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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
Dec 2021  
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Mortality -11% Improvement Relative Risk Famotidine for COVID-19  Wallace et al.  Prophylaxis Is prophylaxis with famotidine beneficial for COVID-19? Retrospective 7,944 patients in the USA No significant difference in mortality Wallace et al., BMJ Open, December 2021 Favorsfamotidine Favorscontrol 0 0.5 1 1.5 2+
Famotidine for COVID-19
26th treatment shown to reduce risk in October 2021
*, now with p = 0.00028 from 30 studies, recognized in 2 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments.
Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing no significant difference in mortality with famotidine 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.
Study covers metformin and famotidine.
risk of death, 11.0% higher, RR 1.11, p = 0.33, treatment 98 of 423 (23.2%), control 1,436 of 7,521 (19.1%), adjusted per study, odds ratio converted to relative risk, multivariable.
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.
This PaperFamotidineAll
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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.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>9532 ' 'hospitalised patients with COVID-19 infection followed for 60 days were ' 'analysed.</jats:p></jats:sec><jats:sec><jats:title>Outcome measure</jats:title><jats:p>Death ' 'from any cause within 60 days of COVID-19 diagnosis was ' 'examined.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>', 'DOI': '10.1136/bmjopen-2021-050051', 'type': 'journal-article', 'created': { 'date-parts': [[2021, 12, 31]], 'date-time': '2021-12-31T15:30:28Z', 'timestamp': 1640964628000}, 'page': 'e050051', 'update-policy': '', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': [ 'Association of the patterns of use of medications with mortality of COVID-19 infection: a ' 'hospital-based observational study'], 'prefix': '10.1136', 'volume': '11', 'author': [ {'given': 'Arthur W', 'family': 'Wallace', 'sequence': 'first', 'affiliation': []}, { 'ORCID': '', 'authenticated-orcid': False, 'given': 'Piera M', 'family': 'Cirillo', 'sequence': 'additional', 'affiliation': []}, {'given': 'James C', 'family': 'Ryan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nickilou Y', 'family': 'Krigbaum', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anusha', 'family': 'Badathala', 'sequence': 'additional', 'affiliation': []}, {'given': 'Barbara A', 'family': 'Cohn', 'sequence': 'additional', 'affiliation': []}], 'member': '239', 'published-online': {'date-parts': [[2021, 12, 31]]}, 'reference': [ { 'key': '2021123107251020000_11.12.e050051.1', 'doi-asserted-by': 'crossref', 'first-page': '91', 'DOI': '10.1016/j.jare.2020.03.005', 'article-title': 'COVID-19 infection: origin, transmission, and characteristics of human ' 'coronaviruses', 'volume': '24', 'author': 'Shereen', 'year': '2020', 'journal-title': 'J Adv Res'}, { 'key': '2021123107251020000_11.12.e050051.2', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/path.1570'}, { 'key': '2021123107251020000_11.12.e050051.3', 'first-page': '39', 'article-title': 'Short-term dexamethasone in Sars-CoV-2 patients', 'volume': '103', 'author': 'Selvaraj', 'year': '2020', 'journal-title': 'R I Med J'}, { 'key': '2021123107251020000_11.12.e050051.4', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NE-JMoa2007016'}, { 'key': '2021123107251020000_11.12.e050051.5', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/gutjnl-2020-321852'}, { 'key': '2021123107251020000_11.12.e050051.6', 'doi-asserted-by': 'crossref', 'unstructured': 'Sen Gupta PS , Biswal S , Singha D . 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