期刊
FRONTIERS IN MEDICINE
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmed.2021.637647
关键词
COVID-19; coronavirus disease; alpha-1-adrenergic receptor antagonist; infectious disease; off-label drug use
资金
- National Science Foundation Graduate Research Fellowship [DGE-1656518]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [T32AR048522]
- Burroughs Wellcome Career Award for Medical Scientists
- Office of Naval Research [N00014-17-1-2131]
- Virginia and D.K. Ludwig Fund for Cancer Research
- Lustgarten Foundation for Pancreatic Cancer Research
- BKI Cancer Genetics and Genomics Research Program
- VA Research Career Scientist Award [RCS-17-154]
- Microsoft Research and Fast Grants, part of the Emergent Ventures Program at The Mercatus Center at George Mason University
This study found that the use of alpha-1 adrenergic receptor antagonists may reduce mortality in COVID-19 patients, particularly those using doxazosin. It suggests the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.
Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and pre-clinical data suggest alpha-1 adrenergic receptor antagonists (alpha(1)-AR antagonists) may be effective in reducing mortality related to hyperinflammation independent of etiology. Using a retrospective cohort design with patients in the Department of Veterans Affairs healthcare system, we use doubly robust regression and matching to estimate the association between baseline use of alpha(1)-AR antagonists and likelihood of death due to COVID-19 during hospitalization. Having an active prescription for any alpha(1)-AR antagonist (tamsulosin, silodosin, prazosin, terazosin, doxazosin, or alfuzosin) at the time of admission had a significant negative association with in-hospital mortality (relative risk reduction 18%; odds ratio 0.73; 95% CI 0.63-0.85; p <= 0.001) and death within 28 days of admission (relative risk reduction 17%; odds ratio 0.74; 95% CI 0.65-0.84; p <= 0.001). In a subset of patients on doxazosin specifically, an inhibitor of all three alpha-1 adrenergic receptors, we observed a relative risk reduction for death of 74% (odds ratio 0.23; 95% CI 0.03-0.94; p = 0.028) compared to matched controls not on any alpha(1)-AR antagonist at the time of admission. These findings suggest that use of alpha(1)-AR antagonists may reduce mortality in COVID-19, supporting the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.
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