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.

Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction.

BACKGROUND: People living with HIV are at risk of increased myocardial infarction (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV inflammation than other measures of VL, like baseline VL, but its associations with MI are not known. METHODS: The multisite Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort includes clinical data and centrally adjudicated MI with distinction between atheroembolic MI (type 1) and MI related to supply-demand mismatch (type 2). We examined CNICS participants who were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days of virus) from 6 months after enrollment was estimated with a time-weighted sum using the trapezoidal rule. We modeled associations of cumulative and baseline VL with MI by type using marginal structural Cox models. We contrasted the 75% percentile of the VL distribution with the 25% percentile. RESULTS: Among 11,324 participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR = 1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60; 95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI (HR = 1.51; 95% CI = 1.10, 2.08). CONCLUSIONS: Higher cumulative and baseline VL is associated with all MI, with a particularly strong association between cumulative VL and type 2 MI.