Effects of Losartan on Patients Hospitalized for Acute Coronavirus Disease 2019: A Randomized Controlled Trial-Reference-Cited by-同舟云学术

Effects of Losartan on Patients Hospitalized for Acute Coronavirus Disease 2019: A Randomized Controlled Trial

Published:2024-07-10 Issue: Volume: Page:
ISSN:1058-4838
Container-title:Clinical Infectious Diseases
language:en
Short-container-title:

Author:

Tran Karen C¹,Asfar Pierre²,Cheng Matthew³,Demiselle Julien⁴,Singer Joel⁵,Lee Terry⁵,Sweet David¹,Boyd John⁶,Walley Keith⁶,Haljan Greg⁷,Sharif Omar⁷,Geri Guillaume⁸,Auchabie Johann⁹,Quenot Jean-Pierre¹⁰,Lee Todd C¹¹,Tsang Jennifer¹²,Meziani Ferhat¹³,Lamontagne Francois¹⁴,Dubee Vincent¹⁵,Lasocki Sigismond¹⁶,Ovakim Daniel¹⁷,Wood Gordon¹⁷,Turgeon Alexis¹⁸,Cohen Yves¹⁹,Lebas Eddy²⁰,Goudelin Marine²¹,Forrest David²²,Teale Alastair²²,Mira Jean-Paul²³,Fowler Robert²⁴,Daneman Nick²⁴,Adhikari Neill K J²⁴,Gousseff Marie²⁵,Leroy Pierre²⁶,Plantefeve Gaetan²⁷,Rispal Patrick²⁸,Courtois Roxane²⁹,Winston Brent³⁰,Reynolds Steve³¹³²,Birks Peter³¹³²,Bienvenu Boris³³,Tadie Jean-Marc³⁴,Talarmin Jean-Philippe³⁵,Ansart Severine³⁶,Russell James A⁶, ,Russell J,Tran K,Cheng M,Asfar P,Demiselle J,Singer J,Mann P,Jain F,Tran K,Donohoe K,Leung V,Lee T,Tran K,Boyd J,Walley K,Tran K,Sweet D,Haljan G,Sharif O,Ovakim D,Wood G,Forrest D,Teale A,Reynolds S,Birk P,Winston B,Fowler R,Dameman N,Adhikari N,Tsang J,Cheng M,Lamontagne F,Turgeon-Fournier A,Asfar ,Demiselle ,Geri D G,Auchabie J,Quenot J P,Meziani F,Dubee V,Lasocki S,Cohen Y,Lebas E,Goudelin M,Mira J P,Gousseff M,Leroy P,Plantefev G,Rispal P,Courtois R,Bievenue B,Tadie J M,Talarmin J P,Ansart S,Yi Tae Won,Levin Adeera

Affiliation:

1. Division of General Internal Medicine, Vancouver General Hospital, University of British Columbia , Vancouver , Canada

2. Service de Médecine Intensive-Réanimation, Centre Hospitalier Universitaire d’Angers , Angers , France

3. McGill’s Interdisciplinary Initiative in Infection and Immunity, Divisions of Infectious Diseases and Medical Microbiology, McGill University Health Centre , Montreal, Quebec , Canada

4. Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg , Strasbourg , France

5. Centre for Health Evaluation and Outcome Science, St Paul's Hospital and University of British Columbia , Vancouver , Canada

6. Division of Critical Care Medicine, and Centre for Heart Lung Innovation, St Paul's Hospital , Vancouver , Canada

7. Department of Medicine and Critical Care Medicine, Surrey Memorial Hospital , British Columbia , Canada

8. Service de Médecine Intensive-Réanimation, Assistance Publique–Hôpitaux de Paris Ambroise Paré , Boulogne , France

9. Service de Réanimation Polyvalente, Centre Hospitalier de Cholet

10. Service de Médecine Intensive-Réanimation, Centre Hospitalier Universitaire Dijon , Dijon , France

11. McGill's Interdisciplinary Initiative in Infection and Immunity, McGill University Health Centre , Montreal, Quebec , Canada

12. Niagara Health, McMaster University , St Catherines, Ontario , Canada

13. Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil Strasbourg , Strasbourg , France

14. Centre Hospitalier Universitaire de Sherbrooke, University of Sherbrooke , Quebec , Canada

15. Service de Maladies Infectieuses, Centre Hospitalier Universitaire d'Angers , Angers , France

16. Service de Réanimation Chirurgicale, Centre Hospitalier Universitaire Angers , Angers , France

17. Royal Jubilee Hospital, Island Health , Victoria, British Columbia

18. Department of Medicine, Centre Hospitalier Universitaire de Québec–Université Laval , Quebec , Canada

19. Service de Médecine Intensive-Réanimation, Assistance Publique–Hôpitaux de Paris Avicenne , Bobigny , France

20. Service de Réanimation Polyvalente, Centre Hospitalier Bretagne-Atlantique , Vannes , France

21. Service de Réanimation Polyvalente, Centre Hospitalier Universitaire Limoges , Limoges , France

22. Department of Medicine, Nanaimo Regional General Hospital , British Columbia , Canada

23. Service de Médecine Intensive-Réanimation, Assistance Publique-Hôpitaux de Paris , Cochin , France

24. Critical Care Medicine, Sunnybrook Health Sciences Centre , Toronto, Ontario , Canada

25. Service de Médecine Interne–Maladies Infectieuses–Hématologie, Centre Hospitalier Bretagne-Atlantique , Vannes , France

26. Service de médecine polyvalente et maladies infectieuses, Centre Hospitalier Melun , Melun , France

27. Service de Réanimation Polyvalente, Centre Hospitalier Argenteuil , France

28. Department of Medicine, Service de médecine interne, Centre Hospitalier Agen , Agen , France

29. Service de Médecine post-urgences–Maladies infectieuses, Centre Hospitalier de Cholet , Cholet , France

30. Departments of Critical Care Medicine, Medicine, and Biochemistry and Molecular Biology, Foothills Medical Centre, University of Calgary , Alberta , Canada

31. Critical Care Medicine, Royal Columbian Hospital , New Westminster, British Columbia , Canada

32. Department of Medicine, Simon Fraser University , Surrey, British Columbia , Canada

33. Service de médecine interne, Hôpital St Joseph , Marseille , France

34. Service de Médecine Intensive-Réanimation et de Maladies Infectieuses, Centre Hospitalier Universitaire de Rennes , Rennes , France

35. Service de médecine interne, maladies du sang et infectiologie, Centre Hospitalier de Quimper , Quimper , France

36. Service de Maladies Infectieuses, Centre Hospitalier Régional Universitaire Brest , Brest , France

Abstract

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.

Funder

Canadian Institutes of Health Research

Publisher

Oxford University Press (OUP)

Link

https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciae306/58447468/ciae306.pdf

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