙调神经磷酸酶，这被认为是其抗排斥作用和主要毒性的机制。这些药物具有不同的药代动力学特征和效力。几项随机临床试验在肝移植受者中比较了环孢素和他克莫司，但尚不清楚哪种更优越。目的 评估环孢素与他克莫司免疫抑制对肝移植患者的有益和有害影响。检索策略 检索 Cochrane 肝胆组对照试验注册库、Cochrane 图书馆的 Cochrane 对照试验中央注册库、MEDLINE、EMBASE 和 Science Citation Index Expanded 以及会议记录（2005 年 8 月），以识别相关的随机临床试验。我们的搜索包括扫描相关文章中的参考文献列表以及与研究人员和制药公司的通信。选择标准 所有将他克莫司与环孢菌素用于首次肝移植受者初始治疗进行比较的随机临床试验。我们纳入了随机试验，不考虑盲法、语言和发表状态。数据收集和分析 主要结果指标是全因死亡率。数据被合成（固定效应模型），结果表示为相对风险 (RR)，小于 1.0 的值有利于他克莫司，置信区间 (CI) 为 95%。两位作者独立评估试验的资格、质量并提取数据。主要结果 我们纳入了 16 项随机试验。他克莫司组的死亡人数为 254 例（1899 例患者），环孢素组的死亡人数为 302 例（1914 例患者）。一年时，接受他克莫司治疗的受者的死亡率（RR 0.85，95% CI 0.73 - 0.99）和移植物丢失（RR 0.73，95% CI 0.61 - 0.86）显着降低。他克莫司减少了第一年出现急性排斥反应（RR 0.81，95% CI 0.75 - 0.88）和类固醇抵抗排斥反应（RR 0.54，95% CI 0.47 - 0.74）的受者数量。在淋巴增殖性疾病或重新透析率方面没有发现差异，但他克莫司组发生更多的重新需要胰岛素的糖尿病（RR 1.38，95% CI 1.01至1.86）。退出环孢素治疗的患者多于退出他克莫司的患者（RR 0.57，95% CI 0.49 至 0.66）。作者的结论 他克莫司在提高生存率（患者和移植物）和预防肝移植后急性排斥反应方面优于环孢菌素，但它增加了移植后糖尿病的风险。用他克莫司代替环孢素治疗 100 名受者，可分别避免 9 名和 7 名患者的急性排斥反应和类固醇耐药性排斥反应，以及分别避免 5 名和 2 名患者的移植物丢失和死亡，但另外 4 名患者会在肝移植后出现糖尿病。
BACKGROUND Most liver transplant recipients receive either cyclosporin or tacrolimus to prevent rejection. Both drugs inhibit calcineurin phosphatase which is thought to be the mechanism of their anti-rejection effect and principle toxicities. The drugs have different pharmacokinetic profiles and potencies. Several randomised clinical trials have compared cyclosporin and tacrolimus in liver transplant recipients, but it remains unclear which is superior. OBJECTIVES To evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. SEARCH STRATEGY The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded, and conference proceedings were searched (August 2005) to identify relevant randomised clinical trials. Our search included scanning of reference lists in relevant articles and correspondence with investigators and pharmaceutical companies. SELECTION CRITERIA All randomised clinical trials where tacrolimus was compared with cyclosporin for the initial treatment of first-time liver transplant recipients. We included randomised trials irrespective of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS The primary outcome measure was all-cause mortality. Data were synthesised (fixed-effect model) and results expressed as relative risk (RR), values less than 1.0 favouring tacrolimus, with 95% confidence intervals (CI). Two authors assessed trials for eligibility, quality, and extracted data independently. MAIN RESULTS We included 16 randomised trials. The number of deaths was 254 in the tacrolimus group (1899 patients) and 302 in the cyclosporin group (1914 patients). At one year, mortality (RR 0.85, 95% CI 0.73 to 0.99) and graft loss (RR 0.73, 95% CI 0.61 to 0.86) were significantly reduced in tacrolimus-treated recipients. Tacrolimus reduced the number of recipients with acute rejection (RR 0.81, 95% CI 0.75 to 0.88), and steroid-resistant rejection (RR 0.54, 95% CI 0.47 to 0.74) in the first year. Differences were not seen with respect to lymphoproliferative disorder or de-novo dialysis rates, but more de-novo insulin-requiring diabetes mellitus (RR 1.38, 95% CI 1.01 to 1.86) occurred in the tacrolimus group. More patients were withdrawn from cyclosporin therapy than from tacrolimus (RR 0.57, 95% CI 0.49 to 0.66). AUTHORS' CONCLUSIONS Tacrolimus is superior to cyclosporin in improving survival (patient and graft) and preventing acute rejection after liver transplantation, but it increases the risk of post-transplant diabetes. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid acute rejection and steroid-resistant rejection in nine and seven patients, respectively, and graft loss and death in five and two patients, respectively, but four additional patients would develop diabetes after liver transplantation.