Cargando…

A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis

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 cirrh...

Descripción completa

Detalles Bibliográficos
Autores principales: Sung, Shuen, Al-Karaghouli, Mustafa, Kalainy, Sylvia, Cabrera Garcia, Lourdes, Abraldes, Juan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967963/
https://www.ncbi.nlm.nih.gov/pubmed/33726685
http://dx.doi.org/10.1186/s12876-021-01704-w
_version_ 1783665978347880448
author Sung, Shuen
Al-Karaghouli, Mustafa
Kalainy, Sylvia
Cabrera Garcia, Lourdes
Abraldes, Juan G.
author_facet Sung, Shuen
Al-Karaghouli, Mustafa
Kalainy, Sylvia
Cabrera Garcia, Lourdes
Abraldes, Juan G.
author_sort Sung, Shuen
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-021-01704-w.
format Online
Article
Text
id pubmed-7967963
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-79679632021-03-22 A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis Sung, Shuen Al-Karaghouli, Mustafa Kalainy, Sylvia Cabrera Garcia, Lourdes Abraldes, Juan G. BMC Gastroenterol Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-021-01704-w. BioMed Central 2021-03-16 /pmc/articles/PMC7967963/ /pubmed/33726685 http://dx.doi.org/10.1186/s12876-021-01704-w Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Sung, Shuen
Al-Karaghouli, Mustafa
Kalainy, Sylvia
Cabrera Garcia, Lourdes
Abraldes, Juan G.
A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis
title A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis
title_full A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis
title_fullStr A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis
title_full_unstemmed A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis
title_short A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis
title_sort systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967963/
https://www.ncbi.nlm.nih.gov/pubmed/33726685
http://dx.doi.org/10.1186/s12876-021-01704-w
work_keys_str_mv AT sungshuen asystematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis
AT alkaraghoulimustafa asystematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis
AT kalainysylvia asystematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis
AT cabreragarcialourdes asystematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis
AT abraldesjuang asystematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis
AT sungshuen systematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis
AT alkaraghoulimustafa systematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis
AT kalainysylvia systematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis
AT cabreragarcialourdes systematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis
AT abraldesjuang systematicreviewonpharmacokineticscardiovascularoutcomesandsafetyprofilesofstatinsincirrhosis