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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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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.

Lower risk for mortality, hospitalization, recovery, and viral clearance.

No treatment is 100% effective. Protocols combine treatments. ^* >10% efficacy, ≥3 studies.

4,900+ studies for 102 treatments. c19early.org

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.

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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 Paper Famotidine All

{ 'indexed': {'date-parts': [[2022, 1, 1]], 'date-time': '2022-01-01T05:55:33Z', 'timestamp': 1641016533940}, 'reference-count': 33, 'publisher': 'BMJ', 'issue': '12', 'license': [ { 'start': { 'date-parts': [[2021, 12, 30]], 'date-time': '2021-12-30T00:00:00Z', 'timestamp': 1640822400000}, 'content-version': 'unspecified', 'delay-in-days': 29, 'URL': 'http://creativecommons.org/licenses/by-nc/4.0/'}], 'funder': [ {'name': 'Mercatus Center, George Mason University Fast Grants', 'award': ['#2207']}, { 'name': 'UC Office of the President, Emergency COVID-19 Research Seed Funding', 'award': ['R00RG3118']}, {'name': 'Mercatus Center, George Mason University Fast Grants', 'award': ['#2005']}], 'content-domain': {'domain': ['bmj.com'], 'crossmark-restriction': True}, 'short-container-title': ['BMJ Open'], 'published-print': {'date-parts': [[2021, 12]]}, 'abstract': 'ObjectivesSARS-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.DesignThis 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.SettingMedical ' '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.Participants9532 ' 'hospitalised patients with COVID-19 infection followed for 60 days were ' 'analysed.Outcome measureDeath ' 'from any cause within 60 days of COVID-19 diagnosis was ' 'examined.ResultsDiscontinuation ' '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.ConclusionsRecent ' '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.', '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': 'http://dx.doi.org/10.1136/crossmarkpolicy', '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': 'http://orcid.org/0000-0003-4571-4544', '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 . Binding insight of clinically ' 'oriented drug famotidine with the identified potential target of ' 'SARS-CoV-2. J Biomol Struct Dyn 2020:1–7.', 'DOI': '10.26434/chemrxiv.12382265'}, { 'key': '2021123107251020000_11.12.e050051.7', 'doi-asserted-by': 'publisher', 'DOI': '10.1053/j.gastro.2020.05.053'}, { 'key': '2021123107251020000_11.12.e050051.8', 'doi-asserted-by': 'crossref', 'unstructured': 'Magagnoli J , Narendran S , Pereira F . Outcomes of hydroxychloroquine ' 'usage in United States veterans hospitalized with Covid-19. medRxiv ' '2020;2020.04.16.20065920.', 'DOI': '10.1101/2020.04.16.20065920'}, { 'key': '2021123107251020000_11.12.e050051.9', 'doi-asserted-by': 'crossref', 'unstructured': 'Cao YC , Deng QX , Dai SX . Remdesivir for severe acute respiratory ' 'syndrome coronavirus 2 causing COVID-19: an evaluation of the evidence. 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