Effectiveness of famotidine on the risk of poor prognosis in patients with COVID-19: A nationwide cohort study in Korea
Rosie Kwon, Hyung Jun Kim, Seung Won Lee, Ai Koyanagi, Jae Il Shin, Tae-Jin Song, Dong Keon Yon, Lee Smith
Heliyon, doi:10.1016/j.heliyon.2023.e16171
Famotidine has been proposed as a promising candidate for the treatment of coronavirus disease 2019 . However, there is limited research on the association of famotidine with the poor prognosis of COVID-19. Methods: The Korean nationwide cohort included 6,556 patients who tested positive on RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The poor COVID-19-related outcomes were defined on the basis of having encountered the composite outcome of high oxygen therapy, intensive care unit admission, administration of mechanical ventilation, or death. In addition, we performed exposure-driven propensity score matching for no H 2 -blocker use versus current famotidine use, and other H 2 -blocker use versus current famotidine use. Results: 4,785 (73.0%) patients did not use a H 2 -blocker, 393 (6.0%) patients were currently used famotidine, and 1,292 (19.7%) patients currently used H 2 -blocker other than famotidine. In multivariable analysis after matching (no H 2 -blocker use versus current famotidine use), there was no significant association between current famotidine use and composite outcomes (adjusted odd ratios [aOR]: 1.30, 95% confidence interval [CI]: 0.55-3.06). On the other hand, another matched cohort (other H 2 -blocker use versus current famotidine use), demonstrated a positive association between current famotidine use and composite outcomes (aOR: 3.56, 95% CI: 1. 03-12.28
Author contribution statement Rosie Kwon, Hyung Jun Kim,Seung Won Lee,: Performed the experiments; Analyzed and interpreted the data; Wrote the paper. Lee Smith, Ai Koyanagi: Contributed reagents, materials, analysis tools or data. Jae Il Shin, Tae-Jin Song, Dong Keon Yon: Conceived and designed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.
Table 3 Propensity-score-matching subgroup analyses for difference in length of stay at hospitalization according to famotidine use using analysis-ofcovariance model.
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2023.e16171.
References
References
Brennan, Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial, Gut,
doi:10.1136/gutjnl-2022-326952Chang, Woo, Park, Lee, Song, Improved oral hygiene care is associated with decreased risk of occurrence for atrial fibrillation and heart failure: a nationwide population-based cohort study, Eur. J. Prev. Cardiol,
doi:10.1177/2047487319886018Freedberg, Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: a propensity score matched retrospective cohort study, Gastroenterology,
doi:10.1053/j.gastro.2020.05.053Hogan Ii, Dual-histamine receptor blockade with cetirizine -famotidine reduces pulmonary symptoms in COVID-19 patients, Pulm. Pharmacol. Ther,
doi:10.1016/j.pupt.2020.101942Janowitz, Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series, Gut,
doi:10.1136/gutjnl-2020-321852Kim, Kim, Kim, Kim, Short and long-term mortality trends for cancer patients with septic shock stratified by cancer type from 2009 to 2017: a population-based cohort study, Cancers,
doi:10.3390/cancers13040657Kim, Yeniova, Global, regional, and national incidence and mortality of COVID-19 in 237 countries and territories, Life Cycle,
doi:10.54724/lc.2022.e10Kow, Abdul Sattar Burud, Hasan, Use of famotidine and risk of severe course of illness in patients with COVID-19: a meta-analysis, Mayo Clin. Proc,
doi:10.1016/j.mayocp.2021.03.001Kritas, Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy, J. Biol. Regul. Homeost. Agents,
doi:10.23812/20-Editorial-KritasKuno, So, Takahashi, Egorova, The association between famotidine and in-hospital mortality of patients with COVID-19, J. Med. Virol,
