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Guideline-conform statin use reduces overall mortality in patients with compensated liver disease.

ABSTRACT: Statins reduce cardiovascular risk. However, "real-life" data on statin use in patients with chronic liver disease and its impact on overall and liver-related survival are limited. Therefore, we assessed 1265 CLD patients stratified as advanced (ACLD) or non-advanced (non-ACLD) stage. Statin indication was evaluated according to the 2013 ACC/AHA guidelines and survival-status was verified by national death registry data. Overall, 122 (9.6%) patients had an indication for statin therapy but did not receive statins, 178 (14.1%) patients were on statins and 965 (76.3%) patients had no indication for statins. Statin underutilization was 34.2% in non-ACLD and 48.2% in ACLD patients. In non-ACLD patients, survival was worse without a statin despite indication as compared to patients on statin or without indication (log-rank p = 0.018). In ACLD patients, statin use did not significantly impact on survival (log-rank p = 0.264). Multivariate cox regression analysis confirmed improved overall survival in patients with statin as compared to patients with indication but no statin (HR 0.225; 95%CI 0.053-0.959; p = 0.044) and a trend towards reduced liver-related mortality (HR 0.088; 95%CI 0.006-1.200; p = 0.068). This was not observed in ACLD patients. In conclusion, guideline-confirm statin use is often withhold from patients with liver disease and this underutilization is associated with impaired survival in non-ACLD patients.

SUBMITTER: Unger LW

PROVIDER: S-EPMC6690990 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Guideline-conform statin use reduces overall mortality in patients with compensated liver disease.

Unger Lukas W LW Forstner Bernadette B Schneglberger Stephan S Muckenhuber Moritz M Eigenbauer Ernst E Bauer David D Scheiner Bernhard B Mandorfer Mattias M Trauner Michael M Reiberger Thomas T

Scientific reports 20190812 1

Statins reduce cardiovascular risk. However, "real-life" data on statin use in patients with chronic liver disease and its impact on overall and liver-related survival are limited. Therefore, we assessed 1265 CLD patients stratified as advanced (ACLD) or non-advanced (non-ACLD) stage. Statin indication was evaluated according to the 2013 ACC/AHA guidelines and survival-status was verified by national death registry data. Overall, 122 (9.6%) patients had an indication for statin therapy but did n ...[more]

PMID: 31406146

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Project description:ImportanceGiven the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed.ObjectiveTo examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population.Design, setting, and participantsThis cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020. Individuals were matched using propensity score matching according to the following criteria: age, sex, body mass index, ethnicity, diabetes with or without insulin or biguanide use, hypertension, ischemic heart disease, dyslipidemia, aspirin use, and number of medications taken (UKB only). Data analysis was performed from April 2021 to April 2023.ExposureRegular statin use.Main outcomes and measuresPrimary outcomes were liver disease and HCC development as well as liver-associated death.ResultsA total of 1 785 491 individuals were evaluated after matching (aged 55 to 61 years on average, up to 56% men, and up to 49% women). A total of 581 cases of liver-associated death, 472 cases of incident HCC, and 98 497 new liver diseases were registered during the follow-up period. Individuals were aged 55-61 years on average, with a slightly higher proportion of men (up to 56%). In UKB individuals (n = 205 057) without previously diagnosed liver disease, statin users (n = 56 109) had a 15% lower hazard ratio (HR) for the association of developing a new liver disease (HR, 0.85; 95% CI, 0.78-0.92; P < .001). In addition, statin users demonstrated a 28% lower HR for the association with liver-related death (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and a 42% lower HR for the development of HCC (HR, 0.58; 95% CI, 0.35-0.96; P = .04). In TriNetX individuals (n = 1 568 794), the HR for the association of HCC was reduced even further for statin users (HR, 0.26; 95% CI, 0.22-0.31; P = .003). The hepatoprotective association of statins was time and dose dependent, with a significant association in PMBB individuals (n = 11 640) for incident liver diseases after 1 year of statin use (HR, 0.76; 95% CI, 0.59-0.98; P = .03). Taking statins was particularly beneficial in men, individuals with diabetes, and individuals with a high Fibrosis-4 index at baseline. Carriers of the heterozygous minor allele of PNPLA3 rs738409 benefited from statin use and had a 69% lower HR for the association with HCC (UKB HR, 0.31; 95% CI, 0.11-0.85; P = .02).Conclusions and relevanceThis cohort study indicates substantial preventive associations of statins against liver disease, with an association with duration and dose of intake.

