The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality From COVID-19

Frontiers in Medicine

Michael Powell¹  Brett Mench¹  Joshua T. Vogelstein²  Ruoxuan Xiong³  Zhu Shen⁴  Laura Graham⁵  Liam Rose⁵  Todd H. Wagner⁶  Allison Koenecke⁷  Bert Vogelstein⁸  Kenneth W. Kinzler⁸  Chetan Bettegowda⁹  Maximilian F. Konig^1,10  Susan Athey^1,11 

[1] Department of Biomedical Engineering, Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD, United States;Department of Biomedical Engineering, Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD, United States;Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health at The Johns Hopkins University, Baltimore, MD, United States;Department of Management Science and Engineering, Stanford University, Stanford, CA, United States;Department of Statistics, Stanford University, Stanford, CA, United States;Department of Veterans Affairs Health Economics Resource Center, Palo Alto VA, Menlo Park, CA, United States;Department of Veterans Affairs Health Economics Resource Center, Palo Alto VA, Menlo Park, CA, United States;Department of Surgery, Stanford University, Stanford, CA, United States;Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA, United States;Lustgarten Laboratory, Ludwig Center, Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, MD, United States;Lustgarten Laboratory, Ludwig Center, Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, MD, United States;Department of Neurosurgery and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States;Lustgarten Laboratory, Ludwig Center, Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, MD, United States;Division of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States;Stanford Graduate School of Business, Stanford University, Stanford, CA, United States;

关键词: COVID-19;    coronavirus disease;    alpha-1-adrenergic receptor antagonist;    infectious disease;    off-label drug use;   

DOI  :  10.3389/fmed.2021.637647

来源: Frontiers

【 摘 要 】

Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and pre-clinical data suggest alpha-1 adrenergic receptor antagonists (α1-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 α1-AR antagonists and likelihood of death due to COVID-19 during hospitalization. Having an active prescription for any α1-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 α1-AR antagonist at the time of admission. These findings suggest that use of α1-AR antagonists may reduce mortality in COVID-19, supporting the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.

【 授权许可】

CC BY