Outcomes associated with mammalian target of rapamycin (mTOR) inhibitors in heart transplant recipients: A meta-analysis
Outcomes associated with mammalian target of rapamycin (mTOR) inhibitors in heart transplant recipients: A meta-analysis
复制标题
DOI：
10.1016/j.ijcard.2018.03.111
复制
发表时间：
2018-08-15
影响因子：
3.5
通讯作者：
Baker, William L.
中科院分区：
文献类型：
--
作者：
Jennings, Douglas L.;Lange, Nicholas;Baker, William L.
背景：评估 mTOR 抑制剂使用心脏移植 (HT) 患者的数据来自相对较小的研究，并且关于其具体作用存在争议。我们对随机试验进行了荟萃分析，以评估 mTOR 抑制剂在 HT 患者中的疗效和安全性。方法：我们对 Medline 和 Embase 进行了截至 2017 年 7 月的系统文献检索，确定了评估 mTOR 抑制剂在 HT 患者中的研究，报告了对冠状动脉同种异体移植血管病变 (CAV)、肾功能、急性细胞排斥 (ACR)、巨细胞病毒 (CMV) 感染和因药物不良事件 (ADE) 导致的停药的影响。使用随机效应模型汇集数据，产生平均差（MD；对于连续数据）或比值比（OR；对于二分数据）和 95% 置信区间 (CI)。 结果：14 项试验报告了至少一项感兴趣的结果。与钙调神经磷酸酶抑制剂/吗替麦考酚酯 (CNI/MMF) 相比，mTOR 平均最大内膜厚度的变化显着降低（-0.04 [-0.07 至 -0.02]）。与 CNI/MMF 治疗相比，mTOR 方案的 CMV 感染率也显着降低（0.26；[0.2 至 0.32]）。保留 CNI 的方案中 ACR 更频繁（6.46 [1.55 至 26.95]）。 CNI 保留疗法的 eGFR 显着改善（平均差 12.09 mL/min [2.43 至 21.74]），但 CNI/mTOR 与 CNI/MMF 方案之间的 eGFR 相似（p > 0.05）。含 mTOR 的方案因 ADE 导致的停药率较高（OR 2.15 [1.28 至 3.60]，p= 0.01），而死亡率相似（OR 0.91 [0.61 至 1.37]，p= 0.62）。结论：含 mTOR 的方案可以降低 HT 接受者的 CAV 和 CMV 风险。 mTOR/MMF 组合可保留肾功能，但会增加 ACR 的风险。 (C) 2018 Elsevier B.V. 保留所有权利。
Background: Data evaluating mTOR inhibitor use heart transplant (HT) patients comes from relatively small studies and controversy exists regarding their specific role. We performed a meta-analysis of randomized trials to evaluate the efficacy and safety of mTOR inhibitors in HT patients.Methods: We performed a systematic literature search of Medline and Embase through July 2017 identifying studies evaluating mTOR inhibitors in HT patients reporting effects on coronary allograft vasculopathy (CAV), renal function, acute cellular rejection (ACR), cytomegalovirus (CMV) infection, and discontinuation due to adverse drug events (ADE). Data were pooled using a random-effects model producing a mean difference (MD; for continuous data) or odds ratio (OR; for dichotomous data) and 95% confidence interval (CI).Results: 14 trials reported at least one outcome of interest. Change in mean maximal intimal thickness was significantly reduced with mTOR (-0.04 [-0.07 to -0.02]) compared to calcineurin inhibitor/mycophenolate mofetil (CNI/MMF). Rates of CMV infection were also significantly reduced (0.26; [0.2 to 0.32]) with mTOR regimens compared to CNI/MMF therapy. ACR was more frequent with CNI-sparing regimens 6.46 [1.55 to 26.95]). eGFR was significantly improved with CNI-sparing therapies (mean difference 12.09 mL/min [2.43 to 21.74]), but was similar between CNI/mTOR versus CNI/MMF regimens (p > 0.05). Rates of discontinuation due to ADE were higher in mTOR-containing regimens (OR 2.15 [1.28 to 3.60], p= 0.01), while mortality rateswere similar (OR 0.91 [0.61 to 1.37], p= 0.62).Conclusions: mTOR-containing regimens can attenuate CAV and CMV risk in HT recipients. A mTOR/MMF combination preserves renal function but increases the risk of ACR. (C) 2018 Elsevier B.V. All rights reserved.