Effects of gastric acid suppression drugs on COVID-19 outcomes still unclear

A meta-analysis didn't find an association between famotidine use and severe disease or death from COVID-19, and the association of these outcomes with proton-pump inhibitors varied by study type.

Famotidine didn't improve COVID-19 outcomes and data on proton-pump inhibitors (PPIs) were mixed in a recent meta-analysis.

The analysis included nine retrospective observational studies that evaluated associations between famotidine or PPI use and outcomes in patients with COVID-19 and reported summary results as an adjusted odds ratio (OR) or hazard ratio (HR). A total of 21,285 patients were included. The results were published as a short survey by Gastroenterology on Feb. 17.

An unadjusted analysis found no association between famotidine use and COVID-19 disease severity (relative risk, 1.02; 95% CI, 0.58 to 1.81) or COVID-19 mortality (OR, 0.79; 95% CI, 0.19 to 3.32). Similarly, an unadjusted analysis didn't show a significant association between PPI use and disease severity (relative risk, 1.95; 95% CI, 0.94 to 4.07). However, combining four studies that reported data as adjusted ORs indicated that PPI use was associated with an increased risk of severe disease (adjusted OR, 1.79; 95% CI, 1.25 to 2.57). Analysis of the two studies that used HRs showed no significant effect (pooled HR, 1.84; 95% CI, 0.95 to 3.59). PPI use was associated with increased risk of mortality (pooled OR, 2.12; 95% CI, 1.29 to 3.51).

The authors noted some previous research had suggested that famotidine might be associated with improved outcomes in COVID-19 and that PPI use might be associated with increased risk of severe disease and death. “There is no clear mechanism to explain why PPIs might be associated with worse outcomes in COVID-19 patients. However, suppression of gastric acid by PPIs increases intragastric pH and may result in impaired ability to destroy ingested pathogens,” the authors wrote.

They recommended that clinicians follow Infectious Diseases Society of America guidelines and the evidence and not administer famotidine to patients with COVID-19 outside of a randomized controlled trial. “Similarly, there is no compelling evidence to withhold or withdraw PPI treatment from a patient with COVID-19 who has a valid indication for it,” the authors said.

The meta-analysis had several limitations, including that all of the included studies were observational and retrospective in nature, with the attendant risks of measured and unmeasured confounding. “Because of these limitations, definite conclusions cannot be made based on the results of this meta-analysis,” the authors said. They added that although randomized controlled trials of PPIs in COVID-19 are not feasible, there should be multicenter prospective studies that adjust for confounders and avoid biases such as immortal time bias.