• Am. J. Med. · Oct 2023

    Risk of severe Covid-19 in prevalent users of α-1 adrenergic receptor antagonists: a national case-control study of Medicare beneficiaries.

    • David J Graham, Hector S Izurieta, Di Zhang, Armen Avagyan, Hai Lyu, Roger Wiederhorn, Yun Lu, Andrew D Mosholder, Elizabeth R Smith, Yueqin Zhao, Shanlai Shangguan, Huei-Ting Tsai, Dinci Pennap, Alexander T Sandhu, Michael Wernecke, Thomas E MaCurdy, Jeffrey A Kelman, and Richard A Forshee.
    • Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Md. Electronic address: david.graham1@fda.hhs.gov.
    • Am. J. Med. 2023 Oct 1; 136 (10): 10181025.e31018-1025.e3.

    BackgroundAlpha-1 adrenergic receptor antagonists prevent cytokine storm in mouse sepsis models. This led to the hypothesis that alpha-1 blockers may prevent severe coronavirus disease 2019 (COVID-19), which is characterized by hypercytokinemia and progressive respiratory failure.MethodsWe performed an observational case-control study in male Medicare beneficiaries aged 65 years or older, with or without benign prostatic hyperplasia (BPH), and treated with alpha-1 receptor blockers or 5-alpha reductase inhibitors. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated for outcomes of uncomplicated and severe COVID-19 hospitalization (intensive care unit admission, invasive mechanical ventilation, or death).ResultsThere were 20,963 cases of hospitalized COVID-19 matched to 101,161 controls on calendar date and neighborhood of residence. In the primary analysis (males with BPH), there was no difference in risk of uncomplicated COVID-19 hospitalization (aOR 1.08, 95% CI 0.996-1.17) or hospitalization with severe complications (aOR 0.97, 95% CI 0.88-1.08). In the secondary analysis (males with or without BPH), the corresponding aORs were 1.02 (95% CI, 0.96-1.09) (uncomplicated) and 0.99 (95% CI, 0.91-1.07) (complicated), respectively. Subgroup and sensitivity analyses yielded similar results. Of note, there was no difference in risk of severe COVID-19 hospitalization when comparing non-selective vs selective alpha-1 blocker use (aOR 0.98, 95% CI 0.86-1.10), higher- vs lower-dose alpha-1 blocker use (aOR 0.96, 95% CI 0.86-1.08), or current vs remote alpha-1 blocker use (aOR 1.04, 95% CI 0.91-1.18).ConclusionsPrevalent use of alpha-1 receptor blockers was not associated with a protective or harmful effect on risk of uncomplicated or severe hospitalized COVID-19.Published by Elsevier Inc.

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