Association of Statins and 28-Day Mortality Rates in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

  1. Zoe N Memel
  2. Jenny J Lee
  3. Andrea S Foulkes
  4. Raymond T Chung
  5. Tanayott Thaweethai
  6. Patricia P Bloom

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Abstract

Background

Statins may be protective in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. The aim of the current study was to evaluate the effect of in-hospital statin use on 28-day mortality rates and intensive care unit (ICU) admission among patients with SARS-CoV-2, stratified into 4 groups: those who used statins before hospitalization (treatment continued or discontinued in the hospital) and those who did not (treatment newly initiated in the hospital or never initiated).

Methods

In a cohort study of 1179 patients with SARS-CoV-2, record review was used to assess demographics, laboratory measurements, comorbid conditions, and time from admission to death, ICU admission, or discharge. Using marginal structural Cox models, we estimated hazard ratios (HRs) for death and ICU admission.

Results

Among 1179 patients, 676 (57%) were male, 443 (37%) were >65 years old, and 493 (46%) had a body mass index ≥30 (calculated as weight in kilograms divided by height in meters squared). Inpatient statin use reduced the hazard of death (HR, 0.566; P=.008). This association held among patients who did and those who did not use statins before hospitalization (HR, 0.270 [P=.003] and 0.493 [P=.04], respectively). Statin use was associated with improved time to death for patients aged >65 years but not for those ≤65 years old.

Conclusion

Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates. Well-designed randomized control trials are needed to better define this relationship.

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  1. Version published to 10.1093/infdis/jiab539
  2. ScreenIT

    SciScore for 10.1101/2021.03.27.21254373: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the local Institutional Review Board (IRB # 2020P000829); a waiver of informed consent was granted.
    Consent: This study was approved by the local Institutional Review Board (IRB # 2020P000829); a waiver of informed consent was granted.
    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:
    Despite these limitations, there is no clear evidence that statin exposure during infection is associated with clinically important hepatotoxicity. Myotoxicity is a known, albeit rare, complication of statins. In the context of COVID-19, where creatinine kinase elevations are prevalent, there is concern that statins could increase myotoxicity and subsequent creatinine kinase-induced nephrotoxicity. This was not seen among individuals newly initiated on statins or continued on statin therapy, with creatinine kinase peak levels never reaching three times the upper limit of normal, clinically considered the threshold for acute kidney injury due to pigment associated nephropathy (46). Our findings must be interpreted in the context of study design. Although we utilized two data sources to confirm demographics, medications, laboratory data and clinical outcomes, misclassification errors are possible. We limited this error rate by employing physician review of discrepant data. Additionally, we were unable to account for patients who had dose escalations in their statin usage or who had their statin temporarily held during hospitalization. It is important to note that peak liver biochemistry levels (AST and ALT) as well as peak CK level were compared with unadjusted analyses and timing of statin initiation was not taken into account. Finally, patients who were on statin therapy prior to hospitalization but had the medication discontinued during hospitalization, presumably due to org...

    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 10.1101/2021.03.27.21254373 on medRxiv