The Association Between the Use of Statins and Clinical Outcomes in Patients with COVID-19: A Systematic Review and Meta-analysis

Abstract

Purpose Previously, we have reported potential clinical benefits with the use of statins in patients with coronavirus disease 2019 (COVID-19) in a meta-analysis, where there was a significantly reduced hazard for a fatal or severe course of illness with the use of statins, but the meta-analysis was limited by the small number of studies included, with small heterogeneity among studies, due to the unavailability of more studies at the point of literature search. We aimed to perform an updated systematic review and meta-analysis to summarize the existing evidence on the effect of statins on the clinical outcomes of patients with COVID-19. Methods Electronic databases, including PubMed, Google Scholar, and Scopus, and preprint servers were searched (last updated June 3, 2021) to identify studies investigating the association between the use of statins in patients with COVID-19 and the development of severe disease and/or mortality. Random-effects model meta-analyses were performed to estimate the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CIs). The outcomes of interest were (1) all-cause mortality and (2) a composite endpoint of severe illness of COVID-19. Results Upon systematic literature search, we identified 35 studies, of which 32 studies reported the outcome of all-cause mortality and 15 studies reported the composite endpoint of severe COVID-19 illness between statin users versus non-statin users with COVID-19. Our meta-analysis revealed that the use of statins was associated with a significantly lower risks of all-cause mortality (HR = 0.70, 95% CI 0.58–0.84, n = 21,127, and OR = 0.63, 95% CI 0.51–0.79, n = 115,097) and the composite endpoint of severe illness (OR = 0.80, 95% CI 0.73–0.88, n = 10,081) in patients with COVID-19, compared to non-use of statins, at the current sample size. Conclusion Statin use is associated with a better prognosis in patients with COVID-19. Our findings provide a rationale to investigate the use of statins among patients with COVID-19 in large scale clinical trials.

Respiratory Tract Infections in Diabetes – Lessons From Tuberculosis and Influenza to Guide Understanding of COVID-19 Severity

“…With regards to controlling dyslipidemia, the most commonly used class of drugs is Statins and studies have been ambivalent. Some meta-analyses conclude better outcome from retrospective studies ( 189 ) whilst others report improvement, worsening or no effect ( 190 ).…”

Discontinuation of atorvastatin use in hospital is associated with increased risk of mortality in COVID‐19 patients

“…A meta‐analysis of 13 observational studies found a 27% reduction in negative clinical outcomes, when adjusting for confounding variables, namely in‐hospital mortality or severe disease 14 . Another meta‐analysis confirmed the association of statin use with lower risk of all‐cause mortality and severe illness, but noted the limitations of sample size and heterogeneity between studies 15 . This suggests that further analysis and controlled trials are needed to better understand the potential of statins as a COVID‐19 treatment…”

“…14 Another meta-analysis confirmed the association of statin use with lower risk of all-cause mortality and severe illness, but noted the limitations of sample size and heterogeneity between studies. 15 This suggests that further analysis and controlled trials are needed to better understand the potential of statins as a COVID-19 treatment | 173…”

In Vitro Evidence of Statins’ Protective Role against COVID-19 Hallmarks

“…However, since statins are drugs prescribed for patients with cardiovascular complications that constitute predisposing factors for SARS-CoV-2 infection, the results from these observational studies are often controversial due to multiple confounding factors and clinical bias influencing data interpretation [ 39 ]. Despite this, the overall conclusion emerging so far from several meta-analyses is that statins used in COVID-19 patients is associated with improved clinical outcomes and reduced Intensive Care Unit (ICU) admission, mechanical intubation, ARDS, and in-hospital death [ 20 , 40 , 41 , 42 ]. The studies included in these meta-analyses and emerging observational studies [ 43 , 44 ] strongly suggest that statin therapy exerts a protective effect against complications from COVID-19, preventing the worst prognosis.…”