Effect of Stains on LDL Reduction and Liver Safety: A Systematic Review and Meta-Analysis

Liang, Xiao; He, Qin; Zhao, Qinghua

doi:10.1155/2018/7092414

Cited by 11 publications

(4 citation statements)

References 51 publications

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“…Contrary to our and previous studies, a meta-analysis by Liang et al [33] suggested that statin use is associated with a significant increase in the risk of developing liver injury by 18%. However, there was no clear relationship between the dose or the lipid-lowering efficacy of different statins.…”

Section: Discussioncontrasting

confidence: 99%

Statin therapy in chronic viral hepatitis: a systematic review and meta-analysis of nine studies with 195,602 participants

et al. 2021

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Background: Conflicting data suggest that statins could cause chronic liver disease in certain group of patients, while improving prognosis in those with chronic viral hepatitis (CVH). Purpose: To quantify the potential protective role of statins on some main liver-related health outcomes in clinical studies on CVH patients.Purpose: Data Sources: The search strategy was explored by a medical librarian using bibliographic databases, from January 2015 to April 2020. Purpose: Data synthesis: The results showed no significant difference in the risk of mortality between statin users and non-users in the overall analysis. However, the risk of mortality significantly reduced by 39% in statin users who were followed for more than three years. Moreover, the risk of HCC, fibrosis, and cirrhosis in those on statins decreased by 53%, 45% and 41%, respectively. Although ALT and AST reduced slightly following statin therapy, this reduction was not statistically significant. Limitations: A significant heterogeneity among studies was observed, resulting from differences in clinical characteristics between statin users and non-users, study designs, population samples, diseases stage, comorbidities, and confounding covariates. Conclusion: Not only long-term treatment with statins seems to be safe in patients affected by hepatitis, but also it significantly improves their prognosis.

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Section: Discussioncontrasting

confidence: 99%

Statin therapy in chronic viral hepatitis: a systematic review and meta-analysis of nine studies with 195,602 participants

et al. 2021

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“…Among subjects taking tolvaptan1statin, incidences of statin-related adverse events were not statistically different than those observed with placebo1statin. Statin use is associated with increased risk for musculoskeletal toxicity and liver enzyme elevations, and gastrointestinal symptoms are commonly reported (18)(19)(20). No significant increases in statin-related musculoskeletal events or gastrointestinal symptoms were seen in the tolvaptan1statin groups versus the placebo1statin groups across the TEMPO 3:4 and REPRISE studies, suggesting no increased risk of these adverse events in patients receiving tolvaptan and a statin.…”

Section: Discussionmentioning

confidence: 95%

A Post Hoc Analysis of Statin Use in Tolvaptan Autosomal Dominant Polycystic Kidney Disease Pivotal Trials

Shoaf¹,

Sergeyeva²,

Estilo³

et al. 2020

CJASN

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Background and objectivesTolvaptan is approved to slow kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. Because in vitro studies indicated that the tolvaptan oxobutyric acid metabolite inhibits organic anion–transporting polypeptide (OATP)1B1 and OATP1B3, United States prescribing information advises avoiding concurrent use with OATP1B1/1B3 substrates, including hepatic hydroxymethyl glutaryl–CoA reductase inhibitors (statins). This post hoc analysis of the pivotal phase 3 tolvaptan trials (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes [TEMPO] 3:4 trial [NCT00428948] and Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD [REPRISE] trial [NCT02160145]) examined the safety of concurrent tolvaptan/statin use.Design, setting, participants, & measurementsThe trials randomized a combined total of 2815 subjects with early- to late-stage ADPKD to tolvaptan (n=1644) or placebo (n=1171) for 3 years (TEMPO 3:4) and 1 year (REPRISE). Statin use was unrestricted, and 597 subjects (21.2% overall; 332 [20.2%] tolvaptan, 265 [22.6%] placebo) received statins. Statin use (duration, dose change, statin change, permanent discontinuation), incidences of statin-related adverse events, and hepatic transaminase elevations were determined for subjects who received tolvaptan+statin, placebo+statin, tolvaptan alone, and placebo alone.ResultsNo differences in statin use parameters between tolvaptan- and placebo-treated subjects were observed. No statistically significant increases in commonly reported statin-related adverse events (e.g., musculoskeletal disorders, gastrointestinal symptoms) were seen between subjects receiving tolvaptan+statin and placebo+statin. For example, in TEMPO 3:4, frequencies were 5.4% and 7.8%, respectively, for myalgia (difference −2.4%; 95% confidence interval, −11.2% to 6.4%) and 9.3% and 7.8%, respectively, for abdominal pain (difference 1.5%; −7.9% to 10.9%). In an analysis that excluded participants concurrently using allopurinol, the frequency of alanine transaminase or aspartate transaminase >3× upper limit of normal in the pooled study populations was 3.6% for the tolvaptan+statin group and 2.3% for the placebo+statin group (difference 1.4%; −2.0% to 4.7%).ConclusionsTolvaptan has been used safely in combination with statins in clinical trials.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_04_06_CJN.08170719.mp3

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“…A meta-analysis of twenty-one clinical trials also reported significant elevations in liver enzyme concentrations in all of these trials (p < 0.05) (43). Another meta-analysis highlighted an increased risk of liver injury in individuals using statins, particularly among those using fluvastatin (44).…”

Section: Discussionmentioning

confidence: 98%

The effects of L-carnitine in reducing hepatotoxicity of statins in rats

Ibrahim,

Bader,

Bader

2023

Medicinski časopis

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Objective. The first line of treatment for hyperlipidemia is statins. In this group, atorvastatin is the most popular and effective drug. Hepatic toxicity and myopathy are the two observed adverse effects of statins. The active form of carnitine is L-carnitine, a water-soluble compound found in food, the body, and the majority of dietary supplements. There are many uses for L-carnitine in the human body. It assists in the removal of free radicals from the body and lowers hydrogen peroxide production, both of which may guard against liver side effects brought on by statins. Methods. Eighty rats were randomly divided into four main groups: control, L-carnitine, atorvastatin, and combination (L-carnitine + atorvastatin) groups. These groups were subdivided into three subgroups based on different doses of the drugs. The L-carnitine group was divided into L200, L300, and L400. The atorvastatin group was divided into A10, A15, and A20. The combination group was subdivided into AL10/200, AL15/300, and AL20/400. All groups received their treatments daily for one month. Results. According to our findings, the effects of L-carnitine (200 mg/kg daily) on the increase in AST brought on by atorvastatin are not statistically significant, although they are significant on the increases in ALT, ALP and TSB. L-carnitine still has substantial impacts on ALT, ALP and TSB even at larger doses, while its impacts on AST levels had become significant. Conclusion. Our research highlights the beneficial effects of supplementing with L-carnitine over a four-week period, which effectively mitigates the liver damage caused by atorvastatin.

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Effect of Stains on LDL Reduction and Liver Safety: A Systematic Review and Meta-Analysis

Cited by 11 publications

References 51 publications

Statin therapy in chronic viral hepatitis: a systematic review and meta-analysis of nine studies with 195,602 participants

Statin therapy in chronic viral hepatitis: a systematic review and meta-analysis of nine studies with 195,602 participants

A Post Hoc Analysis of Statin Use in Tolvaptan Autosomal Dominant Polycystic Kidney Disease Pivotal Trials

The effects of L-carnitine in reducing hepatotoxicity of statins in rats

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