Association between Hydroxyzine Use and Reduced Mortality in Patients Hospitalized for Coronavirus Disease 2019: Results from a multicenter observational study
ABSTRACT Objective To examine the association between hydroxyzine use and mortality in patients hospitalized for COVID-19, based on its anti-inflammatory and antiviral properties.Design Multicenter observational retrospective cohort study.Setting Greater Paris University hospitals, France.Participants 7,345 adults hospitalized for COVID-19 between 24 January and 1 April 2020, including 138 patients (1.9%) who received hydroxyzine during the visit at a mean dose of 49.8 mg (SD=51.5) for an average of 22.4 days (SD=25.9).Data source Assistance Publique-Hôpitaux de Paris Health Data Warehouse.Main outcome measures The study endpoint was death. We compared this endpoint between patients who received hydroxyzine and those who did not in time-to-event analyses adjusting for patient characteristics (such as age, sex, and comorbidities), clinical and biological markers of disease’s severity, and use of other medications. The primary analysis was a multivariable Cox model with inverse probability weighting. Sensitivity analyses included a multivariable Cox model and a univariate Cox regression model in a matched analytic sample in a 1:1 ratio.Results Over a mean follow-up of 20.3 days (SD=27.5), 994 patients (13.5%) had a primary end-point event. The primary multivariable analysis with inverse probability weighting showed a significant association between hydroxyzine use and reduced mortality (HR, 0.42; 95% CI, 0.25 to 0.71; p=0.001) with a significant dose-effect relationship (HR, 0.10; 95% CI, 0.02 to 0.45; p=0.003). This association was similar in sensitivity analyses. In secondary analyses conducted among subsamples of patients, we found a significant association between hydroxyzine use and a faster decrease in biological inflammatory markers associated with COVID-19-related mortality, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein ratio (LCRP), and circulating interleukin 6 levels (IL-6) (all p<0.016), with a significant dose-effect relationship for NLR and LCRP (both p<0.037).Conclusions In this retrospective observational study, hydroxyzine use was associated with reduced mortality in patients hospitalized for COVID-19. This association may be partially mediated by specific anti-inflammatory properties of H1 antihistamines. Double-blind controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 25. Nov. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hoertel, Nicolas [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2020.10.23.20154302 |
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| PPN (Katalog-ID): |
XBI019214766 |
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| 245 | 1 | 0 | |a Association between Hydroxyzine Use and Reduced Mortality in Patients Hospitalized for Coronavirus Disease 2019: Results from a multicenter observational study |
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| 520 | |a ABSTRACT Objective To examine the association between hydroxyzine use and mortality in patients hospitalized for COVID-19, based on its anti-inflammatory and antiviral properties.Design Multicenter observational retrospective cohort study.Setting Greater Paris University hospitals, France.Participants 7,345 adults hospitalized for COVID-19 between 24 January and 1 April 2020, including 138 patients (1.9%) who received hydroxyzine during the visit at a mean dose of 49.8 mg (SD=51.5) for an average of 22.4 days (SD=25.9).Data source Assistance Publique-Hôpitaux de Paris Health Data Warehouse.Main outcome measures The study endpoint was death. We compared this endpoint between patients who received hydroxyzine and those who did not in time-to-event analyses adjusting for patient characteristics (such as age, sex, and comorbidities), clinical and biological markers of disease’s severity, and use of other medications. The primary analysis was a multivariable Cox model with inverse probability weighting. Sensitivity analyses included a multivariable Cox model and a univariate Cox regression model in a matched analytic sample in a 1:1 ratio.Results Over a mean follow-up of 20.3 days (SD=27.5), 994 patients (13.5%) had a primary end-point event. The primary multivariable analysis with inverse probability weighting showed a significant association between hydroxyzine use and reduced mortality (HR, 0.42; 95% CI, 0.25 to 0.71; p=0.001) with a significant dose-effect relationship (HR, 0.10; 95% CI, 0.02 to 0.45; p=0.003). This association was similar in sensitivity analyses. In secondary analyses conducted among subsamples of patients, we found a significant association between hydroxyzine use and a faster decrease in biological inflammatory markers associated with COVID-19-related mortality, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein ratio (LCRP), and circulating interleukin 6 levels (IL-6) (all p<0.016), with a significant dose-effect relationship for NLR and LCRP (both p<0.037).Conclusions In this retrospective observational study, hydroxyzine use was associated with reduced mortality in patients hospitalized for COVID-19. This association may be partially mediated by specific anti-inflammatory properties of H1 antihistamines. Double-blind controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results. | ||
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