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
Multicenter Study
. 2020 Oct 20;9(19):e017297.
doi: 10.1161/JAHA.120.017297. Epub 2020 Oct 1.

Renin-Angiotensin System Blockers and Adverse Outcomes of Influenza and Pneumonia: A Danish Cohort Study

Christian Fynbo Christiansen  1 , Uffe Heide-Jørgensen  1 , Thomas Bøjer Rasmussen  1 , Jacob Bodilsen  2 , Ole Schmeltz Søgaard  3 , Michael Maeng  4 , Simon Tilma Vistisen  5   6 , Morten Schmidt  1   4   7 , Anton Pottegård  8 , Lars Christian Lund  8 , Mette Reilev  8 , Jesper Hallas  8 , Nanna Borup Johansen  9 , Nikolai Constantin Brun  9 , Henrik Toft Sørensen  1   10 , Reimar Wernich Thomsen  1
Affiliations
Multicenter Study

Renin-Angiotensin System Blockers and Adverse Outcomes of Influenza and Pneumonia: A Danish Cohort Study

Christian Fynbo Christiansen et al. J Am Heart Assoc. .

Abstract

Background Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may worsen the prognosis of coronavirus disease 2019, but any association could be confounded by the cardiometabolic conditions indicating ACE-I/ARB use. We therefore examined the impact of ACE-Is/ARBs on respiratory tract infection outcomes. Methods and Results This cohort study included all adult patients hospitalized with influenza or pneumonia from 2005 to 2018 in Denmark using population-based medical databases. Thirty-day mortality and risk of admission to the intensive care unit in ACE-Is/ARBs users was compared with nonusers and with users of calcium channel blockers. We used propensity scores to handle confounding and computed propensity score-weighted risks, risk differences (RDs), and risk ratios (RRs). Of 568 019 patients hospitalized with influenza or pneumonia, 100 278 were ACE-I/ARB users and 37 961 were users of calcium channel blockers. In propensity score-weighted analyses, ACE-I/ARB users had marginally lower 30-day mortality than users of calcium channel blockers (13.9% versus 14.5%; RD, -0.6%; 95% CI, -1.0 to -0.1; RR, 0.96; 95% CI, 0.93-0.99), and a lower risk of admission to the intensive care unit (8.0% versus 9.6%; RD, -1.6%; 95% CI, -2.0 to -1.2; RR, 0.83; 95% CI, 0.80-0.87). Compared with nonusers, current ACE-I/ARB users had lower mortality (RD, -2.4%; 95% CI, -2.8 to -2.0; RR, 0.85; 95% CI, 0.83-0.87), but similar risk of admission to the intensive care unit (RD, 0.4%; 95% CI, 0.0-0.7; RR, 1.04; 95% CI, 1.00-1.09). Conclusions Among patients with influenza or pneumonia, ACE-I/ARB users had no increased risk of admission to the intensive care unit and slightly reduced mortality after controlling for confounding.

Keywords: angiotensin receptor blockers; angiotensin‐converting enzyme inhibitor; cohort study; infectious disease; intensive care unit.

PubMed Disclaimer

Conflict of interest statement

Dr Christiansen, Dr Heide‐Jørgensen, Dr Rasmussen, Dr Thomsen, and Dr Sørensen have not received any personal fees, grants, travel grants, or teaching grants from companies, but the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to (and administered by) Aarhus University. None of these studies are related to the current study. Dr Reilev, Dr Lund, Dr Pottegård, and Dr Hallas have participated in industry‐funded projects with money paid to their employer, University of Southern Denmark. None have received personal compensation of any kind, and none of these projects is related to the current study. The remaining authors have no disclosures to report.

Figures

Figure 1
Figure 1. Patient flow diagram.
ACE‐I indicates angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; and CCB, calcium channel blocker.
Figure 2
Figure 2. Crude (A) and propensity score‐weighted (B) 30‐day cumulative incidence (risk) and relative risk (RR) of death and intensive care unit (ICU) admission in patients with influenza or pneumonia, with only influenza, and with pneumonia with bacterial or unspecified pathogen.
ACEI indicates angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker.
Figure 3
Figure 3. Thirty‐day mortality and risk of intensive care unit (ICU) admission by different exposure definitions and subgroups.
ACE‐I indicates angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; and CCB, calcium channel blocker.
See this image and copyright information in PMC

References

    1. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID‐19): a review. JAMA. 2020;1824–1836. - PubMed
    1. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID‐19 infection? Lancet Respir Med. 2020;9:e21. - PMC - PubMed
    1. Sommerstein R, Gräni C. Rapid response: Re: preventing a covid‐19 pandemic: ACE inhibitors as a potential risk factor for fatal Covid‐19. BMJ. 2020;m810 Website name: . Available at: bmj.com https://www.bmj.com/conte​nt/368/bmj.M810/rr-2. Accessed August 14, 2020. - PubMed
    1. Patel AB, Verma A. COVID‐19 and angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers: what is the evidence? JAMA. 2020;1769–1770. - PubMed
    1. Hoffmann M, Kleine‐Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, et al. SARS‐CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;271–280.e8. - PMC - PubMed

Publication types

MeSH terms

Substances