Efficacy of Losartan in Hospitalized Patients With COVID-19–Induced Lung Injury

Abstract

IMPORTANCE SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. OBJECTIVE To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. INTERVENTIONS Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. MAIN OUTCOMES AND MEASURES The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 :FiO 2 ) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental O 2 , ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensinconverting enzymes 1 and 2)] were measured in a subgroup of participants. RESULTS A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo.Compared with placebo, losartan did not significantly affect PaO 2 :FiO 2 ratio at 7 days (difference, −24.8 [95%, −55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). CONCLUSIONS AND RELEVANCEThis randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve PaO 2 :FiO 2 ratio at 7 days. These data may have implications for ongoing clinical trials.

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“…How beneficial are ACE2-modulating medications, such as ACE inhibitors or ang II receptor blockers (ARBs)? Recent clinical study ( 173 ) suggested that oral administration of 50-mg losartan, an ARB, for 10 days did not improve arterial partial pressure of oxygen to fraction of inspired oxygen ( : ) ratio in the hospitalized patients with COVID-19 and acute lung injury. Further studies are needed with large cohort studies under acute as well as chronic conditions to understand further details.…”

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