Project description:Background 2018 American Heart Association/American College of Cardiology cholesterol guideline recommends statin in patients with chronic and/or stable liver disease for secondary prevention of atherosclerotic cardiovascular disease yet remains equivocal on the adequate intensity of statin for patients with chronic liver disease (CLD). We aimed to assess the association between statin intensity and mortality among patients with CLD with atherosclerotic cardiovascular disease. Methods and Results We conducted a population-based cohort study in South Korea. We assessed the risk of survival and clinical outcomes using inverse probability of treatment-weighted Cox proportional hazards regression. We also estimated the absolute risk difference between treatment groups based on the Poisson distribution. During an average of 2.35 person-years, 10 442 patients with CLD with atherosclerotic cardiovascular disease were identified. Among those patients, 5515 (52.8%) received high-intensity statin, and 4927 (47.2%) received low/moderate-intensity statin. High-intensity statin was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.83 [95% CI, 0.75-0.92]), cardiovascular-cause mortality (HR, 0.85 [0.71-1.01]), liver-cause mortality (HR, 0.72 [0.54-0.97]) compared with low/moderate-intensity statin. Although both hospitalizations for recurrent myocardial infarction and stroke were shown to be increased among high-intensity statin users, effect estimate was homogeneous in the absolute scale (myocardial infarction: HR, 1.12 [1.04-1.19], risk difference, 7.57 [-0.69 to 15.84] per 1000 person-years; stroke: HR, 1.11 [0.97 to 1.27]; risk difference, -1.70 [-5.19 to 1.78]). Conclusions Among patients with CLD with atherosclerotic cardiovascular disease, high-intensity statin was significantly associated with a lower risk of mortality. These findings herein support the guidelines for statin use in patients with CLD while demonstrating potential benefit of optimal intensity use.

Project description:BackgroundStatin use could benefit patients with non-alcoholic fatty liver disease (NAFLD), but the evidence is segmented and inconclusive. This multidimensional study comprehensively investigated the potential benefits and mechanism-of-action of statins in NAFLD.MethodsA cross-sectional investigation was performed within the Rotterdam Study (general population; n = 4.576) and the PERSONS cohort (biopsy-proven NAFLD patients; n = 569). Exclusion criteria were secondary causes for steatosis and insufficient data on alcohol, dyslipidemia or statin use. Associations of statin use with NAFLD (among entire general population), fibrosis and NASH (among NAFLD individuals and patients) were quantified. These results were pooled with available literature in meta-analysis. Last, we assessed statins' anti-lipid and anti-inflammatory effects in 3D cultured human liver organoids and THP-1 macrophages, respectively.FindingsStatin use was inversely associated with NAFLD in the Rotterdam study compared to participants with untreated dyslipidemia. In the PERSONS cohort, statin use was inversely associated with NASH, but not with fibrosis. The meta-analysis included 7 studies and indicated a not significant inverse association for statin use with NAFLD (pooled-Odds Ratio: 0.69, 95% Confidence Interval: 0.46-1.01) and significant inverse associations with NASH (pooled-OR: 0.59, 95% CI: 0.44-0.79) and fibrosis (pooled-OR: 0.48, 95% CI: 0.33-0.70). In vitro, statins significantly reduced lipid droplet accumulation in human liver organoids and downregulated expression of pro-inflammatory cytokines in macrophages.InterpretationPooled results demonstrated that statin use was associated with a lower prevalence of NASH and fibrosis and might prevent NAFLD. This may be partially attributed to the anti-lipid and anti-inflammatory characteristics of statins. Given their under-prescription, adequate prescription of statins may limit the disease burden of NAFLD.FundingZonMw, KWF, NWO, SLO, DGXII, RIDE, National and regional government, Erasmus MC and Erasmus University.

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Guideline-conform statin use reduces overall mortality in patients with compensated liver disease.

Publications

Guideline-conform statin use reduces overall mortality in patients with compensated liver disease.

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