Frontiers in Medicine (Mar 2021)

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

  • Liam Rose,
  • Laura Graham,
  • Allison Koenecke,
  • Michael Powell,
  • Ruoxuan Xiong,
  • Zhu Shen,
  • Brett Mench,
  • Kenneth W. Kinzler,
  • Chetan Bettegowda,
  • Chetan Bettegowda,
  • Bert Vogelstein,
  • Susan Athey,
  • Joshua T. Vogelstein,
  • Joshua T. Vogelstein,
  • Maximilian F. Konig,
  • Maximilian F. Konig,
  • Todd H. Wagner,
  • Todd H. Wagner

DOI
https://doi.org/10.3389/fmed.2021.637647
Journal volume & issue
Vol. 8

Abstract

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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.

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