医学
钙调神经磷酸酶
中止
优势比
内科学
西罗莫司
荟萃分析
置信区间
心脏移植
不利影响
依维莫司
PI3K/AKT/mTOR通路
肾功能
药理学
泌尿科
移植
细胞凋亡
化学
生物化学
作者
Douglas L. Jennings,Nicholas W. Lange,M. Shullo,F. Latif,Susan Restaino,V.K. Topkara,Koji Takeda,Hiroo Takayama,Yoshifumi Naka,Maryjane Farr,P.C. Colombo,William L. Baker
标识
DOI:10.1016/j.ijcard.2018.03.111
摘要
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.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).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 rates were similar (OR 0.91 [0.61 to 1.37], p = 0.62).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.
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