Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study
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
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.
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Wallace et al., 31 Dec 2021, retrospective, database analysis, USA, peer-reviewed, 6 authors.
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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is 100% available and effective for all current and future variants. We do not
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