Use of proton pump inhibitors and risk of severe COVID-19: A case-control study in United States Medicare beneficiaries

Pharmacotherapy. 2024 Oct;44(10):803-810. doi: 10.1002/phar.4614. Epub 2024 Oct 18.

Abstract

Background: 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.

Aims: To examine the association between the receipt of PPIs and risk of COVID-19 hospitalizations and severe in-hospital outcomes or death.

Methods: 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.

Results: 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).

Conclusions: Relative to H2RA use, PPI use was not associated with uncomplicated or severe COVID-19 hospitalizations among Medicare beneficiaries with GERD.

Keywords: COVID‐19; GERD; H2RA; PPI.

MeSH terms

  • Aged
  • Aged, 80 and over
  • COVID-19* / epidemiology
  • Case-Control Studies
  • Female
  • Gastroesophageal Reflux* / drug therapy
  • Gastroesophageal Reflux* / epidemiology
  • Histamine H2 Antagonists / therapeutic use
  • Hospitalization* / statistics & numerical data
  • Humans
  • Male
  • Medicare* / statistics & numerical data
  • Proton Pump Inhibitors* / adverse effects
  • SARS-CoV-2
  • Severity of Illness Index
  • United States / epidemiology

Substances

  • Proton Pump Inhibitors
  • Histamine H2 Antagonists