Maaike M E Diesveld, Daniëlle W M Jacobs- Pijnenburg, Rianne A Weersink, Ina Barzel, Joost P H Drenth, Ton Lisman, Herold J Metselaar, Margje H Monster-Simons, Midas B Mulder, Eline Okel, Katja Taxis, Sander D Borgsteede
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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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data.\",\"authors\":\"Maaike M E Diesveld, Daniëlle W M Jacobs- Pijnenburg, Rianne A Weersink, Ina Barzel, Joost P H Drenth, Ton Lisman, Herold J Metselaar, Margje H Monster-Simons, Midas B Mulder, Eline Okel, Katja Taxis, Sander D Borgsteede\",\"doi\":\"10.1007/s00228-024-03648-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. 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There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.</p>\",\"PeriodicalId\":11857,\"journal\":{\"name\":\"European Journal of Clinical Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Clinical Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00228-024-03648-y\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00228-024-03648-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/2 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
目的：直接口服抗凝药（DOAC）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很大影响，可能会增加不良反应。肝硬化患者安全用药需要认真进行风险效益分析。本研究的目的是在系统回顾药代动力学、药效学和安全性数据的基础上，为肝硬化患者安全使用 DOACs 制定实践建议：我们进行了系统性文献检索，以确定有关肝硬化患者 DOACs 药代动力学、药效学和安全性的研究。我们收集了相关数据，并按照Child-Turcotte-Pugh (CTP)分类法以肝硬化严重程度汇总表的形式展示了这些数据。一个多学科专家小组对结果进行了评估，并根据安全性对 DOACs 进行了分类：结果：共纳入 54 项研究。在 CTP A 中，所有 DOAC 均被归类为 "无已知额外风险"。对于 CTP B，阿哌沙班、达比加群和埃多沙班被归类为 "无已知额外风险"。阿哌沙班和埃多沙班在肝硬化患者中发生的不良事件较少，而达比加群则根据其药代动力学特征可能受肝硬化严重程度的影响较小。利伐沙班在 CTP B 和 C 中被列为 "不安全 "药物，因为其药代动力学发生了重大改变。由于缺乏数据，阿哌沙班、达比加群和依多沙班在 CTP C 中被列为 "未知"：阿哌沙班、达比加群和依多沙班也可用于 CTP B。
Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data.
Purpose: 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.
Conclusion: 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.
期刊介绍：
The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed.
Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor.
Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves
-a compound that is interesting and new in some basic or fundamental way, or
-methods that are original in some basic sense, or
-a highly unexpected outcome, or
-conclusions that are scientifically novel in some basic or fundamental sense.
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