Shuen Sung1, Mustafa Al-Karaghouli2, Sylvia Kalainy3, Lourdes Cabrera Garcia4, Juan G Abraldes5,6. 1. Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. ssung@ualberta.ca. 2. Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. 3. Alberta Health Services, Edmonton, AB, Canada. 4. Faculty of Medicine, Complutense University of Madrid, Madrid, Spain. 5. Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. juan.g.abraldes@ualberta.ca. 6. Division of Gastroenterology, 1-38 Zeidler Ledcor Centre, University of Alberta, 8540 112 St NW, Edmonton, AB, T6G 2X8, Canada. juan.g.abraldes@ualberta.ca.
Abstract
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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. METHODS: 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. RESULTS: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-cirrhosispatients, 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. CONCLUSIONS: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.
Authors: Samarth S Patel; Luis A Guzman; Fei-Pi Lin; Taylor Pence; Trevor Reichman; Binu John; Francesco S Celi; Erika Liptrap; Chandra Bhati; Mohammad S Siddiqui Journal: Liver Transpl Date: 2018-07 Impact factor: 5.799
Authors: C Baigent; L Blackwell; J Emberson; L E Holland; C Reith; N Bhala; R Peto; E H Barnes; A Keech; J Simes; R Collins Journal: Lancet Date: 2010-11-08 Impact factor: 79.321
Authors: Julian P T Higgins; Douglas G Altman; Peter C Gøtzsche; Peter Jüni; David Moher; Andrew D Oxman; Jelena Savovic; Kenneth F Schulz; Laura Weeks; Jonathan A C Sterne Journal: BMJ Date: 2011-10-18
Authors: Eric C Swei; Anantnoor K Brar; Jonathan D Rice; Ike I Kim; Virginia M Knez; Christopher F Doe; Lisa M Forman Journal: ACG Case Rep J Date: 2022-05-04