Background: Concerns have been raised regarding proton pump inhibitor (PPI) use and risk of severe Covid-19. Observational studies to date have shown inconsistent findings and have been subject to methodologic limitations.
Objectives: To examine the association between use of PPIs and severe outcomes of Covid-19.
Methods: We conducted a case-control study among Medicare beneficiaries 66+ years old, diagnosed with uncomplicated gastroesophageal reflux disorder (GERD) and enrolled in Medicare Parts A (hospitalization), B (office-based care), and D (prescription drug coverage). We identified all cohort members with an incident ICD-10-CM hospital discharge diagnosis of Covid-19 from April 1 to December 11, 2020, with their date of admission as index date. We randomly selected from the cohort of GERD patients up to 10 controls per case, matching on index date and, to address disease risk and unmeasured socioeconomic factors, also neighborhood (census block or block group). We defined PPI use as a prescription providing ≥ 15 days of supply in the 30 days prior to index date. Use of an H2-receptor antagonist (H2RA), similarly defined, was the comparator. We divided Covid-19 hospitalizations into 2 severity levels: uncomplicated and severe (including intensive care unit admission, invasive mechanical ventilation or death). We adjusted for demographics, comorbidities, chronic medications, and healthcare utilization, and estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable multinomial conditional logistic regression.
Results: We identified 25,867 uncomplicated and 12,954 severe hospitalized Covid-19 cases, matching them to 146,972 and 73,104 controls, respectively. Cases tended to be older and have more chronic medical conditions. Relative to H2RA use, there was no association of PPI use with uncomplicated Covid-19 hospitalization (odds ratio (OR) 0.99, 95% CI 0.93-1.06), or severe Covid-19 hospitalization (OR 1.00, 95% CI 0.91-1.10). Secondary comparisons to nonusers for PPIs and H2RAs showed a modest association for PPI use, with ORs of 1.10 (95% CI 1.07, 1.14) for uncomplicated hospitalization and 1.12 (95% CI 1.07, 1.17) for severe hospital outcomes; corresponding ORs for H2RA users versus nonusers were 1.11 (95% CI 1.04-1.19) and 1.12 (95% CI 1.02-1.24), respectively.
Conclusions: Relative to use of H2RAs, PPI use was not associated with uncomplicated or severe Covid-19 hospitalization among Medicare beneficiaries with GERD. A small risk for Covid-19 hospitalization with either PPI or H2RA use versus nonuse may reflect residual confounding by indication.
