Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19

  1. Emilia Roy-Vallejo
  2. Aquilino Sánchez Purificación
  3. José Torres Peña
  4. Beatriz Sánchez Moreno
  5. Francisco Arnalich
  6. María García Blanco
  7. José López Miranda
  8. Juan Romero-Cabrera
  9. Carmen Herrero Gil
  10. José Bascunana
  11. Manuel Rubio-Rivas
  12. Sara Pintos Otero
  13. Verónica Martínez Sempere
  14. Jesús Ballano Rodríguez-Solís
  15. Ricardo Gil Sánchez
  16. Jairo Luque del Pino
  17. Amara González Noya
  18. María Navas-Alcántara
  19. Begoña Cortés Rodríguez
  20. José Alcalá
  21. Ana Suárez-Lombraña
  22. Jorge Andrés Soler
  23. Ricardo Gómez-Huelgas
  24. José Casas-Rojo
  25. Jesús Millán Núñez-Cortés
  26. on behalf of the SEMI-COVID-19 Network

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Abstract

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality (p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis (p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63–0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62–0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continued treatment, and those taking ARB.

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  1. Version published to 10.3390/jcm10122642
  2. ScreenIT

    SciScore for 10.1101/2021.02.24.21252391: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics: The SEMI-COVID-19 Registry was evaluated and approved by the Provincial Research Ethics Committee of Málaga.
    Consent: Given the state of emergency declared during the pandemic, it was only mandatory for patients to provide verbal consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    On this analysis, we considered the same composite outcomes of prognosis and MACE.
    MACE
    suggested: (MACE, RRID:SCR_005520)

    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:
    This study also has several limitations. First, its retrospective and observational nature. Second, the decision to maintain or withdraw treatment during hospitalization depended on each attending physician’s judgment, leading to selection bias. Third, we do not know which ACEI or ARB drugs were used, at what doses, and for how long. Lastly, this series mainly comprises Caucasian patients, so our results cannot be extrapolated to other populations. In conclusion, our results show that maintaining treatment with ACEI/ARB in patients hospitalized for COVID-19 led to lower rates of death and respiratory complications, especially in hypertensive patients. Prospective and randomized controlled trials are needed to confirm these results. This work also points to an exciting field of research to be explored further: analysis of the molecular mechanisms that underlie the protective effect of ACEI/ARB against SARS-CoV-2.

    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.

  3. Version published to 10.1101/2021.02.24.21252391v1 on medRxiv