Research progress of mTOR inhibitors in heart transplantation

doi:10.3877/cma.j.issn.1674-3903.2021.04.013

Abstract

Abstract:

Currently heart transplantation is the standard treatment for end-stage heart disease. Mammalian target of rapamycin (mTOR) inhibitors are increasingly used in heart transplantation recently. Numerous studies have demonstrated the efficacy of mTOR in attenuating cardiac allograft vasculopathy progression, improving renal function, and reducing cytomegalovirus infections and risks of malignancy. However, mTOR inhibitors have many adverse effects, such as hyperlipidemia, hyperglycemia, proteinuria, acute rejection, edema, risk of thrombotic events, and pulmonary toxicity. This review briefly discusses recent research progress of mTOR inhibitors in heart transplantation.

Key words: Heart transplantation, Mammalian target of rapamycin inhibitors, Immunosuppressive agents, Adverse effects

Yifan Zuo, Qi Wu, Zhiwei Wang. Research progress of mTOR inhibitors in heart transplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2021, 15(04): 250-256.

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References 65

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研究时间	目的	研究类型	免疫抑制方案	随访时间	主要结果
2018年^[7]	评价mTOR抑制剂在心脏移植儿童受者中伤口并发症的风险	回顾性	西罗莫司111例	90 d	1例在术后第17天出现切口起搏器感染、甲氧西林敏感金黄色葡萄球菌阳性。12例需要再次手术。西罗莫司在心脏移植儿童受者中伤口并发症的风险较低。
2018年^[8]	西罗莫司在预防心脏移植后CAV进展和长期预后的安全性和有效性	回顾性	西罗莫司268例，CNI 134例	8.9年	西罗莫司组和CNI组经血管内超声检查的斑块体积分别为(2.8±2.3)和(0.46±1.8)mm³、斑块指数(斑块体积/血管体积)分别为(12.2±9.6)%和(1.1±7.9)%，差异均有统计学意义(P均<0.0001)，且全因死亡率更低(HR＝0.47，95%CI：0.31~0.70)。
2019年^[11]	基于西罗莫司的免疫抑制方案能否降低心脏移植后恶性肿瘤的发病风险	RCT	西罗莫司307例，CNI 216例	10年	31%的CNI和13%的西罗莫司受者出现新发恶性肿瘤(调整后HR＝0.34，95%CI：0.18~0.62)。西罗莫司和CNI组转换前非黑素瘤皮肤癌发病风险类似(HR＝0.92，95%CI：0.66~1.28)；转换后西罗莫司组新发非黑素瘤皮肤癌(HR＝0.44，95%CI：0.28~0.69)和移植后淋巴增殖性疾病(HR＝0.13，95%CI：0.03~0.59)的风险降低。
2019年^[12]	比较mTOR抑制剂/无CNI方案和mTOR抑制剂/CNI减量方案的疗效	RCT	依维莫司/CNI减量74例，依维莫司/无CNI 71例	18个月	两种方案均有利于稳定肾功能，依维莫司/无CNI方案的肾脏益处至少与依维莫司/CNI减量方案相当，但会增加急性排斥反应的风险。
2021年^[13]	mTOR抑制剂相关蛋白尿对心脏移植后CAV的进展和长期预后的影响	回顾性	西罗莫斯137例	5.4年	转换为西罗莫司的受者蛋白尿(尿蛋白≥300 mg/24 h)发作更频繁(约26%)，合并蛋白尿的受者全因死亡率(HR＝3.8，95%CI：1.4~10.)和CAV事件风险(HR＝1.3，95%CI：0.46~3.8)更高。

研究时间	目的	研究类型	免疫抑制方案	随访时间	主要结果
2018年^[7]	评价mTOR抑制剂在心脏移植儿童受者中伤口并发症的风险	回顾性	西罗莫司111例	90 d	1例在术后第17天出现切口起搏器感染、甲氧西林敏感金黄色葡萄球菌阳性。12例需要再次手术。西罗莫司在心脏移植儿童受者中伤口并发症的风险较低。
2018年^[8]	西罗莫司在预防心脏移植后CAV进展和长期预后的安全性和有效性	回顾性	西罗莫司268例，CNI 134例	8.9年	西罗莫司组和CNI组经血管内超声检查的斑块体积分别为(2.8±2.3)和(0.46±1.8)mm³、斑块指数(斑块体积/血管体积)分别为(12.2±9.6)%和(1.1±7.9)%，差异均有统计学意义(P均<0.0001)，且全因死亡率更低(HR＝0.47，95%CI：0.31~0.70)。
2019年^[11]	基于西罗莫司的免疫抑制方案能否降低心脏移植后恶性肿瘤的发病风险	RCT	西罗莫司307例，CNI 216例	10年	31%的CNI和13%的西罗莫司受者出现新发恶性肿瘤(调整后HR＝0.34，95%CI：0.18~0.62)。西罗莫司和CNI组转换前非黑素瘤皮肤癌发病风险类似(HR＝0.92，95%CI：0.66~1.28)；转换后西罗莫司组新发非黑素瘤皮肤癌(HR＝0.44，95%CI：0.28~0.69)和移植后淋巴增殖性疾病(HR＝0.13，95%CI：0.03~0.59)的风险降低。
2019年^[12]	比较mTOR抑制剂/无CNI方案和mTOR抑制剂/CNI减量方案的疗效	RCT	依维莫司/CNI减量74例，依维莫司/无CNI 71例	18个月	两种方案均有利于稳定肾功能，依维莫司/无CNI方案的肾脏益处至少与依维莫司/CNI减量方案相当，但会增加急性排斥反应的风险。
2021年^[13]	mTOR抑制剂相关蛋白尿对心脏移植后CAV的进展和长期预后的影响	回顾性	西罗莫斯137例	5.4年	转换为西罗莫司的受者蛋白尿(尿蛋白≥300 mg/24 h)发作更频繁(约26%)，合并蛋白尿的受者全因死亡率(HR＝3.8，95%CI：1.4~10.)和CAV事件风险(HR＝1.3，95%CI：0.46~3.8)更高。

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