• David J Graham, Hector S Izurieta, Stella G Muthuri, Di Zhang, Alexander T Sandhu, Yun Lu, Yueqin Zhao, Yuhui Feng, Efe Eworuke, Hai Lyu, Charu Gandotra, Elizabeth R Smith, Armen Avagyan, Michael Wernecke, Jeffrey A Kelman, Richard A Forshee, and Thomas E MaCurdy.
• Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Building 22, Room 4314, Silver Spring, MD, 20993, USA. david.graham1@fda.hhs.gov.
• J Gen Intern Med. 2021 Dec 1; 36 (12): 380238093802-3809.

BackgroundThere are theoretical concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could increase the risk of severe Covid-19.ObjectiveTo determine if ACEIs and ARBs are associated with an increased risk of Covid-19 hospitalization overall, or hospitalization involving intensive care unit (ICU) admission, invasive mechanical ventilation, or death.DesignObservational case-control study.ParticipantsMedicare beneficiaries aged ≥ 66 years with hypertension, treated with ACEIs, ARBs, calcium channel blockers (CCBs), or thiazide diuretics.Main MeasuresAdjusted odds ratios (OR) and 95% confidence intervals (CI) for the outcomes of Covid-19 hospitalization, or hospitalization involving ICU admission, invasive mechanical ventilation, or death.ResultsA total of 35,300 cases of hospitalized Covid-19 were matched to 228,228 controls on calendar date and neighborhood of residence. The median age of cases was 79 years, 57.4% were female, and the median duration of hospitalization was 8 days (interquartile range 5-12). ACEIs and ARBs were associated with a slight reduction in Covid-19 hospitalization risk compared with treatment with other first-line antihypertensives (OR for ACEIs 0.95, 95% CI 0.92-0.98; OR for ARBs 0.94, 95% CI 0.90-0.97). Similar results were obtained for hospitalizations involving ICU admission, invasive mechanical ventilation, or death. There were no meaningful differences in risk for ACEIs compared with ARBs. In an analysis restricted to monotherapy with a first-line agent, CCBs were associated with a small increased risk of Covid-19 hospitalization compared with ACEIs (OR 1.09, 95% CI 1.04-1.14), ARBs (OR 1.10, 95% CI 1.05-1.15), or thiazide diuretics (OR 1.11, 95% CI 1.03-1.19).ConclusionsACEIs and ARBs were not associated with an increased risk of Covid-19 hospitalization or with hospitalization involving ICU admission, invasive mechanical ventilation, or death. The finding of a small increased risk of Covid-19 hospitalization with CCBs was unexpected and could be due to residual confounding.© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

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