The association between treatment with heparin and survival in patients with Covid-19

  1. Luis Ayerbe
  2. Carlos Risco
  3. Salma Ayis

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Abstract

This study investigates the association between the treatment with heparin and mortality in patients admitted with Covid-19. Routinely recorded, clinical data, up to the 24th of April 2020, from the 2075 patients with Covid-19, admitted in 17 hospitals in Spain between the 1st of March and the 20th of April 2020 were used. The following variables were extracted for this study: age, gender, temperature, and saturation of oxygen on admission, treatment with heparin, hydroxychloroquine, azithromycin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, together with data on mortality. Multivariable logistic regression models were used to investigate the associations. At the time of collecting the data, 301 patients had died, 1447 had been discharged home from the hospitals, 201 were still admitted, and 126 had been transferred to hospitals not included in the study. Median follow up time was 8 (IQR 5–12) days. Heparin had been used in 1734 patients. Heparin was associated with lower mortality when the model was adjusted for age and gender, with OR (95% CI) 0.55 (0.37–0.82) p = 0.003. This association remained significant when saturation of oxygen < 90%, and temperature > 37 °C were added to de model with OR 0.54 (0.36–0.82) p = 0.003, and also when all the other drugs were included as covariates OR 0.42 (0.26–0.66) p < 0.001. The association between heparin and lower mortality observed in this study can be acknowledged by clinicians in hospitals and in the community. Randomized controlled trials to assess the causal effects of heparin in different therapeutic regimes are required.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.27.20114694: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Stata 14 was used for the analysis.[11] The ethics committee of HM Hospitales approved this study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe proportion of men and women for those treated and not treated with heparin was compared with chi squared tests.

    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:
    This study has strengths and limitations. Patients were not randomized and the difference in outcome may be explained by factors other than the treatment with heparin. In an effort to control for the severity of disease, or the effects of other drugs, the models were adjusted for clinical markers and other treatments. The observation of a large number of unselected patients in 17 hospitals, and the analyses run with some variations to test the consistency of the results, are also strengths of this study. However, residual confounding is always present in all observational research. For all models the sensitivity analyses described in the methods were used to assess the impact of missing data on the two severity markers, and results were consistent with those presented. While the nature of the hypoperfusion of lungs in Covid-19 patients is still not fully understood, our findings support that there is a thrombotic component in the development of respiratory distress for these patients.[6, 8] The association between heparin and survival is consistent with the findings of an observational study where among the 99 patients who received heparin, and had a sepsis-induced coagulopathy index>4, mortality was significantly lower.[12] A recent observational study conducted in a hospital has also reported lower mortality among the 786 Covid-19 patients who received anticoagulation.[13] To the best of our knowledge, there is no interventional evidence on the management of the coagulopath...

    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 10.1007/s11239-020-02162-z
  3. Version published to 10.1101/2020.05.27.20114694 on medRxiv