Famotidine use within 24 hours of admission does not improve but may worsen 30-day mortality of patients hospitalized with COVID-19, according to a retrospective study. At least two previous studies have reported an association between in-hospital famotidine use and reduced risk of death or intubation in patients with COVID-19. Dr. Gregg Fromell and colleagues from HCA Healthcare, in Nashville, Tennessee, evaluated the effect of famotidine on 30-day all-cause mortality among adults admitted to affiliated hospitals who tested positive for SARS-CoV-2 RNA. Among a total of 7,158 patients, 15.7% were exposed to famotidine and 84.3% were not. In a subgroup of 1,156 patients chosen by Coarsened Exact Matching (CEM) of age, sex, race, ethnicity, BMI, comorbidities and in-hospital hydroxychloroquine use, 35.5% were exposed and 64.5% were unexposed to famotidine. All-cause mortality at 30 days was 9.6% in the overall sample and 11.5% in the CEM subgroup. Famotidine users had significantly higher 30-day mortality than nonusers in both the pre-match group (18.2% vs. 8.0%, respectively) and the CEM subgroup (15.1% vs. 9.5%, respectively), the researchers report in Gastroenterology. After adjustment for World Health Organization (WHO) severity, smoking status and listed medications, there was no significant association between in-hospital famotidine use and 30-day mortality within the CEM group. In a secondary analysis, patients not using famotidine at home but receiving famotidine in the hospital had a significant 77% increase in their odds of 30-day mortality. "Our study findings do not support the evidence of in-hospital famotidine use on reduced risk of mortality in COVID-19 patients," the authors conclude. "Investigation of off-label use of low-cost, better tolerated, and widely available drugs in COVID-19 patients is warranted." "Until safety and efficacy of these drugs are established by randomized controlled trials, results from these observational studies should be interpreted with caution," they add. Dr. Daniel E. Freedberg of Columbia University Mailman School of Public Health, in New York City, who has also studied the impact of famotidine on COVID-19 mortality, told Reuters Health by email, "This study contradicts our retrospective study, which found that famotidine was associated with decreased risk for death among hospitalized patients with COVID-19. It's surprising that two studies with such similar designs had opposite results. It's possible that institutional differences related to patterns of famotidine use (i.e., which types of patients were given famotidine) underlie the differences in study findings." "Famotidine should only be used for COVID-19 in the context of a clinical trial," he said. "That was true before this study was published, and it remains true." "A randomized controlled trial of famotidine for COVID-19 is underway," Dr. Freedberg said. "The results of that trial are going to be the crucial next step in determining the future of famotidine for COVID-19." Dr. Wai Keung Leung of Queen Mary Hospital, in Hong Kong, who has also studied famotidine in the setting of COVID-19, told Reuters Health by email, "Overall, the results are not unexpected and are similar to our previous findings from Hong Kong that famotidine use is not associated with better outcome in patients with COVID-19." "The current study showed that those who did not use famotidine at home but were given famotidine in hospital had a higher risk of 30-day mortality," he said. "This, however, should be interpreted with caution as this could be confounded by indication bias, as patients who were given famotidine in this cohort were older, with higher WHO severity and comorbidities, which were all risk factors for mortality." "Given the retrospective nature of these published studies with conflicting results, a prospective randomized study is needed to resolve these controversies," Dr. Leung said. "Meanwhile, famotidine should be used judiciously in patients with COVID-19." Dr. Vijay P. Singh of Mayo Clinic Arizona, in Scottsdale, who coauthored an editorial related to Dr. Freedberg's study, told Reuters Health by email that in the new study, "patients given famotidine had higher comorbidities and a higher proportion of severe patients at admission. They also received more remdesivir and tocilizumab. So it is likely that their higher severity led to the use of these therapies, including famotidine. Conversely, it is very unlikely that famotidine made the disease severe." "Therefore," he said, "its use when indicated (e.g., heartburn) should be appropriate, unless specifically contraindicated (e.g., allergy)." Dr. Fromell did not respond to a request for comments. —Will Boggs MD Source
