Concerns have been raised regarding proton pump inhibitor (PPI) use and risk of severe coronavirus disease 2019 (COVID-19). Observational studies have yielded heterogeneous results and were subject to important methodological limitations. To examine the association between the receipt of PPIs and risk of COVID-19 hospitalizations and severe in-hospital outcomes or death. Case-control study among Medicare fee-for-service beneficiaries 66+ years old with gastroesophageal reflux disorder (GERD). Within this population, we identified cases by an incident hospital discharge diagnosis of COVID-19 from April 1 to December 11, 2020, using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) U07.1, and randomly selected up to 10 controls per case, matched on date and neighborhood. We defined PPI use as a prescription providing ≥15 days of supply in the 30 days before admission, with H2-receptor antagonist (H2RA) use as the reference to account for indication. We analyzed uncomplicated hospitalizations and hospitalizations with severe outcomes (intensive/coronary care unit admission, invasive mechanical ventilation, or death), estimating odds ratios (ORs), and 95% confidence intervals (CIs) with multinomial conditional logistic regression adjusted for demographics, comorbidities, chronic medications, and health care utilization. We matched 25,867 uncomplicated and 12,954 severe hospitalized COVID-19 cases to 146,972 and 73,104 controls, respectively. Cases tended to be older and have more comorbidities. Relative to H2RA use, we found no association of PPI use with uncomplicated COVID-19 hospitalization (OR 0.99, 95% CI 0.93-1.06) or severe COVID-19 hospitalization (OR 1.00, 95% CI 0.91-1.10). Relative to H2RA use, PPI use was not associated with uncomplicated or severe COVID-19 hospitalizations among Medicare beneficiaries with GERD.
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