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

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.