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

Autor:	Tran KC; Division of General Internal Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, Canada., Asfar P; Service de Médecine Intensive-Réanimation, Centre Hospitalier Universitaire d'Angers, Angers, France., Cheng M; McGill's Interdisciplinary Initiative in Infection and Immunity, Divisions of Infectious Diseases and Medical Microbiology, McGill University Health Centre, Montreal, Quebec, Canada., Demiselle J; Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Singer J; Centre for Health Evaluation and Outcome Science, St Paul's Hospital and University of British Columbia, Vancouver, Canada., Lee T; Centre for Health Evaluation and Outcome Science, St Paul's Hospital and University of British Columbia, Vancouver, Canada., Sweet D; Division of General Internal Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, Canada., Boyd J; Division of Critical Care Medicine, and Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, Canada., Walley K; Division of Critical Care Medicine, and Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, Canada., Haljan G; Department of Medicine and Critical Care Medicine, Surrey Memorial Hospital, British Columbia, Canada., Sharif O; Department of Medicine and Critical Care Medicine, Surrey Memorial Hospital, British Columbia, Canada., Geri G; Service de Médecine Intensive-Réanimation, Assistance Publique-Hôpitaux de Paris Ambroise Paré, Boulogne, France., Auchabie J; Service de Réanimation Polyvalente, Centre Hospitalier de Cholet., Quenot JP; Service de Médecine Intensive-Réanimation, Centre Hospitalier Universitaire Dijon, Dijon, France., Lee TC; McGill's Interdisciplinary Initiative in Infection and Immunity, McGill University Health Centre, Montreal, Quebec, Canada., Tsang J; Niagara Health, McMaster University, St Catherines, Ontario, Canada., Meziani F; Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil Strasbourg, Strasbourg, France., Lamontagne F; Centre Hospitalier Universitaire de Sherbrooke, University of Sherbrooke, Quebec, Canada., Dubee V; Service de Maladies Infectieuses, Centre Hospitalier Universitaire d'Angers, Angers, France., Lasocki S; Service de Réanimation Chirurgicale, Centre Hospitalier Universitaire Angers, Angers, France., Ovakim D; Royal Jubilee Hospital, Island Health, Victoria, British Columbia., Wood G; Royal Jubilee Hospital, Island Health, Victoria, British Columbia., Turgeon A; Department of Medicine, Centre Hospitalier Universitaire de Québec-Université Laval, Quebec, Canada., Cohen Y; Service de Médecine Intensive-Réanimation, Assistance Publique-Hôpitaux de Paris Avicenne, Bobigny, France., Lebas E; Service de Réanimation Polyvalente, Centre Hospitalier Bretagne-Atlantique, Vannes, France., Goudelin M; Service de Réanimation Polyvalente, Centre Hospitalier Universitaire Limoges, Limoges, France., Forrest D; Department of Medicine, Nanaimo Regional General Hospital, British Columbia, Canada., Teale A; Department of Medicine, Nanaimo Regional General Hospital, British Columbia, Canada., Mira JP; Service de Médecine Intensive-Réanimation, Assistance Publique-Hôpitaux de Paris, Cochin, France., Fowler R; Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Daneman N; Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Adhikari NKJ; Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Gousseff M; Service de Médecine Interne-Maladies Infectieuses-Hématologie, Centre Hospitalier Bretagne-Atlantique, Vannes, France., Leroy P; Service de médecine polyvalente et maladies infectieuses, Centre Hospitalier Melun, Melun, France., Plantefeve G; Service de Réanimation Polyvalente, Centre Hospitalier Argenteuil, France., Rispal P; Department of Medicine, Service de médecine interne, Centre Hospitalier Agen, Agen, France., Courtois R; Service de Médecine post-urgences-Maladies infectieuses, Centre Hospitalier de Cholet, Cholet, France., Winston B; Departments of Critical Care Medicine, Medicine, and Biochemistry and Molecular Biology, Foothills Medical Centre, University of Calgary, Alberta, Canada., Reynolds S; Critical Care Medicine, Royal Columbian Hospital, New Westminster, British Columbia, Canada.; Department of Medicine, Simon Fraser University, Surrey, British Columbia, Canada., Birks P; Critical Care Medicine, Royal Columbian Hospital, New Westminster, British Columbia, Canada.; Department of Medicine, Simon Fraser University, Surrey, British Columbia, Canada., Bienvenu B; Service de médecine interne, Hôpital St Joseph, Marseille, France., Tadie JM; Service de Médecine Intensive-Réanimation et de Maladies Infectieuses, Centre Hospitalier Universitaire de Rennes, Rennes, France., Talarmin JP; Service de médecine interne, maladies du sang et infectiologie, Centre Hospitalier de Quimper, Quimper, France., Ansart S; Service de Maladies Infectieuses, Centre Hospitalier Régional Universitaire Brest, Brest, France., Russell JA; Division of Critical Care Medicine, and Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, Canada.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Sep 26; Vol. 79 (3), pp. 615-625.
DOI:	10.1093/cid/ciae306
Abstrakt:	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. Competing Interests: 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. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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