(41) Α-1 Adrenergic Receptor Antagonists and Risk of Severe COVID-19

Publication Number: 372

Background: Studies in mice found that α-1 adrenergic receptor blockade prevented cytokine storm and greatly reduced mortality in experimental sepsis models. Severe Covid-19 is characterized by markedly increased cytokines and progressive respiratory failure. This led to the hypothesis that α-1 blockers might prevent severe Covid-19.

Objectives: To test whether prevalent use of α-1 blockers is associated with reduced risk of severe Covid-19.

Methods: We performed a case-control study within a cohort of male Medicare beneficiaries aged ≥ 65 years, enrolled in Medicare Parts A (hospitalization), B (office-based care), and D (prescription drug coverage), and diagnosed with benign prostatic hyperplasia (BPH). From April 1 to December 11, 2020, we identified as cases all cohort members with an incident ICD-10-CM hospital discharge diagnosis of Covid-19. We randomly selected up to 10 controls per case from the base population, matched on index date and neighborhood (census block or block group). Nursing home cases were matched to controls from the same facility. We defined α-1 blocker use as a prescription fill providing ≥ 15 days of supply during the 30 days prior to index date. 5-α reductase inhibitor (5-ARI) use, an alternative BPH therapy, was the comparator. The outcome of Covid-19 hospitalization had 2 levels: uncomplicated and severe (complicated by intensive care unit admission, invasive mechanical ventilation, or death. We adjusted for demographics, medical comorbidities, chronic medications, and healthcare utilization and estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable multinomial conditional logistic regression.

Results: Of 21,981 Covid-19 cases, we successfully matched 20,967 (95.4%) to 101,235 controls (4.8 controls per case). Cases were older, more likely to have lower income, to reside in a nursing home, and to have more medical comorbidities and chronic medication use. There was no difference in risk of uncomplicated Covid-19 hospitalization (OR 1.08, 95% CI 0.996-1.17) or more severe hospitalization (OR 0.98, 95% CI 0.89-1.08) in users of α-1 receptor blockers compared with 5-ARI use. There was no evidence of a differential effect in subgroups defined by age, race, nursing home status, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, and chronic kidney disease. Sensitivity analyses yielded results consistent with the primary analysis.

Conclusions: Use of α-1 blockers was not associated with a reduced risk of severe Covid-19 compared with 5-ARIs, providing evidence against the α-1 blocker hypothesis.