Association of early statin initiation during COVID-19 admission with inpatient mortality at an academic health system in Illinois, March 2020 to September 2022: a target trial emulation using observational data

Objective We assessed the association of early statin initiation with inpatient mortality among hospitalised COVID-19 patients. Design, setting and participants This observational study emulated a hypothetical target trial using electronic health records data from Northwestern Medicine Health System, Illinois, 2020–2022. We included patients who were ≥40 years, admitted ≥48 hours for COVID-19 from March 2020 to August 2022 and had no evidence of statin use before admission. Interventions Individuals who initiated any statins within 48 hours of admission were compared with individuals who did not initiate statins during this period. Primary outcome measures Inpatient mortality at hospital days 7, 14, 21 and 28 were determined using hospital records. Risk differences between exposure groups were calculated using augmented inverse propensity weighting (AIPW) with SuperLearner. Results A total of 8893 individuals (24.5% early statin initiators) were included. Early initiators tended to be older, male and have higher comorbidity burdens. Unadjusted day 28 mortality was higher in early initiators (6.0% vs 3.6%). Adjusted analysis showed slightly higher inpatient mortality risk at days 7 (RD: 0.5%, 95% CI: 0.2 to 0.8) and 21 (RD: 0.6%, 95% CI: 0.04 to 1.1), but not days 14 (RD: 0.4%, 95% CI: −0.03 to 0.9) and 28 (RD: 0.4%, 95% CI: −0.2 to 1.1). Sensitivity analyses using alternative modelling approaches showed no difference between groups. Conclusions Early statin initiation was not associated with lower mortality contrasting with findings of previous observational studies. Trial emulation helped in identifying and addressing sources of bias incompletely addressed by previous work. Statin use may be indicated for other conditions but not COVID-19.