BACKGROUND Early substitution of calcineurin inhibitor (CNI) with mammalian target of rapamycin inhibitors has been shown to improve kidney function and reduce intimal hyperplasia in heart transplant (HTx) recipients but data on long-term outcome of such a regime are still sparse. METHODS In the SCHEDULE trial, 115 de novo HTx recipients were randomized to (1) everolimus with reduced exposure of CNI followed by CNI withdrawal at week 7-11 post-transplant or (2) standard-exposure with CNI. Both groups received mycophenolate mofetil and corticosteroids. Herein we report on the 10-12-year long-term follow-up of the study. RESULTS A total of 78 patients attended the follow-up visit at a median time of 11 years post-transplant. In the everolimus intention to treat (ITT) group 87.5% (35/40 patients) still received everolimus and in the CNI ITT group 86.8% (33/38) still received CNI. Estimated glomerular filtration rate (eGFR) (least square mean (95% CI)) at the 10-12 years visit was 82.7 (74.2-91.1) ml/min/1.73 m2 and 61.0 (52.3-69.7) ml/min/1.73 m2 in the everolimus and CNI group, respectively (p < 0.001). Graft function measured by ejection fraction, ECG, NT-proBNP and drug safety were comparable between groups. During the study period there was a total of 28 deaths, but there was no difference in survival between the everolimus and the CNI group (aHR 0.61 (95% CI 0.29-1.30) p = 0.20). For the composite endpoint of death, re-transplantation, myocardial infarction, PCI, dialysis, kidney transplantation or cancer no between group differences were found (aHR 1.0 (95% CI 0.57-1.77) p = 0.99). CONCLUSIONS De novo HTx patients randomized to everolimus and low dose CNI followed by CNI free therapy sustained significantly better long-term kidney function than patients randomized to standard therapy. The graft function at 10-12 years was similar in both groups and there was no difference in survival.

中文翻译：

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随机、前瞻性斯堪的纳维亚心脏移植依维莫司从头研究的长期随访，包括早期避免钙调磷酸酶抑制剂 （SCHEDULE） 试验。


背景 用哺乳动物靶标雷帕霉素抑制剂 （CNI） 早期替代钙调神经磷酸酶抑制剂 （CNI） 已被证明可以改善心脏移植 （HTx） 受者的肾功能并减少内膜增生，但关于这种方案的长期结果的数据仍然很少。方法 在 SCHEDULE 试验中，115 名新发 HTx 受者被随机分配到 （1） 减少 CNI 暴露的依维莫司，然后在移植后第 7-11 周退出 CNI 或 （2） 标准暴露 CNI。两组均接受吗替麦考酚酯和皮质类固醇治疗。在此，我们报告了该研究的 10-12 年长期随访。结果 共有 78 例患者在移植后中位时间为 11 年参加了随访。在依维莫司意向治疗 （ITT） 组中，87.5% （35/40 名患者） 仍接受依维莫司治疗，在 CNI ITT 组中，86.8% （33/38） 仍接受 CNI。依维莫司组和 CNI 组在 10-12 年访视时的估计肾小球滤过率 （eGFR） （最小二乘均值 （95% CI）） 分别为 82.7 （74.2-91.1） ml/min/1.73 m2 和 61.0 （52.3-69.7） ml/min/1.73 m2 （p < 0.001）。通过射血分数、 ECG 、 NT-proBNP 和药物安全性测量的移植物功能在组间具有可比性。在研究期间，共有 28 例死亡，但依维莫司组和 CNI 组之间的生存率没有差异 （aHR 0.61 （95% CI 0.29-1.30） p = 0.20）。对于死亡、再移植、心肌梗死、PCI、透析、肾移植或癌症的复合终点，未发现组间差异（aHR 1.0 （95% CI 0.57-1.77） p = 0.99）。 结论 随机接受依维莫司和低剂量 CNI 后无 CNI 治疗的新发 HTx 患者比随机接受标准治疗的患者长期肾功能明显更好。两组 10-12 岁的移植物功能相似，生存率无差异。