tetano
Editor, Senior Moderator
Clin Infect Dis
. 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[SUP] 1 [/SUP], Pierre Asfar[SUP] 2 [/SUP], Matthew Cheng[SUP] 3 [/SUP], Julien Demiselle[SUP] 4 [/SUP], Joel Singer[SUP] 5 [/SUP], Terry Lee[SUP] 5 [/SUP], David Sweet[SUP] 1 [/SUP], John Boyd[SUP] 6 [/SUP], Keith Walley[SUP] 6 [/SUP], Greg Haljan[SUP] 7 [/SUP], Omar Sharif[SUP] 7 [/SUP], Guillaume Geri[SUP] 8 [/SUP], Johann Auchabie[SUP] 9 [/SUP], Jean-Pierre Quenot[SUP] 10 [/SUP], Todd C Lee[SUP] 11 [/SUP], Jennifer Tsang[SUP] 12 [/SUP], Ferhat Meziani[SUP] 13 [/SUP], Francois Lamontagne[SUP] 14 [/SUP], Vincent Dubee[SUP] 15 [/SUP], Sigismond Lasocki[SUP] 16 [/SUP], Daniel Ovakim[SUP] 17 [/SUP], Gordon Wood[SUP] 17 [/SUP], Alexis Turgeon[SUP] 18 [/SUP], Yves Cohen[SUP] 19 [/SUP], Eddy Lebas[SUP] 20 [/SUP], Marine Goudelin[SUP] 21 [/SUP], David Forrest[SUP] 22 [/SUP], Alastair Teale[SUP] 22 [/SUP], Jean-Paul Mira[SUP] 23 [/SUP], Robert Fowler[SUP] 24 [/SUP], Nick Daneman[SUP] 24 [/SUP], Neill K J Adhikari[SUP] 24 [/SUP], Marie Gousseff[SUP] 25 [/SUP], Pierre Leroy[SUP] 26 [/SUP], Gaetan Plantefeve[SUP] 27 [/SUP], Patrick Rispal[SUP] 28 [/SUP], Roxane Courtois[SUP] 29 [/SUP], Brent Winston[SUP] 30 [/SUP], Steve Reynolds[SUP] 31 32 [/SUP], Peter Birks[SUP] 31 32 [/SUP], Boris Bienvenu[SUP] 33 [/SUP], Jean-Marc Tadie[SUP] 34 [/SUP], Jean-Philippe Talarmin[SUP] 35 [/SUP], Severine Ansart[SUP] 36 [/SUP], James A Russell[SUP] 6 [/SUP]; ARBs CORONA II Team
Collaborators, Affiliations
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.
. 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[SUP] 1 [/SUP], Pierre Asfar[SUP] 2 [/SUP], Matthew Cheng[SUP] 3 [/SUP], Julien Demiselle[SUP] 4 [/SUP], Joel Singer[SUP] 5 [/SUP], Terry Lee[SUP] 5 [/SUP], David Sweet[SUP] 1 [/SUP], John Boyd[SUP] 6 [/SUP], Keith Walley[SUP] 6 [/SUP], Greg Haljan[SUP] 7 [/SUP], Omar Sharif[SUP] 7 [/SUP], Guillaume Geri[SUP] 8 [/SUP], Johann Auchabie[SUP] 9 [/SUP], Jean-Pierre Quenot[SUP] 10 [/SUP], Todd C Lee[SUP] 11 [/SUP], Jennifer Tsang[SUP] 12 [/SUP], Ferhat Meziani[SUP] 13 [/SUP], Francois Lamontagne[SUP] 14 [/SUP], Vincent Dubee[SUP] 15 [/SUP], Sigismond Lasocki[SUP] 16 [/SUP], Daniel Ovakim[SUP] 17 [/SUP], Gordon Wood[SUP] 17 [/SUP], Alexis Turgeon[SUP] 18 [/SUP], Yves Cohen[SUP] 19 [/SUP], Eddy Lebas[SUP] 20 [/SUP], Marine Goudelin[SUP] 21 [/SUP], David Forrest[SUP] 22 [/SUP], Alastair Teale[SUP] 22 [/SUP], Jean-Paul Mira[SUP] 23 [/SUP], Robert Fowler[SUP] 24 [/SUP], Nick Daneman[SUP] 24 [/SUP], Neill K J Adhikari[SUP] 24 [/SUP], Marie Gousseff[SUP] 25 [/SUP], Pierre Leroy[SUP] 26 [/SUP], Gaetan Plantefeve[SUP] 27 [/SUP], Patrick Rispal[SUP] 28 [/SUP], Roxane Courtois[SUP] 29 [/SUP], Brent Winston[SUP] 30 [/SUP], Steve Reynolds[SUP] 31 32 [/SUP], Peter Birks[SUP] 31 32 [/SUP], Boris Bienvenu[SUP] 33 [/SUP], Jean-Marc Tadie[SUP] 34 [/SUP], Jean-Philippe Talarmin[SUP] 35 [/SUP], Severine Ansart[SUP] 36 [/SUP], James A Russell[SUP] 6 [/SUP]; ARBs CORONA II Team
Collaborators, Affiliations
- PMID: 39325643
- DOI: 10.1093/cid/ciae306
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.