Famotidine does not decrease risk for mortality in COVID-19
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Results from a recent study did not demonstrate a correlation between in-hospital famotidine use and a reduced risk for mortality in COVID-19 patients.
“Until safety and efficacy of these drugs are established by randomized controlled trials, results from these observational studies should be interpreted with caution,” Samrat Yeramaneni, MBBS, PhD, from the Sarah Cannon Research Institute, HCA Healthcare in Nashville, and colleagues wrote.
Yeramaneni and colleagues identified 7,158 patients who tested positive for SARS-CoV-2. Thirty-day all-cause mortality served as the primary outcome. In-hospital famotidine use, regardless of dose or route, within 24 hours of hospital admission served as primary exposure. A Coarsened Exact Matching technique was used to mitigate bias from non-randomized treatment assignment among famotidine users and non-users on age, sex, race, ethnicity, BMI, comorbidities and in-hospital hydroxychloroquine use.
Additionally, the association between famotidine use and 30-day mortality was assessed with a multivariable logistic regression model.
Investigators reported exposure among 1,127 of 7,158 patients in the pre-match cohort. Results from CEM showed exposure among 410 of 1,156 patients.
According to researchers, patients received famotidine for a median 6 days and a median cumulative dose of 160 mg.
“Famotidine users were on average 6 years older (P < .0001), with higher admission WHO severity (P < .0001), higher proportions of comorbid conditions (all P < .001), more likely to receive [hydroxychloroquine, acetazolamide], ACE-I, [angiotensin II receptor blockers], antibiotics, antivirals, remdesivir, tocilizumab and steroids (all P < .001),” the investigators wrote.
Results showed 687 patients in the pre-match cohort and 113 in the post-match cohort died within 30-days of admission.
“Pre-match 30-day mortality was 18.2% famotidine users vs. 8% non-famotidine users (P < .0001). Post-match 30-day mortality was 15.1% famotidine users vs. 9.5% non-famotidine users (P = .007),” Yeramaneni and colleagues wrote.
Multivariable logistic regression results showed no correlation between in-hospital famotidine use and 30-day mortality (aOR = 1.59; 95% CI, 0.94-2.71) after adjusting for WHO severity, smoking status and listed medications.
“Secondary analysis, accounting for interaction between in-hospital and at-home famotidine use showed that patients not using famotidine at-home, but receiving famotidine in the hospital, were at higher risk of 30-day mortality (aOR = 1.77; 95% CI, 1.03-3.03),” they wrote.
Perspective
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Sara El Ouali, MD
Given the lack of treatment options for COVID-19, drug repurposing is being pursued to find potential therapies. Famotidine, a histamine-2 receptor antagonist, was identified as a potential COVID-19 treatment after computational techniques showed it could inhibit a SARS-CoV-2 protease. Researchers have looked at its impact on COVID-19 outcomes, but data have been inconsistent.
A retrospective study in Hong Kong showed no association between COVID-19 outcomes and the use of famotidine. However, two U.S. retrospective studies, using propensity score matching, showed famotidine was associated with a decreased risk for death or intubation in hospitalized patients.
The study presented here attempted to further clarify the impact of famotidine use in COVID-19. In this larger retrospective study, investigators used coarsened exact matching to reduce the risk for bias and found a higher 30-day mortality in the matched cohort among famotidine users compared with non-users. However, after adjusting for confounders, there was no correlation between in-hospital famotidine use and mortality.
A secondary analysis showed patients using in-hospital famotidine had a higher risk for 30-day mortality while at-home famotidine users did not, which may be related to the fact that patients starting famotidine in-hospital tend to be sicker. However, although researchers adjusted for several confounders, there could remain unmeasured confounders.
Until further data are available, specific recommendations regarding famotidine use in COVID-19 cannot be made. Several randomized controlled trials are underway in the U.S. and should soon help us better understand the true impact of famotidine in COVID-19.
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