key: cord-0957471-s9sdix8n
authors: Thomsen, Reimar W.; Christiansen, Christian Fynbo; Heide-Jørgensen, Uffe; Vogelstein, Joshua T.; Vogelstein, Bert; Bettegowda, Chetan; Tamang, Suzanne; Athey, Susan; Sørensen, Henrik Toft
title: 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
date: 2021-02-10
journal: JAMA Netw Open
DOI: 10.1001/jamanetworkopen.2020.37053
sha: 5398052b1a074476be0be64651b23dde3c7b73fc
doc_id: 957471
cord_uid: s9sdix8n

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 528 467 adult patients (median age, 75.0 years; interquartile range, 64.4-83.6 years; 273 005 men [51.7%]) were hospitalized with influenza or pneumonia in Denmark between 2005 and 2018. Of those, 21 772 patients (4.1%) were currently receiving α1-blockers compared with a population of 22 117 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 18 280 male patients currently receiving α1-blockers and 18 228 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.

*Note on main exposure: Alpha-1-blockers (called Alpha-adrenoreceptor Antagonists in the ATC) are ATC classified both as antihypertensives and as BPH drugs. The ATC group "C02 Antihypertensives" includes category "C02CA Alpha-adrenoreceptor Antagonists", which includes C02CA01 prazosin, C02CA02 indoramin, C02CA03 trimazosin, C02CA04 doxazosin, C02CA06 urapidil. The ATC group "G04C Drugs Used In BPH" includes category "G04CA Alpha-adrenoreceptor Antagonists", which includes G04CA01 alfuzosin, G04CA02 tamsulosin, G04CA03 terazosin, G04CA04 silodosin, as well as the combination pills G04CA51 alfuzosin and finasteride, G04CA52 tamsulosin and dutasteride, G04CA53 tamsulosin and solifenacin, G04CA54 tamsulosin and tadalafil. In Denmark, for antihypertensive treatment, mainly doxazosin ("Carduran®" and others) from the "C02 Antihypertensives" group, as well as terazosin ("Hytrin" or "Sinalfa®") from the "G04CA Drugs Used In BPH" group are used (https://pro.medicin.dk/Laegemiddelgrupper/grupper/97045). For BPH treatment, Doxazosin from the "C02 Antihypertensives" group, as well as virtually all drugs from the "G04CA Drugs Used In BPH" group are used. 

Chronic pulmonary disease

Calcium channel blockers

Nonsteroidal anti-inflammatory drugs

Hypnotics/sedatives

Lifestyle and social factors Markers of smoking