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Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients

Fung et al., PLoS ONE, doi:10.1371/journal.pone.0266922 (date from preprint)
Oct 2021  
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Mortality 0% Improvement Relative Risk Hospitalization 6% Case -12% Famotidine for COVID-19  Fung et al.  Prophylaxis Is prophylaxis with famotidine beneficial for COVID-19? Retrospective study in the USA Lower hospitalization (p=0.00016) and more cases (p<0.0001) c19early.org Fung et al., PLoS ONE, October 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.
5,300+ studies for 116 treatments. c19early.org
Retrospective database analysis of 374,229 patients in the USA, showing higher cases, lower hospitalizations, and no change in mortality with famotidine use.
Standard of Care (SOC): SOC for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments1. Only expensive, high-profit treatments were approved. Low-cost treatments were excluded, reducing the probability of treatment—especially early—due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
This study is excluded in the after exclusion results of meta analysis: not fully adjusting for the different baseline risk of systemic autoimmune patients.
Study covers HCQ and famotidine.
risk of death, no change, HR 1.00, p = 1.00, vs. never used.
risk of hospitalization, 6.0% lower, HR 0.94, p < 0.001, vs. never used.
risk of case, 12.0% higher, HR 1.12, p < 0.001, vs. never used.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Fung et al., 1 Oct 2021, retrospective, population-based cohort, USA, peer-reviewed, 6 authors.
This PaperFamotidineAll
Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients
Kin Wah Fung, Seo H Baik, Fitsum Baye, Zhaonian Zheng, Vojtech Huser, Clement J Mcdonald
PLOS ONE, doi:10.1371/journal.pone.0266922
Background Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. Methods Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dualeligibility status, and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), statins, warfarin, direct factor Xa inhibitors, P2Y12 inhibitors, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator, and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. Results Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 278,912 (74.6%) were on at least one study drug. The three most common study drugs among COVID-19 patients were statins 187,374 (50.1%), ACEI 97,843 (26.2%) and ARB 83,290 (22.3%). For all three outcomes (diagnosis, hospitalization and death), current users of ACEI, ARB,
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DOI record: { "DOI": "10.1371/journal.pone.0266922", "ISSN": [ "1932-6203" ], "URL": "http://dx.doi.org/10.1371/journal.pone.0266922", "abstract": "<jats:sec id=\"sec001\">\n<jats:title>Background</jats:title>\n<jats:p>Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods</jats:title>\n<jats:p>Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dual-eligibility status, and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), statins, warfarin, direct factor Xa inhibitors, P2Y12 inhibitors, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator, and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results</jats:title>\n<jats:p>Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 278,912 (74.6%) were on at least one study drug. The three most common study drugs among COVID-19 patients were statins 187,374 (50.1%), ACEI 97,843 (26.2%) and ARB 83,290 (22.3%). For all three outcomes (diagnosis, hospitalization and death), current users of ACEI, ARB, statins, warfarin, direct factor Xa inhibitors and P2Y12 inhibitors were associated with reduced risks, compared to never users. Famotidine did not show consistent significant effects. Hydroxychloroquine did not show significant effects after censoring of recent starters.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion</jats:title>\n<jats:p>Maintenance use of ACEI, ARB, warfarin, statins, direct factor Xa inhibitors and P2Y12 inhibitors was associated with reduction in risk of acquiring COVID-19 and dying from it.</jats:p>\n</jats:sec>", "author": [ { "ORCID": "http://orcid.org/0000-0003-0593-5377", "affiliation": [], "authenticated-orcid": true, "family": "Fung", "given": "Kin Wah", "sequence": "first" }, { "affiliation": [], "family": "Baik", "given": "Seo H.", "sequence": "additional" }, { "affiliation": [], "family": "Baye", "given": "Fitsum", "sequence": "additional" }, { "affiliation": [], "family": "Zheng", "given": "Zhaonian", "sequence": "additional" }, { "affiliation": [], "family": "Huser", "given": "Vojtech", "sequence": "additional" }, { "affiliation": [], "family": "McDonald", "given": "Clement J.", "sequence": "additional" } ], "container-title": "PLOS ONE", "container-title-short": "PLoS ONE", "content-domain": { "crossmark-restriction": false, "domain": [ "www.plosone.org" ] }, "created": { "date-parts": [ [ 2022, 4, 18 ] ], "date-time": "2022-04-18T17:27:56Z", "timestamp": 1650302876000 }, "deposited": { "date-parts": [ [ 2022, 4, 18 ] ], "date-time": "2022-04-18T17:28:41Z", "timestamp": 1650302921000 }, "editor": [ { "affiliation": [], "family": "Mogi", "given": "Masaki", "sequence": "first" } ], "funder": [ { "DOI": "10.13039/100000092", "award": [ "Intramural research program" ], "doi-asserted-by": "publisher", "name": "U.S. National Library of Medicine" } ], "indexed": { "date-parts": [ [ 2023, 10, 4 ] ], "date-time": "2023-10-04T10:32:07Z", "timestamp": 1696415527413 }, "is-referenced-by-count": 7, "issue": "4", "issued": { "date-parts": [ [ 2022, 4, 18 ] ] }, "journal-issue": { "issue": "4", "published-online": { "date-parts": [ [ 2022, 4, 18 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/publicdomain/zero/1.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 4, 18 ] ], "date-time": "2022-04-18T00:00:00Z", "timestamp": 1650240000000 } } ], "link": [ { "URL": "https://dx.plos.org/10.1371/journal.pone.0266922", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "340", "original-title": [], "page": "e0266922", "prefix": "10.1371", "published": { "date-parts": [ [ 2022, 4, 18 ] ] }, "published-online": { "date-parts": [ [ 2022, 4, 18 ] ] }, "publisher": "Public Library of Science (PLoS)", "reference": [ { "DOI": "10.1161/CIRCULATIONAHA.104.510461", "article-title": "Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2", "author": "C.M. 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