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

Liam Rose¹, Laura Graham¹, Allison Koenecke²

¹Department of Veterans Affairs Health Economics Resource Center, Palo Alto VA, Menlo Park, CA, United States.

Frontiers in Medicine

|April 19, 2021

Summary

Alpha-1 adrenergic receptor antagonists (α1-AR antagonists) showed a significant association with reduced COVID-19 mortality. These findings support further clinical trials for α1-AR antagonists in treating COVID-19 patients.

Keywords:

COVID-19 alpha-1-adrenergic receptor antagonist coronavirus disease infectious disease off-label drug use

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Area of Science:

Pharmacology
Infectious Diseases
Cardiovascular Medicine

Background:

The COVID-19 pandemic necessitates novel therapeutic strategies.
Pre-clinical data indicate alpha-1 adrenergic receptor antagonists (α1-AR antagonists) may mitigate hyperinflammation-related mortality.
The role of α1-AR antagonists in COVID-19 outcomes requires investigation.

Purpose of the Study:

To assess the association between baseline α1-AR antagonist use and COVID-19 mortality.
To evaluate the impact of specific α1-AR antagonists on in-hospital and 28-day mortality.

Main Methods:

Retrospective cohort study utilizing the Department of Veterans Affairs healthcare system.
Doubly robust regression and matching techniques were employed.
Analysis included patients with an active prescription for α1-AR antagonists at admission.

Main Results:

α1-AR antagonist use was linked to a significant reduction in in-hospital mortality (RRR 18%, OR 0.73) and 28-day mortality (RRR 17%, OR 0.74).
Doxazosin specifically showed a substantial risk reduction for death (RRR 74%, OR 0.23) compared to controls.
Statistical significance was observed for all primary findings (p ≤ 0.001 for general use, p = 0.028 for doxazosin).

Conclusions:

Baseline use of α1-AR antagonists is associated with decreased mortality in COVID-19 patients.
Doxazosin demonstrates a particularly strong association with reduced mortality.
Randomized, placebo-controlled trials are warranted to confirm these findings and explore therapeutic potential.