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0 0.5 1 1.5 2+ Mortality, 90 day exposure 18% Improvement Relative Risk Mortality, 180 day expos.. 12% primary Mortality, 360 day expos.. 15% Ventilation, 90 day expo.. 17% Ventilation, 180 day exp.. 17% primary Ventilation, 360 day exp.. 10% Spironolactone  Cousins et al.  Prophylaxis Is prophylaxis with antiandrogens beneficial for COVID-19? PSM retrospective 898,303 patients in the USA Lower mortality (p=0.0038) and ventilation (p<0.0001) Cousins et al., medRxiv, March 2023 Favors spironolactone Favors control

Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study

Cousins et al., medRxiv, doi:10.1101/2023.02.28.23286515
Mar 2023  
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5th treatment shown to reduce risk in August 2020
*, now known with p = 0.000000043 from 50 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments.
PSM retrospective 898,303 hospitalized COVID-19 patients in the USA, 16,324 on spironolactone, showing lower mortality and ventilation with spironolactone use.
risk of death, 18.4% lower, RR 0.82, p = 0.004, treatment 390 of 12,504 (3.1%), control 479 of 12,504 (3.8%), NNT 140, odds ratio converted to relative risk, 90 day exposure window, propensity score matching.
risk of death, 11.6% lower, RR 0.88, p = 0.04, treatment 521 of 16,324 (3.2%), control 592 of 16,324 (3.6%), NNT 230, odds ratio converted to relative risk, 180 day exposure window, propensity score matching, primary outcome.
risk of death, 14.5% lower, RR 0.85, p = 0.003, treatment 671 of 20,690 (3.2%), control 783 of 20,690 (3.8%), NNT 185, odds ratio converted to relative risk, 360 day exposure window, propensity score matching.
risk of mechanical ventilation, 16.7% lower, RR 0.83, p < 0.001, treatment 936 of 12,504 (7.5%), control 1,118 of 12,504 (8.9%), NNT 69, odds ratio converted to relative risk, 90 day exposure window, propensity score matching.
risk of mechanical ventilation, 16.7% lower, RR 0.83, p < 0.001, treatment 1,212 of 16,324 (7.4%), control 1,459 of 16,324 (8.9%), NNT 66, odds ratio converted to relative risk, 180 day exposure window, propensity score matching, primary outcome.
risk of mechanical ventilation, 10.2% lower, RR 0.90, p < 0.001, treatment 1,524 of 20,690 (7.4%), control 1,701 of 20,690 (8.2%), NNT 117, odds ratio converted to relative risk, 360 day exposure window, propensity score matching.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Cousins et al., 2 Mar 2023, retrospective, propensity score matching, USA, peer-reviewed, 2 authors.
This PaperAntiandrogensAll
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
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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