Association of statin use with outcomes of patients admitted with COVID-19: an analysis of electronic health records using superlearner

QuestionIs statin use prior to hospital admission for COVID-19 associated with reducing severe inpatient outcomes?FindingsIn this observational study using electronic health records from a multi-hospital health system in Chicago, we used robust statistical methods to account for confounding and found that adults 40 years or older who were prescribed statins prior to admission for COVID-19 had minimally lower rates of intubation and admission to the intensive care unit. However, inpatient mortality was comparable between statins users and non-users.MeaningConsistent with current COVID-19 treatment guidelines, we did not find evidence supporting the utilization of statins for clinically significant reduction in severe inpatient COVID-19 outcomes. ImportanceStatin use prior to hospitalization for Coronavirus Disease 2019 (COVID-19) is hypothesized to improve inpatient outcomes including mortality, but prior findings from large observational studies have been inconsistent, due in part to confounding. Recent advances in statistics, including incorporation of machine learning techniques into augmented inverse probability weighting with targeted maximum likelihood estimation, address baseline covariate imbalance while maximizing statistical efficiency.ObjectiveTo estimate the association of antecedent statin use with progression to severe inpatient outcomes among patients admitted for COVD-19.Design, setting and participantsWe retrospectively analyzed electronic health records (EHR) from individuals >= 40-years-old who were admitted between March 2020 and September 2022 for >= 24 h and tested positive for SARS-CoV-2 infection in the 30 days before to 7 days after admission.ExposureAntecedent statin use-statin prescription >= 30 days prior to COVID-19 admission.Main outcomeComposite end point of in-hospital death, intubation, and intensive care unit (ICU) admission.ResultsOf 15,524 eligible COVID-19 patients, 4412 (20%) were antecedent statin users. Compared with non-users, statin users were older (72.9 (SD: 12.6) versus 65.6 (SD: 14.5) years) and more likely to be male (54% vs. 51%), White (76% vs. 71%), and have >= 1 medical comorbidity (99% vs. 86%). Unadjusted analysis demonstrated that a lower proportion of antecedent users experienced the composite outcome (14.8% vs 19.3%), ICU admission (13.9% vs 18.3%), intubation (5.1% vs 8.3%) and inpatient deaths (4.4% vs 5.2%) compared with non-users. Risk differences adjusted for labs and demographics were estimated using augmented inverse probability weighting with targeted maximum likelihood estimation using Super Learner. Statin users still had lower rates of the composite outcome (adjusted risk difference: - 3.4%; 95% CI: - 4.6% to - 2.1%), ICU admissions (- 3.3%; - 4.5% to - 2.1%), and intubation (- 1.9%; - 2.8% to - 1.0%) but comparable inpatient deaths (0.6%; - 1.3% to 0.1%).Conclusions and relevanceAfter controlling for confounding using doubly robust methods, antecedent statin use was associated with minimally lower risk of severe COVID-19-related outcomes, ICU admission and intubation, however, we were not able to corroborate a statin-associated mortality benefit.

Automated summary

In this observational study, it was found that pre-hospital statin use in COVID-19 patients aged 40 and above was associated with slightly lower rates of intubation and ICU admission. However, there was no significant difference in inpatient mortality between statin users and non-users. Therefore, the current COVID-19 treatment guidelines do not support the use of statins for reducing severe inpatient outcomes.