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

Importance: Statin 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. Objective: To estimate the association of antecedent statin use with progression to severe inpatient outcomes among patients admitted for COVD-19. Design, setting and participants: We 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. Exposure: Antecedent statin use—statin prescription ≥ 30 days prior to COVID-19 admission. Main outcome: Composite end point of in-hospital death, intubation, and intensive care unit (ICU) admission. Results: Of 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 relevance: After 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.