Antecedent use of renin-angiotensin system inhibitors is associated with reduced mortality in elderly hypertensive Covid-19 patients

  1. Mauro Gori
  2. Carlo Berzuini
  3. Emilia D’Elia
  4. Arianna Ghirardi
  5. Luisa Bernardinelli
  6. Antonello Gavazzi
  7. Giulio Balestrieri
  8. Andrea Giammarresi
  9. Roberto Trevisan
  10. Fabiano Di Marco
  11. Antonio Bellasi
  12. Mariangela Amoroso
  13. Federico Raimondi
  14. Luca Novelli
  15. Bianca Magro
  16. Gianpaolo Mangia
  17. Ferdinando L. Lorini
  18. Giulio Guagliumi
  19. Stefano Fagiuoli
  20. Gianfranco Parati
  21. Michele Senni

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Abstract

The effect of renin-angiotensin system inhibitors (RASIs) on mortality in patients with coronavirus disease (Covid-19) is debated. From a cohort of 1352 consecutive patients admitted with Covid-19 to Papa Giovanni XXIII Hospital in Bergamo, Italy, between February and April 2020, we selected and studied hypertensive patients to assess whether antecedent (prior to hospitalization) use of RASIs might affect mortality from Covid-19 according to age.

Methods and results:

Arterial hypertension was present in 688 patients. Overall mortality (in-hospital or shortly after discharge) was 35% ( N  = 240). After adjusting for 26 medical history variables via propensity score matching, antecedent use of RASIs ( N  = 459, 67%) was associated with a lower mortality in older hypertensive patients (age above the median of 68 years in the whole series), whereas no evidence of a significant effect was found in the younger group of the same population ( P interaction = 0.001). In an analysis of the subgroup of 432 hypertensive patients older than 68 years, we considered two RASI drug subclasses, angiotensin-converting enzyme inhibitors (ACEIs, N  = 156) and angiotensin receptor blockers (ARBs, N  = 140), and assessed their respective effects by taking no-antecedent-use of RASIs as reference. This analysis showed that both antecedent use of ACEIs and antecedent use of ARBs were associated with a lower Covid-19 mortality (odds ratio ACEI  = 0.57, 95% confidence interval 0.36--0.91, P  = 0.018) (odds ratio ARB  = 0.49, 95% confidence interval 0.29--0.82, P  = 0.006).

Conclusion:

In the population of over-68 hypertensive Covid-19 patients, antecedent use of ACEIs or ARBs was associated with a lower all-cause mortality, whether in-hospital or shortly after discharge, compared with no-antecedent-use of RASIs.

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  1. Version published to 10.1097/hjh.0000000000003059
  2. ScreenIT

    SciScore for 10.1101/2020.12.15.20247999: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics: Necessary approval was obtained from the Bergamo Ethics Committee (n. 37/2020) with operating center at the Papa Giovanni XXIII Hospital of Bergamo, which has capacity to give its opinion on studies conducted in a number of health care structures in the Bergamo area of the north-italian region Lom bardia, including the mentioned hospital, ten “Aziende Socio Sanitarie Territoriali” and fourteen “Agenzie di Tutela della Salute”.
    Consent: In conformity with local protocol, consent was obtained from the patient.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Laboratory confirmation of SARS-CoV-2 infection via SARS-CoV-2 genome detection from nasal swab and respiratory samples was obtained through two different molecular methods (GeneFinder COVID-19-Elitech Group, Allplex™2019-nCoV Assay-Seegene Inc) following instructions.
    GeneFinder
    suggested: (GENEFINDER, RRID:SCR_009190)

    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:
    Strength and Limitations: Our study was based on a single big hospital. Rather than a limitation, this may be an element of strength of the study, insofar as homogeneity of target population reduces potential biases. Two characteristics of our cohort, high percentage of elderly hypertensives and peak Covid-19 lethality, enhanced our power to detect the effects of interest. We have used propensity-score matching methods to create exposure comparison groups that are comparable with respect to observed potential confounders. Despite the rather large number of medical history variables involved in the construction of our propensity scores, there may be additional unmeasured confounders that have not been taken into account, and consequently affect our results.

    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 10.1101/2020.12.15.20247999v1 on medRxiv