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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

¹VA Health Economics Resource Center, Palo Alto VA, Menlo Park, CA, USA.

Medrxiv : the Preprint Server for Health Sciences

|January 5, 2021

Summary

Alpha-1 adrenergic receptor antagonists (α1-AR antagonists) may reduce COVID-19 mortality. This study found α1-AR antagonist use was associated with lower in-hospital and 28-day mortality in veterans with COVID-19.

Keywords:

COVID-19 SARS-CoV-2 alpha-1 adrenergic receptor antagonist catecholamine doxazosin hyperinflammation in-hospital mortality retrospective cohort study

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Area of Science:

Pharmacology
Infectious Diseases
Cardiovascular Medicine

Background:

Effective COVID-19 therapies are needed.
Preclinical data suggest alpha-1 adrenergic receptor antagonists (α1-AR antagonists) may mitigate hyperinflammation-related mortality.
α1-AR antagonists are used to treat conditions like hypertension and benign prostatic hyperplasia.

Approach:

Retrospective cohort study design.
Utilized data from the Department of Veterans Affairs healthcare system.
Employed doubly robust regression and matching to assess the association between α1-AR antagonist use and COVID-19 mortality.

Key Points:

Baseline α1-AR antagonist prescription was linked to a significant reduction in in-hospital mortality (18% RR reduction) and 28-day mortality (17% RR reduction).
Patients specifically on doxazosin, an inhibitor of all three α1-AR subtypes, showed a substantial 74% relative risk reduction in mortality compared to controls.
The findings highlight a potential protective effect of α1-AR antagonists against COVID-19 mortality.

Conclusions:

α1-AR antagonist use may be associated with reduced mortality in patients hospitalized with COVID-19.
These results support the initiation of randomized, placebo-controlled clinical trials to investigate the efficacy of α1-AR antagonists in early symptomatic COVID-19 infections.