Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar;23(3):476-485.
doi: 10.1002/ejhf.2060. Epub 2020 Dec 7.

Association between renin-angiotensin-aldosterone system inhibitor use and COVID-19 hospitalization and death: a 1.4 million patient nationwide registry analysis

Gianluigi Savarese  1   2 , Lina Benson  1 , Johan Sundström  3 , Lars H Lund  1   2
Affiliations

Association between renin-angiotensin-aldosterone system inhibitor use and COVID-19 hospitalization and death: a 1.4 million patient nationwide registry analysis

Gianluigi Savarese et al. Eur J Heart Fail. 2021 Mar.

Abstract

Aims: Renin-angiotensin-aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID-19). We investigated the association between use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID-19 hospitalization/death in a large nationwide population.

Methods and results: Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020. COVID-19 cases were defined based on hospitalization/death for COVID-19. Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID-19 in the overall population, and of all-cause mortality in COVID-19 cases. We performed consistency analysis to quantify the impact of potential unmeasured confounding. Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID-19. After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID-19 (odds ratio 0.86, 95% confidence interval 0.81-0.91) in the overall population, and with reduced mortality in COVID-19 cases (hazard ratio 0.89, 95% confidence interval 0.82-0.96). MRA use was not associated with risk of any outcome. Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use.

Conclusions: In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID-19.

Keywords: Angiotensin receptor blockers; Angiotensin-converting enzyme inhibitors; COVID-19; Coronavirus; Mineralocorticoid receptor antagonists; Registry; Renin-angiotensin-aldosterone system inhibitors; SARS-CoV-2; Sweden.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Kaplan–Meier curves for risk of incident hospitalization/death for COVID‐19 in patients receiving vs. not receiving (A) angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) and (B) mineralocorticoid receptor antagonists (MRA). CI, confidence interval; HR, hazard ratio.
Figure 2
Figure 2
Impact of potential unmeasured confounders on the association between use of renin–angiotensin system inhibitors and risk of (A) incident hospitalization/death for COVID‐19 and (B) all‐cause death in COVID‐19 cases. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; CI, confidence interval; HR, hazard ratio; OR, odds ratio.
Figure 3
Figure 3
Impact of potential unmeasured confounders on the association between use of mineralocorticoid receptor antagonists (MRA) and risk of (A) incident hospitalization/death for COVID‐19 and (B) all‐cause death in COVID‐19 cases. CI, confidence interval; HR, hazard ratio; OR, odds ratio.
Figure 4
Figure 4
Subgroup analyses for the association between use of renin–angiotensin system inhibitors/mineralocorticoid receptor antagonists (MRA) and risk of hospitalization/death for COVID‐19. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; CI, confidence interval; HF, heart failure; IHD, ischaemic heart disease.
See this image and copyright information in PMC

Comment in

References

    1. Vaduganathan M, Vardeny O, Michel T, McMurray JJ, Pfeffer MA, Solomon SD. Renin‐angiotensin‐aldosterone system inhibitors in patients with Covid‐19. N Engl J Med 2020;382:1653–1659. - PMC - PubMed
    1. European Society of Cardiology . Position Statement of the ESC Council on Hypertension on ACE‐inhibitors and Angiotensin Receptor Blockers. https://www.escardio.org/Councils/Council‐on‐Hypertension‐(CHT)/News/pos... (8 July 2020).
    1. American College of Cardiology . HFSA/ACC/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID‐19. https://www.acc.org/latest‐in‐cardiology/articles/2020/03/17/08/59/hfsa‐... (8 July 2020).
    1. Lipsitch M, Swerdlow DL, Finelli L. Defining the epidemiology of Covid‐19 – studies needed. N Engl J Med 2020;382:1194–1196. - PubMed
    1. Reynolds HR, Adhikari S, Pulgarin C, Troxel AB, Iturrate E, Johnson SB, Hausvater A, Newman JD, Berger JS, Bangalore S, Katz SD, Fishman GI, Kunichoff D, Chen Y, Ogedegbe G, Hochman JS. Renin‐angiotensin‐aldosterone system inhibitors and risk of Covid‐19. N Engl J Med 2020;382:2441–2448. - PMC - PubMed

Publication types

Substances