Statin Intake and All-Cause Mortality among Older Nursing Home Residents

Spiegeleer, Anton De; Migerode, Jordi Van; Bronselaer, Antoon; Wynendaele, Evelien; Peelman, Milan; Vandaele, Filip; Byttebier, Geert; Tré, Guy De; Belmans, Luc; Wiele, Christophe Van de; Sathekge, Mike; Dijck, Diemer Van; Saxberg, Bo E.H.; Alexander, Mathew; Fedson, David S.; Elewaut, Dirk; Noortgate, Nele Van Den; Spiegeleer, Bart De

doi:10.1159/000516862

Cited by 4 publications

(1 citation statement)

References 10 publications

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“…In the case of bacterial infection, it has been suggested that the activity of simvastatin is linked to its hydrophobicity, which may perturb the bacterial cell membrane compared to the more hydrophilic fluvastatin and pravastatin [ 49 ]. The hydrophobicity of statins is also one characteristic that can influence their target-binding characteristics and pharmacokinetic profile, potentially impacting how statins act on a multitude of organ systems and disease states [ 50 ]. Critically, the pro-drug form of simvastatin, predicted computationally and tested in our in vitro assays, is rapidly metabolized to its active acid form in vivo and therefore only a fraction of the total dose is maintained as the original pro-drug.…”

Section: Discussionmentioning

confidence: 99%

Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients

et al. 2023

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Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying therapeutic benefit. A Bayesian network tool was used to predict drugs that shift the host transcriptomic response to SARS-CoV-2 infection towards a healthy state. Drugs were predicted using 14 RNA-sequencing datasets from 72 autopsy tissues and 465 COVID-19 patient samples or from cultured human cells and organoids infected with SARS-CoV-2. Top drug predictions included statins, which were then assessed using electronic medical records containing over 4,000 COVID-19 patients on statins to determine mortality risk in patients prescribed specific statins versus untreated matched controls. The same drugs were tested in Vero E6 cells infected with SARS-CoV-2 and human endothelial cells infected with a related OC43 coronavirus. Simvastatin was among the most highly predicted compounds (14/14 datasets) and five other statins, including atorvastatin, were predicted to be active in > 50% of analyses. Analysis of the clinical database revealed that reduced mortality risk was only observed in COVID-19 patients prescribed a subset of statins, including simvastatin and atorvastatin. In vitro testing of SARS-CoV-2 infected cells revealed simvastatin to be a potent direct inhibitor whereas most other statins were less effective. Simvastatin also inhibited OC43 infection and reduced cytokine production in endothelial cells. Statins may differ in their ability to sustain the lives of COVID-19 patients despite having a shared drug target and lipid-modifying mechanism of action. These findings highlight the value of target-agnostic drug prediction coupled with patient databases to identify and clinically evaluate non-obvious mechanisms and derisk and accelerate drug repurposing opportunities.

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Section: Discussionmentioning

confidence: 99%

Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients

et al. 2023

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Potential role of statins in treatment of acute sarcopenia

et al. 2023

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The impact of statin use on short-term and long-term mortality in patients with heart failure

Zheng,

Tan,

Zhang

2024

Front. Pharmacol.

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BackgroundHeart failure (HF) is a complex disorder that has an association with increased morbidity and mortality rates globally. The association of statin use with mortality rate in individuals with HF remains unclear.ObjectivesTo examine the association of statin use with the short-term and long-term all-cause mortality rate in critically ill individuals with HF.MethodsWe performed a retrospective cohort analysis based on the Medical Information Mart for Intensive Care (MIMIC)-IV database. The critically ill people with HF were assigned to a statin group and a non-statin group according to whether they had been treated with statin or not during hospitalization. The Kaplan−Meier (KM) method and Cox proportional hazard models were adopted to explore the link between statin administration and the 30-day, 90-day, as well as 1-year mortality rates. To ensure the robustness of the findings, a 1:1 nearest propensity-score matching (PSM) was also performed.ResultsThe current research included 11,381 patients for the final analysis, with 7,561 in the statin group and 3,820 in the non-statin group. After multiple confounders were adjusted, we found that the Cox regression models revealed great beneficial effects of statin therapy on the 30-day, 90-day, as well as 1-year mortality rates among critically ill individuals with HF in the fully adjusted model. PSM also achieved consistent results. After PSM, the risk of mortality reduced by 23% for the 30-day mortality (HR = 0.77, 95%CI: 0.68–0.88, p < 0.001), 16% for the 90-day mortality rate (HR = 0.84, 95%CI: 0.75–0.93, p < 0.001), and 12% for the 1-year mortality rate (HR = 0.88, 95%CI: 0.81–0.97, p = 0.007). Patients treated with rosuvastatin had the greatest reduction in mortality rate. The 30-day, 90-day, and 1-year all-cause mortality rates were remarkably lower in patients who were treated with low-dose statins.ConclusionOur study unveiled that statin use was related to decreased short-term and long-term all-cause mortality rates in critically ill individuals with HF. Rosuvastatin was associated with the greatest reduction of all-cause mortality rates. Low-dose statins can significantly reduce short-term and long-term mortality, while high-dose statins are not significantly correlated with mortality. However, the results are not conclusive and should be interpreted with caution.

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Statin Intake and All-Cause Mortality among Older Nursing Home Residents

Cited by 4 publications

References 10 publications

Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients

Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients

Potential role of statins in treatment of acute sarcopenia

The impact of statin use on short-term and long-term mortality in patients with heart failure

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