Previous studies have reported superiority of mechanistic target-of-rapamycin (mTOR) antagonists (mTA) over calcineurin inhibitors (CNI) as part of maintenance immunosuppression (IS) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). MEDLINE and EMBASE were searched through October 2019 for studies comparing maintenance IS with mTA + antimetabolites (AM), CNI + mTA or CNI + AM post HT. The main outcomes were all-cause mortality, CAV, acute rejection, CMV infections, and change in eGFR. To compare different IS antagonists, a random-effects network meta-analysis was performed. We used p-scores to rank best treatments per outcome. Our search identified fifteen eligible studies (5 studies comparing mTA + AM vs. CNI + AM, 9 comparing CNI + mTA vs. CNI + AM, 1 comparing mTA + AM vs. CNI + mTA, 8 using everolimus and 7 sirolimus as mTA) reporting the selected outcomes. We did not identify any statistical difference in all-cause mortality among the three IS regimens without heterogeneity among studies. CAV rates were significantly lower with CNI + mTA (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.3-0.92). Acute rejection rates were significantly lower with CNI + AM (OR 0.26, 95% CI 0.12-0.56) and with CNI + mTA (OR 0.16, 95% CI 0.07-0.33) compared with mTA + AM without significant heterogeneity (I2 = 43%, p = 0.9). CMV infections were significantly lower with mTA + AM (OR 0.13, 95% CI 0.03-0.46) and with CNI + mTA (OR 0.27, 95% CI 0.2-0.38) compared with CNI + AM without heterogeneity. mTA + AM led to higher eGFR compared with CNI + AM (9.06 ml/min/1.73 m2, 95% CI 3.15-14.97) and CNI + Mta (9.64 ml/min/1.73 m2, 95% CI 0.91-18.36), but the heterogeneity among studies was significant. CNI + mTA ranked better for CAV (p = 0.78), and acute rejection (p = 0.99) while mTA + AM for CMV infection (p = 0.94) and improvement in renal function (p = 0.93) than other regimens. Different IS regimens have similar effects on survival post HT, but CNI + mTA was associated with lower CAV rates, and acute rejection, while mTA + AM with less CMV infection post HT.

中文翻译：

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心脏移植中的维持免疫抑制：来自各种免疫抑制方案的网络荟萃分析的见解。

以前的研究报告了雷帕霉素 (mTOR) 拮抗剂 (mTA) 的机制优于钙调神经磷酸酶抑制剂 (CNI) 作为维持免疫抑制 (IS) 的一部分，以减轻心脏移植 (HT) 后心脏同种异体移植血管病变 (CAV)。截至 2019 年 10 月，在 MEDLINE 和 EMBASE 中搜索了将维持 IS 与 mTA + 抗代谢物 (AM)、CNI + mTA 或 CNI + AM 后 HT 进行比较的研究。主要结果是全因死亡率、CAV、急性排斥反应、CMV 感染和 eGFR 的变化。为了比较不同的 IS 拮抗剂，进行了随机效应网络荟萃分析。我们使用 p 分数对每个结果的最佳治疗进行排名。我们的搜索确定了 15 项符合条件的研究（5 项比较 mTA + AM 与 CNI + AM 的研究，9 项比较 CNI + mTA 与 CNI + AM 的研究，1 项比较 mTA + AM 与 CNI + mTA 的研究，8 使用依维莫司和 7 西罗莫司作为 mTA）报告选定的结果。我们没有发现三种 IS 方案在全因死亡率方面有任何统计学差异，研究之间没有异质性。CNI + mTA 的 CAV 率显着降低（比值比 [OR] 0.53，95% 置信区间 [CI] 0.3-0.92）。与无显着异质性的 mTA + AM 相比，CNI + AM（OR 0.26，95% CI 0.12-0.56）和 CNI + mTA（OR 0.16，95% CI 0.07-0.33）的急性排斥率显着降低（I2 = 43%） , p = 0.9)。与无异质性的 CNI + AM 相比，mTA + AM（OR 0.13，95% CI 0.03-0.46）和 CNI + mTA（OR 0.27，95% CI 0.2-0.38）的 CMV 感染显着降低。与 CNI + AM（9.06 ml/min/1.73 m2，95% CI 3.15-14.97）和 CNI + Mta（9.64 ml/min/1.73 m2，95% CI 0.91-18.36）相比，mTA + AM 导致更高的 eGFR，但研究之间的异质性很大。CNI + mTA 对 CAV (p = 0.78) 和急性排斥反应 (p = 0.99) 的排名更好，而 mTA + AM 对 CMV 感染 (p = 0.94) 和肾功能改善 (p = 0.93) 的排名优于其他方案。不同的 IS 方案对 HT 后的生存有相似的影响，但 CNI + mTA 与较低的 CAV 率和急性排斥反应相关，而 mTA + AM 与较少的 HT 后 CMV 感染有关。