People exposed to proton‐pump inhibitors shortly preceding COVID‐19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: A nationwide matched cohort study

  1. Ivan Kodvanj
  2. Jan Homolak
  3. Vladimir Trkulja

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

To assess whether exposure to proton‐pump inhibitors (PPIs) shortly preceding COVID‐19 diagnosis affected the risk of subsequent hospitalizations and mortality.

Methods

This population‐based study embraced first COVID‐19 episodes in adults diagnosed up to 15 August 2021 in Croatia. Patients were classified based on exposure to PPIs and burden of PPI‐requiring morbidities as nonusers (no issued prescriptions, no recorded treatment‐requiring conditions between 1 January 2019 and COVID‐19 diagnosis), possible users (no issued prescriptions, but morbidities present; self‐medication possible) and users (≥1 prescription within 3 months prior to the COVID‐19 diagnosis; morbidities present). Subsets were mutually exactly matched for pre‐COVID‐19 characteristics. The contrast between users and possible users informed about the effect of PPIs that is separate of the effect of PPI‐requiring conditions.

Results

Among 433 609 patients, users and possible users were matched 41 195 (of 55 098) to 17 334 (of 18 170) in the primary and 33 272 to 16 434 in the sensitivity analysis. There was no relevant difference between them regarding mortality (primary: relative risk [RR] = 0.93 [95% confidence interval 0.85–1.02; absolute risk difference [RD] = −0.34% [−0.73, 0.03]; sensitivity: RR = 0.88 [0.78–0.98]; RD = −0.45% [−0.80, −0.11]) or hospitalizations (primary: RR = 1.04 [0.97–1.13]; RD = 0.29% [−0.16, 0.73]; sensitivity: RR = 1.05 [0.97–1.15]; RD = 0.32% [−0.12, 0.75]). The risks of both were slightly higher in possible users or users than in nonusers (absolutely by ~0.4–1.6%) indicating the effect of PPI‐requiring morbidities.

Conclusion

Premorbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID‐19 patients, but PPI‐requiring morbidities seemingly slightly increase the risk of both.

Article activity feed

  1. Version published to 10.1111/bcp.15525
  2. Version published to 10.1101/2022.04.30.22274526v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.04.30.22274526: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Linked were data on: date and mode of COVID-19 diagnosis; demographics and COVID-19 vaccination status at diagnosis; medical histories throughout 2019 up to October 31 2021, including information on comorbidities (with International Classification of Diseases [ICD-10] codes), all issued prescriptions (with Anatomical Therapeutic Chemical codes, ATC) and other medical care, hospital admissions and diagnoses and dates and causes of death.
    ATC
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The present analysis suffers from several potential limitations. First, it used a database generated for this particular purpose using routinely collected administrative data, and not a dedicated prospectively planned database. It was re-checked systematically and (Figure 1) only 0.47% of the originally included entries had erroneous/missing data on key variables like COVID-19 diagnosis and dates, age, vaccination status. Also, we allowed for a long-enough follow-up for outcomes to occur in all COVID-19-diagnosed subjects, and all issued prescriptions (for PPIs or any other) or individual subject ICD-10 codes were automatically included into the national Central Health Information System. Still, one cannot completely exclude a possibility of minor inaccuracies – e.g., that some ICD-10 code should have been - and was not - entered into the system for a particular individual. We believe, however, that the risk of such inaccuracies was minimized by the fact that we left a period of a minimum one year + 2 months (data date back to January 1 2019; first COVID-19 case in February 2020) before COVID-19 diagnosis for comorbidities to be registered, and no relevant comorbidity was likely to be missed. Next, as it is common in pharmacoepiedmiology, exposure (to PPIs) is defined based on issued prescriptions without a direct insight into actual consumption (compliance). This is an unavoidable fact and a potential source of bias. In the present setting, however, this might be of a limite...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2022.04.30.22274526v1 on medRxiv