Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Alberta Health Services, Edmonton, AB, Canada.
BMC Gastroenterol. 2021 Mar 16;21(1):120. doi: 10.1186/s12876-021-01704-w.
BACKGROUND/AIMS: There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review we aimed to address pharmacokinetics (PK), safety, and effects on cardiovascular (CV) outcomes of statins in cirrhosis.
Our systematic search in several electronic databases and repositories of two regulatory bodies up to 2020-06-11 yielded 22 articles and 2 drug monographs with relevant data.
Rosuvastatin and pitavastatin showed minimal PK changes in Child-Pugh A cirrhosis. Only rosuvastatin was assessed in a repeated dosing PK study. Atorvastatin showed pronounced PK changes in cirrhosis. No PK data was found for simvastatin, the most commonly used statin in cirrhosis trials. There was insufficient data to assess CV effects of statins in cirrhosis. Clinical trials in cirrhosis were limited to simvastatin, atorvastatin, and pravastatin. In patients taking simvastatin 40 mg, pooled frequency of rhabdomyolysis was 2%, an incidence 40-fold higher than that reported in non-cirrhosis patients, while this was no rhabdomyolysis observed in patients on simvastatin 20 mg, atorvastatin 20 mg, or pravastatin 40 mg. Drug-induced liver injury was of difficult interpretation due to co-existence of muscle damage. No overt liver failure was reported.
Simvastatin 40 mg should be avoided in decompensated cirrhosis. Safety data on simvastatin 20 mg or other statins are based on small study sample size. This rarity of evidence combined with lack of data in dose adjustment methods in cirrhosis is a barrier for using statins for CV indications or for investigational use for liver indications.
背景/目的：人们对他汀类药物在肝硬化中的治疗应用越来越感兴趣，但首选的他汀类药物和安全性结果仍不清楚。在本系统评价中，我们旨在探讨他汀类药物在肝硬化中的药代动力学（PK）、安全性和对心血管（CV）结局的影响。
我们在多个电子数据库和两个监管机构的存储库中进行了系统搜索，检索截至 2020 年 6 月 11 日的相关数据，共获得 22 篇文章和 2 篇药物专论。
在 Child-Pugh A 级肝硬化中，瑞舒伐他汀和匹伐他汀的 PK 变化最小。只有瑞舒伐他汀在重复剂量 PK 研究中进行了评估。阿托伐他汀在肝硬化中表现出明显的 PK 变化。在肝硬化试验中最常用的他汀类药物辛伐他汀未发现 PK 数据。由于缺乏数据，无法评估他汀类药物在肝硬化中的 CV 效应。肝硬化的临床试验仅限于辛伐他汀、阿托伐他汀和普伐他汀。在服用辛伐他汀 40mg 的患者中，横纹肌溶解的发生率为 2%，是未患肝硬化患者报告发生率的 40 倍，而服用辛伐他汀 20mg、阿托伐他汀 20mg 或普伐他汀 40mg 的患者则未观察到横纹肌溶解。由于肌肉损伤的存在，药物性肝损伤的解释较为困难。未报告明显的肝衰竭。
失代偿期肝硬化应避免使用辛伐他汀 40mg。关于辛伐他汀 20mg 或其他他汀类药物的安全性数据基于小样本量的研究。这种证据罕见，再加上肝硬化中缺乏剂量调整方法的数据，这是在 CV 适应证中使用他汀类药物或在肝脏适应证中进行研究性使用的障碍。
