Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients

Abstract

INTRODUCTION: Famotidine has been posited as a potential treatment for coronavirus disease 2019 (COVID-19). We compared the incidence of COVID-19 outcomes (i.e., death and death or intensive services use) among hospitalized famotidine users vs proton pump inhibitors (PPIs) users, hydroxychloroquine users, or famotidine nonusers separately. METHODS: We constructed a retrospective cohort study using data from COVID-19 Premier Hospital electronic health records. The study population was COVID-19 hospitalized patients aged 18 years or older. Famotidine, PPI, and hydroxychloroquine exposure groups were defined as patients dispensed any medication containing 1 of the 3 drugs on the day of admission. The famotidine nonuser group was derived from the same source population with no history of exposure to any drug with famotidine as an active ingredient before or on the day of admission. Time at risk was defined based on the intention-to-treat principle starting 1 day after admission to 30 days after admission. For each study comparison group, we fit a propensity score model through large-scale regularized logistic regression. The outcome was modeled using a survival model. RESULTS: We identified 2,193 users of PPI, 5,950 users of the hydroxychloroquine, 1,816 users of famotidine, and 26,820 nonfamotidine users. After propensity score stratification, the hazard ratios (HRs) for death were as follows: famotidine vs no famotidine HR 1.03 (0.89–1.18), vs PPIs: HR 1.14 (0.94–1.39), and vs hydroxychloroquine: 1.03 (0.85–1.24). Similar results were observed for the risk of death or intensive services use. DISCUSSION: We found no evidence of a reduced risk of COVID-19 outcomes among hospitalized COVID-19 patients who used famotidine compared with those who did not or compared with PPI or hydroxychloroquine users.

Famotidine and Coronavirus Disease 2019

“…Our study and other retrospective studies of famotidine suggest there may be an association between the use of famotidine and improved outcomes among hospitalized patients with COVID-19 4,5 ; this was also suggested by a case series of famotidine with quantitative symptom tracking in nonhospitalized patients. 3 The data from Yeramaneni et al and other retrospective studies 6,7 show no association. We agree with Yeramaneni et al that famotidine should only be used as COVID-19 therapy in the context of a clinical trial.…”

Use of Famotidine and Risk of Severe Course of Illness in Patients With COVID-19

“…In the study by Yeramaneni et al, 3 the severe course of illness was defined as death within 30 days of hospitalization. In the study by Shoaibi et al, 4 the severe course of illness was defined as combined death and/or the requirement for mechanical ventilation, tracheostomy, or extracorporeal membrane oxygenation. In the study by Mather et al, 5 the severe course of illness was defined as a composite of death or requirement for ventilation.…”

“…Study characteristics are depicted in the Table. [3][4][5][6][7] All studies were retrospective and are deemed good quality with a Newcastle-Ottawa Scale ranging from 7 to 8 (Table ). The meta-analysis of 3 studies 4,5,7 (n¼31,563), which provided adjusted hazard ratio (aHR), revealed a nonsignificant association between the use of famotidine and the hazard for a severe course of illness in patients with COVID-19, relative to nonuse of famotidine (Figure; pooled HR¼0.83; 95% CI, 0.49 to 1.41).…”

No Evidence Indicates Famotidine Reduces the Risk of Serious Disease in COVID-19 Patients After Propensity Score Matching: Meta-Analysis and Systematic Reviews

“…2. duplicate. The last 4 articles were included [2 – 5] . The HR values of Propensity Score Matching from 4 articles were extracted, the patient's serve disease or death or intubation data of famotidine and non-famotidine were converted into the corresponding log (RR) and SE (considering the low mortality of COVID19, it can be considered that the HR value is equivalent to the OR value) (Table 1 ).…”

“…However, Mather et al believed that the matching of propensity scores to adjust for age differences between famotidine and non-famotidine patients did not change the significance of the differences in mortality or combined mortality and intubation in the analysis [4] . Similarly, Shoaibi et al stated that with real-world data from a large multi-agency hospital database, no evidence has been found that famotidine used in hospitalized COVID-19 patients reduced the risk of death compared with non-users [5] . To better understand these contradictions, we analyzed the data of these articles through meta-analysis.…”