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The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality From COVID-19.
Rose L, Graham L, Koenecke A, Powell M, Xiong R, Shen Z, Mench B, Kinzler KW, Bettegowda C, Vogelstein B, Athey S, Vogelstein JT, Konig MF, Wagner TH. The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality From COVID-19. Frontiers in medicine. 2021 Mar 31; 8:637647.
Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and pre-clinical data suggest alpha-1 adrenergic receptor antagonists ( -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 -AR antagonists and likelihood of death due to COVID-19 during hospitalization. Having an active prescription for any -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; 0.001) and death within 28 days of admission (relative risk reduction 17%; odds ratio 0.74; 95% CI 0.65-0.84; 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; = 0.028) compared to matched controls not on any -AR antagonist at the time of admission. These findings suggest that use of -AR antagonists may reduce mortality in COVID-19, supporting the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.