The effect of statins on mortality among patients with infection: umbrella review of meta-analyses

Objective: Although previous research has reported beneficial effects of statins on infectious diseases, these have yet to be concluded. Therefore, we conducted an umbrella review to provide a comprehensive understanding of the strength of evidence and validity of claimed associations between statins (hydroxymethyl glutaryl-CoA reductase inhibitors) and infectious diseases. Patients and methods: We conducted an umbrella review and re-analyzed data from meta-analyses of randomized controlled trials and observational studies on associations between statin use and different infectious diseases such as bacteremia/sepsis and pneumonia. We also evaluated the level of evidence for each re-analyzed outcome based on the criteria using p-values of random and fixed-effects, 95% prediction intervals, small-study effects, between-study heterogeneity, and concordance between the effect estimate of the largest study and summary estimates of the meta-analysis. Moreover, publication bias was also examined. Results: Through a systematic literature search, we obtained 14 eligible articles including 25 meta-analyses. All 4 meta-analyses on overall infection, 3 out of 14 meta-analyses on bacteremia/sepsis, and 5 out of 7 meta-analyses on pneumonia demonstrated that statin use was associated with reduced mortality due to infections (caused by infections). Nonetheless, most significant results only showed a weak level of evidence, and one study with convincing evidence prior to adjustment also showed weak evidence after adjustment. Conclusions: The present review identified a protective effect of statins on infection-related mortality, but all available studies had a weak level of evidence. Therefore, further studies with a strong level of evidence are needed, and it is also necessary to investigate the types of statins and to study clinical outcomes other than mortality to gain further insights.