Clinical outcomes of COVID-19 following the use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among patients with hypertension in Korea: a nationwide study

  1. Ju Hwan Kim
  2. Yeon-Hee Baek
  3. Hyesung Lee
  4. Young June Choe
  5. Hyun Joon Shin
  6. Ju-Young Shin

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Abstract

OBJECTIVES: Recent evidence has shown no harm associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). We sought to further clarify the possible association between ACEI/ARB use and the risk of poor clinical outcomes of COVID-19.METHODS: From the completely enumerated COVID-19 cohort in Korea, we identified 1,290 patients with hypertension, of whom 682 had and 603 did not have records of ACEI/ARB use during the 30-day period before their COVID-19 diagnosis. Our primary endpoint comprised clinical outcomes, including all-cause mortality, use of mechanical ventilation, intensive care unit admission, and sepsis. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and a Poisson regression model to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for comparing outcomes between ACEI/ARB users and non-users.RESULTS: Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW-adjusted RR, 0.60; 95% CI, 0.42 to 0.85; p=0.005). For individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW-adjusted RR, 0.62; 95% CI, 0.35 to 1.09; p=0.097) or respiratory events (IPTW-adjusted RR, 0.99; 95% CI, 0.84 to 1.17; p=0.904). Subgroup analysis showed a trend toward a protective role of ACEIs and ARBs against overall outcomes in men (IPTW-adjusted RR, 0.84; 95% CI, 0.69 to 1.03; p<sub>interaction</sub>=0.008) and patients with pre-existing respiratory disease (IPTW-adjusted RR, 0.74; 95% CI, 0.60 to 0.92; p<sub>interaction</sub>=0.002).CONCLUSIONS: We present clinical evidence to support continuing ACE/ARB use in COVID-19 patients with hypertension based on the completely enumerated Korean cohort.

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    SciScore for 10.1101/2020.07.29.20164822: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Our study complies with the Declaration of Helsinki and the study protocol was approved by the Institutional Review Board (IRB) of Sungkyunkwan University (SKKU 2020-03-021) and obtaining informed consent was waived by the IRB.
    Consent: Our study complies with the Declaration of Helsinki and the study protocol was approved by the Institutional Review Board (IRB) of Sungkyunkwan University (SKKU 2020-03-021) and obtaining informed consent was waived by the IRB.
    Randomizationnot detected.
    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: We detected the following sentences addressing limitations in the study:
    Our study also has some limitations. First, potential misclassification of diagnosis-based outcomes (sepsis and respiratory events) may present. Nevertheless, a validation study comparing diagnoses in the South Korean healthcare database with electronic medical records reported an overall positive predictive value of 82% 27. Death records and procedure codes including mechanical ventilation and ICU admission have high validity, and thus less likely to affect our study conclusion. Second, there is a potential exposure misclassification owing to short exposure ascertainment period. We found consistent result with the main analysis when the exposure risk window was redefined as 180 days. Third, residual confounding from unmeasured confounders (e.g. smoking history, body mass index, baseline blood pressure and laboratory test results) may have affected our results given inherent limitation of available variables in the analysis of health claims data. Finally, we included prevalent users of ACEI/ARB, while ideally new-user design is recommended where all study subjects are naïve to previous use of ACEI/ARB to address potential under ascertainment of events that occur early in therapy and to precisely control for confounders that may be altered by the study drug 28. However, we used a prevalent user cohort of ACEI/ARB given that a new-user design would exclude the large number of subjects that may represent clinically relevant subset. In conclusion, our study findings did not ident...

    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.

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  2. Version published to 10.4178/epih.e2021004
  3. Version published to 10.1101/2020.07.29.20164822v1 on medRxiv