Abstract：
OBJECTIVE: The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs, potentially increasing adverse events. Safe use of drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data.
METHODS: We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child-Turcotte-Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety.
RESULTS: Fifty four studies were included. All DOACs were classified as \'no additional risks known\' for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as \'no additional risks known\'. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as \'unsafe\' in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as \'unknown\' for CTP C.
CONCLUSIONS: DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.
METHODS: We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child-Turcotte-Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety.
RESULTS: Fifty four studies were included. All DOACs were classified as \'no additional risks known\' for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as \'no additional risks known\'. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as \'unsafe\' in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as \'unknown\' for CTP C.
CONCLUSIONS: DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.
摘要：
目的：直接口服抗凝药（DOACs）在肝硬化患者中越来越受欢迎。肝硬化对药物的药代动力学有主要影响，潜在增加的不良事件。在肝硬化中安全使用药物需要勤奋的风险效益分析。本研究的目的是根据药代动力学的系统评价，制定肝硬化中安全使用DOAC的实践建议，药效学和安全性数据。
方法：我们进行了系统的文献检索，以确定有关药代动力学的研究，肝硬化DOAC的药效学和安全性。使用Child-Turcotte-Pugh（CTP）分类，根据肝硬化的严重程度收集数据并在汇总表中显示。一个多学科专家小组评估了结果，并根据安全性对DOAC进行了分类。
结果：纳入54项研究。所有DOAC被归类为“CTPA没有已知的额外风险”。对于CTPB，阿哌沙班,dabigatran和edoxaban被归类为“没有已知的额外风险”。阿哌沙班和依度沙班显示肝硬化患者的不良事件较少，而达比加群可能受到肝硬化严重程度的影响较小，根据其药代动力学特征。利伐沙班在CTPB和C中基于显著的药代动力学改变被归类为“不安全”。由于缺乏数据,阿哌沙班,Dabigatran和edoxaban被归类为CTPC的“未知”。
结论：DOAC可用于CTPA肝硬化患者，和阿哌沙班,Dabigatran和edoxaban也可以用于CTPB。建议在CTPB和C中避免使用利伐沙班。没有足够的证据支持在CTPC肝硬化中安全使用其他DOAC。
方法：我们进行了系统的文献检索，以确定有关药代动力学的研究，肝硬化DOAC的药效学和安全性。使用Child-Turcotte-Pugh（CTP）分类，根据肝硬化的严重程度收集数据并在汇总表中显示。一个多学科专家小组评估了结果，并根据安全性对DOAC进行了分类。
结果：纳入54项研究。所有DOAC被归类为“CTPA没有已知的额外风险”。对于CTPB，阿哌沙班,dabigatran和edoxaban被归类为“没有已知的额外风险”。阿哌沙班和依度沙班显示肝硬化患者的不良事件较少，而达比加群可能受到肝硬化严重程度的影响较小，根据其药代动力学特征。利伐沙班在CTPB和C中基于显著的药代动力学改变被归类为“不安全”。由于缺乏数据,阿哌沙班,Dabigatran和edoxaban被归类为CTPC的“未知”。
结论：DOAC可用于CTPA肝硬化患者，和阿哌沙班,Dabigatran和edoxaban也可以用于CTPB。建议在CTPB和C中避免使用利伐沙班。没有足够的证据支持在CTPC肝硬化中安全使用其他DOAC。
