Maintenance immunosuppression in heart transplantation: insights from network meta-analysis of various immunosuppression regimens
Maintenance immunosuppression in heart transplantation: insights from network meta-analysis of various immunosuppression regimens
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心脏移植中的维持性免疫抑制：各种免疫抑制方案的网络荟萃分析的见解
作者：
H. Ueyama;T. Kuno;H. Takagi;P. Alvarez;R. Asleh;A. Briasoulis
先前的研究已经报道了作为维持免疫抑制（IS）的一部分，雷帕霉素（mTOR）拮抗剂（mTA）在减轻心脏移植（HT）后心脏移植物血管病变（CAV）方面优于钙调磷酸酶抑制剂（CNI）。检索了截至2019年10月的MEDLINE和EMBASE，以比较维持IS与mTA+抗代谢药（AM）、CNI + mTA或HT后CNI + AM的研究。主要结局为全因死亡率、CAV、急性排斥反应、CMV感染和eGFR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评分来根据结局对最佳治疗进行排名。我们的检索确定了15项报告选定结局的合格研究（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项使用依维莫司，7项西罗莫司作为mTA）。我们没有发现三种IS方案之间的全因死亡率有任何统计学差异，研究之间没有异质性。CNI + mTA组的CAV发生率显著较低（比值比[OR] 0.53，95%置信区间[CI] 0.3 - 0.92）。与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）的急性排斥反应率显著降低，无显著异质性（I 2 = 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感染显著降低。mTA + AM导致eGFR高于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），但研究间异质性显著。CNI + mTA在CAV（p = 0.78）和急性排斥反应（p = 0.99）方面排名更好，而mTA + AM在CMV感染（p = 0.94）和肾功能改善（p = 0.93）方面排名更好。不同IS方案对HT后生存率的影响相似，但CNI + mTA与较低的CAV发生率和急性排斥反应相关，而mTA + AM与HT后较少的CMV感染相关。
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 (I 2 = 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.