Association of α1-Blocker Receipt with 30-Day Mortality and Risk of Intensive Care Unit Admission among Adults Hospitalized with Influenza or Pneumonia in Denmark

Abstract

Importance: Alpha 1-adrenergic receptor blocking agents (α1-blockers) have been reported to have protective benefits against hyperinflammation and cytokine storm syndrome, conditions that are associated with mortality in patients with coronavirus disease 2019 and other severe respiratory tract infections. However, studies of the association of α1-blockers with outcomes among human participants with respiratory tract infections are scarce. Objective: To examine the association between the receipt of α1-blockers and outcomes among adult patients hospitalized with influenza or pneumonia. Design, Setting, and Participants: This population-based cohort study used data from Danish national registries to identify individuals 40 years and older who were hospitalized with influenza or pneumonia between January 1, 2005, and November 30, 2018, with follow-up through December 31, 2018. In the main analyses, patients currently receiving α1-blockers were compared with those not receiving α1-blockers (defined as patients with no prescription for an α1-blocker filled within 365 days before the index date) and those currently receiving 5α-reductase inhibitors. Propensity scores were used to address confounding factors and to compute weighted risks, absolute risk differences, and risk ratios. Data were analyzed from April 21 to December 21, 2020. Exposures: Current receipt of α1-blockers compared with nonreceipt of α1-blockers and with current receipt of 5α-reductase inhibitors. Main Outcomes and Measures: Death within 30 days of hospital admission and risk of intensive care unit (ICU) admission. Results: A total of 528467 adult patients (median age, 75.0 years; interquartile range, 64.4-83.6 years; 273005 men [51.7%]) were hospitalized with influenza or pneumonia in Denmark between 2005 and 2018. Of those, 21772 patients (4.1%) were currently receiving α1-blockers compared with a population of 22117 patients not receiving α1-blockers who were weighted to the propensity score distribution of those receiving α1-blockers. In the propensity score-weighted analyses, patients receiving α1-blockers had lower 30-day mortality (15.9%) compared with patients not receiving α1-blockers (18.5%), with a corresponding risk difference of -2.7% (95% CI, -3.2% to -2.2%) and a risk ratio (RR) of 0.85 (95% CI, 0.83-0.88). The risk of ICU admission was 7.3% among patients receiving α1-blockers and 7.7% among those not receiving α1-blockers (risk difference, -0.4% [95% CI, -0.8% to 0%]; RR, 0.95 [95% CI, 0.90-1.00]). A comparison between 18280 male patients currently receiving α1-blockers and 18228 propensity score-weighted male patients currently receiving 5α-reductase inhibitors indicated that those receiving α1-blockers had lower 30-day mortality (risk difference, -2.0% [95% CI, -3.4% to -0.6%]; RR, 0.89 [95% CI, 0.82-0.96]) and a similar risk of ICU admission (risk difference, -0.3% [95% CI, -1.4% to 0.7%]; RR, 0.96 [95% CI, 0.83-1.10]). Conclusions and Relevance: This cohort study's findings suggest that the receipt of α1-blockers is associated with protective benefits among adult patients hospitalized with influenza or pneumonia..