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
Randomized Controlled Trial
. 2024 Sep 26;79(3):615-625.
doi: 10.1093/cid/ciae306.

Effects of Losartan on Patients Hospitalized for Acute COVID-19: A Randomized Controlled Trial

Karen C Tran  1 , Pierre Asfar  2 , Matthew Cheng  3 , Julien Demiselle  4 , Joel Singer  5 , Terry Lee  5 , David Sweet  1 , John Boyd  6 , Keith Walley  6 , Greg Haljan  7 , Omar Sharif  7 , Guillaume Geri  8 , Johann Auchabie  9 , Jean-Pierre Quenot  10 , Todd C Lee  11 , Jennifer Tsang  12 , Ferhat Meziani  13 , Francois Lamontagne  14 , Vincent Dubee  15 , Sigismond Lasocki  16 , Daniel Ovakim  17 , Gordon Wood  17 , Alexis Turgeon  18 , Yves Cohen  19 , Eddy Lebas  20 , Marine Goudelin  21 , David Forrest  22 , Alastair Teale  22 , Jean-Paul Mira  23 , Robert Fowler  24 , Nick Daneman  24 , Neill K J Adhikari  24 , Marie Gousseff  25 , Pierre Leroy  26 , Gaetan Plantefeve  27 , Patrick Rispal  28 , Roxane Courtois  29 , Brent Winston  30 , Steve Reynolds  31   32 , Peter Birks  31   32 , Boris Bienvenu  33 , Jean-Marc Tadie  34 , Jean-Philippe Talarmin  35 , Severine Ansart  36 , James A Russell  6 ; ARBs CORONA II Team
Collaborators, Affiliations
Randomized Controlled Trial

Effects of Losartan on Patients Hospitalized for Acute COVID-19: A Randomized Controlled Trial

Karen C Tran et al. Clin Infect Dis. .

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19.

Methods: Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25-100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs).

Results: The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 [95% confidence interval, .47-2.64]; P = .81), nor did organ dysfunction or secondary outcomes.

Conclusions: Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19.

Clinical trials registration: NCT04606563.

Keywords: COVID-19; angiotensin receptor blocker; losartan; mortality.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest . J. A. R. reports patents owned by the University of British Columbia that are related to (i) the use of PCSK9 inhibitor(s) in sepsis, (ii) the use of vasopressin in septic shock, and (iii) a patent owned by Ferring for use of selepressin in septic shock; J. A. R. is an inventor on these patents. J. A. R. was a founder, director, and shareholder in Cyon Therapeutics Inc (now closed) and is a shareholder in Molecular You Corp; is the Senior Research Advisor of the British Columbia, Canada Post COVID–Interdisciplinary Clinical Care Network (PC-ICCN); reports receiving consulting fees in the last 3 years as a funded member of the data and safety monitoring board of a National Institutes of Health–sponsored trial of plasma in COVID-19 (PASS-IT-ON; 2020–2021); has received grants for COVID-19 and for pneumonia research from CIHR and the St Paul's Foundation; and was a nonfunded science advisor and member of the government of Canada COVID-19 Therapeutics Task Force (June 2020–2021). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Study flow diagram of the ARBs CORONA II trial of losartan versus usual care in patients hospitalized for acute coronavirus disease 2019, including inclusions, exclusions, reasons for exclusions, and final numbers included in the treatment and control groups. *see supplement for list of sites. Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; COVID-19, coronavirus disease 2019; DNR, do not resuscitate.
Figure 2.
Figure 2.
Kaplan-Meier curves for time to death of patients (all patients, those not in intensive care unit [ICU], and those in ICU on day of admission to study) of the ARBs CORONA II trial of losartan versus usual care in patients hospitalized for acute coronavirus disease 2019. There were no differences in time to death overall or in ICU-admitted versus not ICU-admitted subgroups. Abbreviations: CI, confidence interval; HR, hazard ratio; ICU, intensive care unit.
See this image and copyright information in PMC

References

    1. RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. . Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021; 384:693–704. - PMC - PubMed
    1. ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, et al. . Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N Engl J Med 2021; 385:790–802. - PMC - PubMed
    1. RECOVERY Collaborative Group . Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397:1637–45. - PMC - PubMed
    1. Kalil AC, Patterson TF, Mehta AK, et al. . Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med 2021; 384:795–807. - PMC - PubMed
    1. Hoffmann M, Kleine-Weber H, Schroeder S, et al. . SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181:271–80.e8. - PMC - PubMed

Publication types

MeSH terms

Substances

Associated data

Grants and funding