Renin-Angiotensin-Aldosterone-System inhibitor use in patients with COVID-19 infection and prevention of serious events: a cohort study in commercially insured patients in the US

  1. Maria C Schneeweiss
  2. Sandra Leonard
  3. Andrew Weckstein
  4. Sebastian Schneeweiss
  5. Jeremy A Rassen

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Abstract

Objectives

There is lack of clarity regarding the role of angiotensin receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEi) in interfering with the SARS-COV-2 binding on human cells and the resulting change in disease severity. We sought to assess the risk of hospitalization for COVID-19 and serious complications in current users of ARB or ACEi compared to users of dihydropyridine calcium channel blockers (dhpCCB).

Design

Cohort study

Setting

The analysis used de-identified, patient level data from HealthVerity, linking longitudinal data from US medical and pharmacy claims, which contain information on inpatient or outpatient diagnoses, procedures and medication dispensing.

Participants

We identified patients aged 40+ and free of chronic kidney disease (CKD) who were newly diagnosed COVID-19, between March 1, 2020 and May 30, 2020, and adherent to ACEi, ARB, or dhpCCB therapy.

Interventions

Current use of an ACEi, ARB, or dhpCCB.

Main outcome measures

We compared the 30-day risk of hospitalization for COVID-19 and serious complications.

Results

Of 24,708 patients identified, 7,571 were current users of an ARB, 8,484 of an ACEi, and 8,653 of a dhpCCB. The unadjusted 30-day risk of hospitalization for COVID-19 was 2.66% among ARB users, and 2.90% among ACEi users and 3.68% in dhpCCB users. In the PS-matched cohort, the risk of hospitalization among ARB users was 17% lower as compared to dhpCCB (RR=0.83; 0.68-1.00), and the risk among ACE users was 10% lower as compared to dhpCCB (RR=0.90; 0.76-1.07). When including patients with pre-existing CKD, the protective effect of ARB (RR= 0.74; 0.62-0.88) and ACEi (RR=0.84; 0.71-0.99) was more pronounced.

Conclusions

This cohort study showed that neither ARB nor ACEi use increase the risk of severe COVID-19 disease among those infected, and instead suggests that current use of ARB may offer a protective effect. This study found no evidence to support the discontinuation of ARB/ACEi therapy.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.22.20159855: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationAll analyses were conducted using the Aetion Evidence Platform v3.19 (including R version 4.0.2), which has been validated and has successfully predicted randomized control trial findings.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    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.

  2. Version published to 10.1101/2020.07.22.20159855v1 on medRxiv