People exposed to proton pump inhibitors shortly preceding COVID-19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: a nation-wide matched cohort study

Abstract

BackgroundSeveral studies assessed the effect of pre-morbid exposure to proton pump inhibitors (PPIs) on disease course in adult COVID-19 patients with somewhat inconsistent results.MethodsThis population-based matched cohort study embraced first COVID-19 episodes in adults diagnosed up to August 15 2021 in Croatia. Considering over-the-counter (OTC) availability of PPIs, patients were classified based on exposure to PPIs and burden of PPI-requiring conditions as “non-users” (no issued prescriptions, no recorded treatment-requiring conditions between January 1 2019 and COVID-19 diagnosis), “possible users” (no issued prescriptions, recorded treatment-requiring conditions; OTC use possible) and “users” (different intensity of issued prescriptions over 12 months prior to diagnosis, at least one within 3 months). Subsets were mutually exactly matched in respect to a range of pre-COVID-19 characteristics. The contrast between “users” and “possible users” was considered the most informative for the effect of PPIs that is separate of the effect of PPI-requiring conditions.ResultsAmong 433609 COVID-19 patients, 332389 were PPI “non-users”, 18170 were “possible users”, and 55098 were “users”. Users and possible users were matched 41195 to 17334 and 33272 to 16434 in the primary and sensitivity analyses. There was no relevant difference between “users” and “possible users” regarding COVID-19-related mortality [RR=0.93 (95%CI 0.85-1.02; RD= -0.34% (−0.73, 0.03) in primary and RR=0.88 (0.78-0.98); RD=-0.45 (− 0.80, -0.11) in sensitivity analysis] or COVID-19-related hospitalizations [RR=1.04 (0.97-1.13); RD=0.29% (−0.16, 0.73) in primary and RR=1.05 (0.97-1.15); RD=0.32% (−0.12, 0.75) in sensitivity analysis].ConclusionsPre-morbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID-19 patients.