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0 0.5 1 1.5 2+ Mortality 72% Improvement Relative Risk Wallace et al. Metformin for COVID-19 Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 8,173 patients in the USA Lower mortality with metformin (p<0.000001) Wallace et al., BMJ Open, doi:10.1136/bmjopen-2021-050051 Favors metformin Favors control
Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study
Wallace et al., BMJ Open, doi:10.1136/bmjopen-2021-050051
Wallace et al., Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based.., BMJ Open, doi:10.1136/bmjopen-2021-050051
Dec 2021   Source   PDF  
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Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing lower mortality with metformin use. The study provides results for use before, after, and before+after. Before+after should more accurately represent prophylaxis up to COVID-19 infection (and continued use). Before included use up to 2 years before, and after included use up to 60 days later.
risk of death, 72.0% lower, HR 0.28, p < 0.001, treatment 103 of 1,203 (8.6%), control 1,536 of 6,970 (22.0%), NNT 7.4, adjusted per study, before+after, propensity score weighting, Cox proportional hazards.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Wallace et al., 31 Dec 2021, retrospective, database analysis, USA, peer-reviewed, 6 authors.
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Abstract: Original research Association of the patterns of use of medications with mortality of COVID-­19 infection: a hospital-­based observational study Arthur W Wallace,1,2 Piera M Cirillo ‍ ‍,1,3 James C Ryan,1,4 Nickilou Y Krigbaum,1,3 Anusha Badathala,1 Barbara A Cohn1,3 To cite: Wallace AW, Cirillo PM, Ryan JC, et al. Association of the patterns of use of medications with mortality of COVID-­19 infection: a hospital-­based observational study. BMJ Open 2021;11:e050051. doi:10.1136/ bmjopen-2021-050051 ► Prepublication history for this paper is available online. To view these files, please visit the journal online (http://dx.doi.​ org/10.1136/bmjopen-2021-​ 050051). Received 09 February 2021 Accepted 03 December 2021 © Author(s) (or their employer(s)) 2021. Re-­use permitted under CC BY-­NC. No commercial re-­use. See rights and permissions. Published by BMJ. 1 San Franciso Veterans Affairs Medical Center, San Francisco, CA, USA 2 Department of Anesthesiology and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA 3 Child Health and Development Studies, Public Health Institute, Oakland, California, USA 4 Department of Gastroenterology, University of California, San Francisco, San Francisco, CA, USA Correspondence to Dr Arthur W Wallace; a​ rt.​wallace@v​ a.​gov ABSTRACT Objectives SARS-­CoV-­2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-­I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-­19 survival associated with ACE-­I, ARB and metformin use. Design This is a hospital-­based observational study of patients with COVID-­19 infection using logistic regression with correction for pre-­existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality. Setting Medical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-­19 infection, to classify patterns of ACE inhibitors (ACE-­I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality. Participants 9532 hospitalised patients with COVID-­19 infection followed for 60 days were analysed. Outcome measure Death from any cause within 60 days of COVID-­19 diagnosis was examined. Results Discontinuation of ACE-­I was associated with increased risk of death (OR: 1.4; 95% CI 1.2–1.7). Initiating (OR: 0.3; 95% CI 0.2–0.5) or continuous (OR: 0.6; 95% CI 0.5–0.7) ACE-­I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-­existing morbidity and propensity score adjustment. Conclusions Recent randomised clinical trials support the safety of continuing ACE-­I and ARB treatment in patients with COVID-­19 where indicated. Our study extends these findings to suggest a possible COVID-­19 survival benefit for continuing or initiating ACE-­I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-­I, ARBs and metformin.
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