Effects of Losartan on Patients Hospitalized for Acute COVID-19: A Randomized Controlled Trial
Authors: Tran Karen C , Asfar Pierre , Cheng Matthew , Demiselle Julien , Singer Joel , Lee Terry , Sweet David , Boyd John , Walley Keith , Haljan Greg , Sharif Omar , Geri Guillaume , Auchabie Johann , Quenot Jean-Pierre , Lee Todd C , Tsang Jennifer , Meziani Ferhat , Lamontagne Francois , Dubee Vincent , Lasocki Sigismond , Ovakim Daniel , Wood Gordon , Turgeon Alexis , Cohen Yves , Lebas Eddy , Goudelin Marine , Forrest David , Teale Alastair , Mira Jean-Paul , Fowler Robert , Daneman Nick , Adhikari Neill K J , Gousseff Marie , Leroy Pierre , Plantefeve Gaetan , Rispal Patrick , Courtois Roxane , Winston Brent , Reynolds Steve , Birks Peter , Bienvenu Boris , Tadie Jean-Marc , Talarmin Jean-Philippe , Ansart Severine , Russell James A ,   for the ARBs CORONA II Team, 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 
Published: July 2024

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 &lt; .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.