Cornu Catherine, Dufays Christophe, Gaillard Ségolène, Gueyffier François, Redonnet Michel, Sebbag Laurent, Roussoulières Ana, Gleissner Christian A, Groetzner Jan, Lehmkuhl Hans B, Potena Luciano, Gullestad Lars, Cantarovich Marcelo, Boissonnat Pascale
INSERM, CIC201, Lyon, France; CHU Lyon, Service de Pharmacologie Clinique, Lyon, France; Université de Lyon, UMR 5558, Lyon, France; Hospices Civils de Lyon, Hôpital Louis Pradel, Bron Cedex, France.
Br J Clin Pharmacol. 2014 Jul;78(1):24-32. doi: 10.1111/bcp.12289.
Calcineurin inhibitors (CNIs) taken after heart transplantation lead to excellent short-term outcomes, but long-term use may cause chronic nephrotoxicity. Our aim was to identify, appraise, select and analyse all high-quality research evidence relevant to the question of the clinical impact of CNI-sparing strategies in heart transplant patients.
We carried out a systematic review and meta-analysis of randomized controlled trials on CNI reduction in heart transplant recipients. Primary outcomes were kidney function and acute rejection after 1 year. Secondary outcomes included graft loss, all-cause mortality and adverse events.
Eight open-label studies were included, with 723 patients (four tested de novo CNI reduction and four maintenance CNI reduction). Calcineurin inhibitor reduction did not improve creatinine clearance at 12 months 5.46 [-1.17, 12.03] P = 0.32 I(2) = 65.4%. Acute rejection at 12 months (55/360 vs. 52/332), mortality (18/301 vs. 15/270) and adverse event rates (55/294 vs. 52/281) did not differ between the low-CNI and standard-CNI groups. There was significant benefit on creatinine clearance in patients with impaired renal function at 6 months [+12.23 (+5.26, +18.82) ml min(-1) , P = 0.0003] and at 12 months 4.63 [-4.55, 13.82] P = 0.32 I(2) = 75%.
This meta-analysis did not demonstrate a favourable effect of CNI reduction on kidney function, but there was no increase in acute rejection. To provide a better analysis of the influence of CNI reduction patterns and associated treatments, a meta-analysis of individual patient data should be performed.
心脏移植后使用钙调神经磷酸酶抑制剂（CNIs）可带来出色的短期疗效，但长期使用可能会导致慢性肾毒性。我们的目的是识别、评估、选择和分析所有与心脏移植患者中减少使用CNI策略的临床影响这一问题相关的高质量研究证据。
我们对心脏移植受者减少使用CNI的随机对照试验进行了系统评价和荟萃分析。主要结局为1年后的肾功能和急性排斥反应。次要结局包括移植物丢失、全因死亡率和不良事件。
纳入了8项开放标签研究，共723例患者（4项试验为初次使用时减少CNI，4项为维持期减少CNI）。减少使用钙调神经磷酸酶抑制剂在12个月时并未改善肌酐清除率[5.46（-1.17，12.03）]，P = 0.32，I² = 65.4%。低CNI组和标准CNI组在12个月时的急性排斥反应（55/360 vs. 52/332）、死亡率（18/301 vs. 15/270）和不良事件发生率（55/294 vs. 52/281）并无差异。肾功能受损的患者在6个月时肌酐清除率有显著改善[+12.23（+5.26，+18.82）ml·min⁻¹，P = 0.0003]，在12个月时为4.63（-4.55，13.82），P = 约0.32，I² = 75%。
这项荟萃分析未显示减少使用CNI对肾功能有有利影响，但急性排斥反应并未增加。为了更好地分析减少使用CNI模式及相关治疗的影响，应进行个体患者数据的荟萃分析。
