COVID-19 outcomes among hospitalized men with or without exposure to alpha-1-adrenergic receptor blocking agents

Importance Alpha-1-adrenergic receptor antagonists (α 1 -blockers) can abrogate pro-inflammatory cytokines and may improve outcomes among patients with respiratory infections. Repurposing readily available drugs such as α 1 -blockers could augment the medical response to the COVID-19 pandemic. Objective To evaluate the association between α 1 -blocker exposure and COVID-19 mortality Design Real-world evidence study Setting Patient level data with 32,355 records tested for SARS-CoV-2 at the Mount Sinai Health System including 8,442 laboratory-confirmed cases extracted from five member hospitals in the New York City metropolitan area. Participants 2,627 men aged 45 or older admitted with COVID-19 between February 24 and May 31, 2020 Exposures α 1 -blocker use as an outpatient or while admitted for COVID-19 Main Outcomes and Measures In-hospital mortality Results Men exposed to α 1 -blockers (N=436) were older (median age 73 vs. 64 years, P<0.001) and more likely to have comorbidities than unexposed men (N=2,191). Overall, 758 (28.9%) patients died in hospital, 1,589 (60.5%) were discharged, and 280 (10.7%) were still hospitalized as of May 31, 2020. Outpatient exposure to α 1 -blockers was not associated with COVID-19 hospital outcomes, though there was a trend towards significance (OR 0.749, 95% CI 0.527-1.064; P=0.106). Conversely, inpatient use of α 1 -blockers was independently associated with improved in-hospital mortality in both multivariable logistic (OR 0.633, 95% CI 0.434-0.921; P=0.017) and Cox regression analyses (HR 0.721, 95% CI 0.572-0.908; P=0.006) adjusting for patient demographics, comorbidities, and baseline vitals and labs. Age-stratified analyses suggested greater benefit from inpatient α 1 -blocker use among younger age groups: Age 45-65 OR 0.384, 95% CI 0.164-0.896 (P=0.027); Age 55-75 OR 0.511, 95% CI 0.297-0.880 (P=0.015); Age 65-89 OR 0.810, 95% CI 0.509-1.289 (P=0.374). Conclusions and Relevance Inpatient α 1 -blocker use was independently associated with improved COVID-19 mortality among hospitalized men. Clinical trials to assess the therapeutic value of α 1 -blockers in COVID-19 are warranted.