Risk of Covid-19-Related Hospitalization and More Severe Outcomes in Medicare Beneficiaries Treated with Renin-Angiotensin-Aldosterone System Inhibitors for Hypertension

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; Thomas E MaCurdy

doi:10.1007/s11606-021-07155-z

Risk of Covid-19-Related Hospitalization and More Severe Outcomes in Medicare Beneficiaries Treated with Renin-Angiotensin-Aldosterone System Inhibitors for Hypertension

J Gen Intern Med. 2021 Dec;36(12):3802-3809. doi: 10.1007/s11606-021-07155-z. Epub 2021 Oct 1.

Authors

David J Graham¹, Hector S Izurieta², Stella G Muthuri³, Di Zhang⁴, Alexander T Sandhu^{3

5}, Yun Lu⁶, Yueqin Zhao⁴, Yuhui Feng³, Efe Eworuke⁷, Hai Lyu³, Charu Gandotra⁸, Elizabeth R Smith³, Armen Avagyan³, Michael Wernecke³, Jeffrey A Kelman⁹, Richard A Forshee⁶, Thomas E MaCurdy^{3

10}

Affiliations

¹ 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.
² Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
³ Acumen LLC, Burlingame, CA, USA.
⁴ Office of Biostatistics, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
⁵ Division of Cardiology, Department of Medicine, Stanford University, Stanford, CA, USA.
⁶ Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
⁷ 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.
⁸ Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
⁹ Centers for Medicare & Medicaid Services, Washington, DC, USA.
¹⁰ Department of Economics, Stanford University, Stanford, CA, USA.

Abstract

Background: There are theoretical concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could increase the risk of severe Covid-19.

Objective: To 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.

Design: Observational case-control study.

Participants: Medicare beneficiaries aged ≥ 66 years with hypertension, treated with ACEIs, ARBs, calcium channel blockers (CCBs), or thiazide diuretics.

Main measures: Adjusted 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.

Results: A 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).

Conclusions: ACEIs 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.

Keywords: Covid-19; angiotensin receptor blockers; angiotensin-converting enzyme inhibitors; intensive care; mechanical ventilation.

Publication types

Observational Study
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Aged
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
COVID-19*
Case-Control Studies
Female
Hospitalization
Humans
Hypertension* / drug therapy
Hypertension* / epidemiology
Medicare
Renin-Angiotensin System
SARS-CoV-2
United States / epidemiology

Substances

Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors

Grants and funding

Inter-agency agreement/U.S. Food and Drug Administration