Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study
Henry C Cousins, M.D Russ B Altman
doi:10.1101/2023.02.28.23286515
Background: Spironolactone has been proposed as a potential modulator of SARS-CoV-2 cellular entry. We aimed to measure the effect of spironolactone use on the risk of adverse outcomes following COVID-19 hospitalization.
Methods: We performed a retrospective cohort study of COVID-19 outcomes for patients with or without exposure to spironolactone, using population-scale claims data from the Komodo Healthcare Map. We identified all patients with a hospital admission for COVID-19 in the study window, defining treatment status based on spironolactone prescription orders. The primary outcomes were progression to respiratory ventilation or mortality during the hospitalization. Odds ratios (OR) were estimated following either 1:1 propensity score matching (PSM) or multivariable regression. Subgroup analysis was performed based on age, gender, body mass index (BMI), and dominant SARS-CoV-2 variant. Findings: Among 898,303 eligible patients with a COVID-19-related hospitalization, 16,324 patients (1.8%) had a spironolactone prescription prior to hospitalization. 59,937 patients (6.7%) met the ventilation endpoint, and 26,515 patients (3.0%) met the mortality endpoint. Spironolactone use was associated with a significant reduction in odds of both ventilation (OR 0.82; 95% CI: 0.75-0.88; p < 0.001) and mortality (OR 0.88; 95% CI: 0.78-0.99; p = 0.033) in the PSM analysis, supported by the regression analysis. Spironolactone use was associated with significantly reduced odds of NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
AUTHOR CONTRIBUTIONS Both HCC and RBA contributed to all aspects of the manuscript (conceptualization, data acquisition, analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation, visualization, drafting the manuscript, and reviewing the manuscript). Both HCC and RBA directly accessed and verified the underlying data.
DECLARATION OF INTERESTS No authors declare any competing interests.
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'abstract': '<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Spironolactone '
'has been proposed as a potential modulator of SARS-CoV-2 cellular entry. We aimed to measure '
'the effect of spironolactone use on the risk of adverse outcomes following COVID-19 '
'hospitalization.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We '
'performed a retrospective cohort study of COVID-19 outcomes for patients with or without '
'exposure to spironolactone, using population-scale claims data from the Komodo Healthcare '
'Map. We identified all patients with a hospital admission for COVID-19 in the study window, '
'defining treatment status based on spironolactone prescription orders. The primary outcomes '
'were progression to respiratory ventilation or mortality during the hospitalization. Odds '
'ratios (OR) were estimated following either 1:1 propensity score matching (PSM) or '
'multivariable regression. Subgroup analysis was performed based on age, gender, body mass '
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'variant.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>Among 898,303 '
'eligible patients with a COVID-19-related hospitalization, 16,324 patients (1.8%) had a '
'spironolactone prescription prior to hospitalization. 59,937 patients (6.7%) met the '
'ventilation endpoint, and 26,515 patients (3.0%) met the mortality endpoint. Spironolactone '
'use was associated with a significant reduction in odds of both ventilation (OR 0.82; 95% CI: '
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'significantly reduced odds of ventilation for all age groups, men, women, and non-obese '
'patients, with the greatest protective effects in younger patients, men, and non-obese '
'patients.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Spironolactone '
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'ventilation and consistent with an androgen-dependent mechanism. The findings warrant '
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