Association of Renin Angiotensin System Blockers with Outcomes in Patients with Covid-19: A Systematic Review and Meta-analysis

  1. Aakash Garg
  2. Amit Rout
  3. Abhishek Sharma
  4. Brittany Fiorello
  5. John B. Kostis

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Abstract

Background

Patients with cardiovascular disease are at increased risk of critical illness and mortality from Covid-19 disease. Conflicting findings have raised concerns regarding the association of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) use with likelihood or severity of infection during this pandemic.

Objective

To study the cumulative evidence for association of ACEI/ARB use with outcomes among patients with confirmed Covid-19.

Methods

The MEDLINE and EMBASE databases were thoroughly searched from November 01, 2019 to May 15, 2020 for studies reporting on outcomes based on ACEI/ARB use in patients with confirmed Covid-19. Preferred reporting items for systematic review and meta-analysis guidelines were used for the present study. Relevant data was collected and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects model.

Main Outcome measures

In-hospital mortality was the primary end of interest. Second end-point was severe or critical illness defined as either need for intensive care unit, invasive mechanical ventilation, or mortality.

Results

Fifteen studies with total of 23,822 patients (N ACEI/ARB=6,650) were included in the present analysis. Overall, prevalence of ACEI/ARB use ranged from 7.7% to 46.2% across studies. Among 10 studies, patients using ACEI/ARB had similar odds of mortality [OR 1.03 (0.69-1.55)] and severe or critical illness [1.18 (0.91-1.54)] compared to those not on ACEI/ARB. In an analysis restricted to patients with hypertension, ACEI/ARB use was associated with significantly lower mortality [0.64 (0.45-0.89)], while the odds of severe/critical illness [0.76(0.52-1.12); p=0.16] remained non-significant compared with non-ACEI/ARB users.

Conclusion

There is no evidence for increased risk of severe illness or mortality in patients using ACEI/ARB compared with non-users. In patients with hypertension, ACE/ARB use might be associated with reduced mortality, however these findings need to be confirmed in prospective randomized controlled trials.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.23.20111401: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    A comprehensive search in electronic databases (MEDLINE and EMBASE) was performed of studies published between November 01, 2019 and May 15, 2020, and reporting outcomes among Covid-19 patients on RAS inhibitors.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)

    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:
    There are several limitations to our study. First, our pooled analyses were based on observational studies that have inherent risk of bias due to confounding variables. Patients taking ACEI/ARBs have increased burden of other comorbidities that might make them more prone to fatality. However, despite this potential bias, we observed no association of ACEI/ARB use with increased risk of mortality or severe illness. Second, ascertainment of drug data is limited in individual retrospective studies. It remains unknown whether continuation or withdrawal of these drugs during hospitalization influenced outcomes in patients admitted with Covid-19. In conclusion, our study provides reassurance that there is no increased risk of mortality or severe illness in patients using ACEI/ARB compared to non-users. Given the high prevalence of CV disease and complications in Covid-19, continuation of RAS inhibitors should be encouraged and eventually driven by clinical judgment. On-going RCTs will further inform the safety and efficacy of these drugs in HTN patients with Covid-19 disease.

    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 10.1101/2020.05.23.20111401v1 on medRxiv