Alpha‐1 adrenergic antagonists and the risk of hospitalization or death in non‐hospitalized patients with COVID‐19: A population‐based study

Background Alpha‐1 receptor antagonists may interfere with IL‐6 signaling and could therefore be a potential treatment for COVID‐19. However, the effectiveness of these drugs in mitigating the risk of clinical deterioration among non‐hospitalized patients with COVID‐19 is unknown. Objectives The aim of this study is to examine the association between alpha‐1 antagonist exposure and the 30‐day risk of a hospital encounter or death in nonhospitalized patients with COVID‐19. Methods We conducted a population‐based cohort study of Ontario residents aged 35 years and older who were eligible for public drug coverage and who had a positive test for SARS‐CoV‐2 between January 1, 2020, and March 1, 2021. We matched each individual receiving an alpha‐1 antagonist at the time of their positive test with two non‐exposed individuals using propensity scores. Our outcome was a composite of a hospital admission, emergency department visit, or death, 1 to 30 days following the positive test. Results We matched 3289 alpha‐1 antagonist exposed patients to 6189 unexposed patients. Overall, there was no difference in the 30‐day risk of the primary outcome among patients exposed to alpha‐1 antagonists at the time of their diagnosis relative to unexposed individuals (28.8% vs. 28.0%; OR 1.00, 95% CI 0.91 to 1.11). In a secondary analysis, individuals exposed to alpha‐1 antagonists had a lower risk of death in the 30 days following a COVID diagnosis (OR 0.79; 95% CI 0.66 to 0.93). Conclusion Alpha‐1 antagonists did not mitigate the 30‐day risk of clinical deterioration in non‐hospitalized patients with COVID‐19. Our findings do not support the general repurposing of alpha‐1 antagonists as a treatment for such patients, although there may be subgroups of patients in whom further research is warranted.