doi:10.1002/jmv.27375Kwon, National trends in physical activity among adolescents in South Korea before and during the COVID-19 pandemic, J. Med. Virol,
doi:10.1002/jmv.28456Kwon, None
Lee, Acharya, Propensity score matching for causal inference and reducing the confounding effects: statistical standard and guideline of Life Cycle Committee, Life Cycle,
doi:10.54724/lc.2022.e18Lee, Association between mental illness and COVID-19 susceptibility and clinical outcomes in South Korea: a nationwide cohort study, Lancet Psychiatr,
doi:10.1016/s2215-0366(20)30421-1Lee, Estimating COVID-19 infection and severity risks in patients with chronic rhinosinusitis: a Korean nationwide cohort study, J. Allergy Clin. Immunol,
doi:10.1016/j.jaip.2021.03.044Lee, Methods for testing statistical differences between groups in medical research: statistical standard and guideline of Life Cycle Committee,
doi:10.54724/lc.2022.e1Lee, Physical activity and the risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related mortality in South Korea: a nationwide cohort study, Br. J. Sports Med,
doi:10.1136/bjsports-2021-104203Lee, Proton pump inhibitors and the risk of severe COVID-19: a post-hoc analysis from the Korean nationwide cohort, Gut,
doi:10.1136/gutjnl-2020-323672Lee, Regression analysis for continuous independent variables in medical research: statistical standard and guideline of Life Cycle Committee, Life Cycle,
doi:10.54724/lc.2022.e3Lee, Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching, Gut,
doi:10.1136/gutjnl-2020-322248Ma, Patel, Vemparala, Krishnamurthy, Metformin is associated with favorable outcomes in patients with COVID-19 and type 2 diabetes mellitus, Sci. Rep,
doi:10.1038/s41598-022-09639-2Mukherjee, Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection, J. Biol. Chem,
doi:10.1016/j.jbc.2021.100925Mura, Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients, Signal Transduct. Targeted Ther,
doi:10.1038/s41392-021-00689-yPahwani, Efficacy of oral famotidine in patients hospitalized with severe acute respiratory syndrome coronavirus 2, Cureus,
doi:10.7759/cureus.22404Reis, Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: the TOGETHER randomized platform clinical trial, Lanc. Reg. Heal. Am,
doi:10.1016/j.lana.2021.100142Rommasi, Nasiri, Mirsaeidi, Immunomodulatory agents for COVID-19 treatment: possible mechanism of action and immunopathology features, Mol. Cell. Biochem,
doi:10.1007/s11010-021-04325-9Shoaibi, Fortin, Weinstein, Berlin, Ryan, Comparative effectiveness of famotidine in hospitalized COVID-19 patients, Am. J. Gastroenterol,
doi:10.14309/ajg.0000000000001153Son, Lim, Park, Trend of prevalence of atrial fibrillation and use of oral anticoagulation therapy in patients with atrial fibrillation in South Korea, J. Epidemiol,
doi:10.2188/jea.JE20160149Sun, Does famotidine reduce the risk of progression to severe disease, death, and intubation for COVID-19 patients? A systemic review and metaanalysis, Dig. Dis. Sci,
doi:10.1007/s10620-021-06872-zWen, Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19：a meta-analysis, Ann. Med,
doi:10.1080/07853890.2022.2034936Woo, Lee, Kim, Effect of pioglitazone in acute ischemic stroke patients with diabetes mellitus: a nested case-control study, Cardiovasc. Diabetol,
doi:10.1186/s12933-019-0874-5Wu, Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharm. Sin. B,
doi:10.1016/j.apsb.2020.02.008Xu, A meta-analysis on the risk factors adjusted association between cardiovascular disease and COVID-19 severity, BMC Publ. Health,
doi:10.1186/s12889-021-11051-wYeramaneni, Famotidine use is not associated with 30-day mortality: a coarsened exact match study in 7158 hospitalized patients with coronavirus disease 2019 from a large healthcare system, Gastroenterology,
doi:10.1053/j.gastro.2020.10.011Yoo, Marshall, Cho, Yoo, Lee, N-Nitrosodimethylamine-contaminated ranitidine and risk of cancer in South Korea: a nationwide cohort study, Life Cycle,
doi:10.54724/lc.2021.e1
