Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study

Aims To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19). Methods A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospit...

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Bibliographic Details
Authors: Hoertel, N., Sánchez Rico, M., Gulbins, E., Kornhuber, J., Vernet, R., Beeker, N., Neuraz, A., Blanco, C., Olfson, M., Airagnes, G., Lemogne, C., Alvarado Izquierdo, Jesús María, Arnaout, M., Cougoule, C., Meneton, P., Limosin, F.
Format: article
Publication Date:2022
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/71571
Online Access:https://hdl.handle.net/20.500.14352/71571
Access Level:Open access
Keyword:Benzodiazepine
COVID-19
mortality
SARS-CoV-2
Inmunología
Salud pública (Medicina)
2412 Inmunología
3212 Salud Pública
Description
Summary:Aims To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19). Methods A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (S.D.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Results Over a mean follow-up of 14.5 days (S.D. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74–3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31–1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08–2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment. Conclusions BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.