Losartan fails to reduce lung injury in patients hospitalized with COVID-19

Losartan failed to reduce lung injury or improve clinical outcomes in patients hospitalized with COVID-19, researchers reported in JAMA Network Open.

“Even though this particular drug was not effective for the treatment of COVID-19, repurposing inexpensive and relatively safe medications remains an important approach to contain health care costs,” Michael A. Puskarich, MD, MS, associate professor in emergency medicine at University of Minnesota Medical School and emergency physician at Hennepin Healthcare, Minneapolis, said in a related press release. “Finding effective treatments for COVID-19 that can be widely used across both the developed and developing world remains an important ongoing area of investigation.”

Researchers conducted the multicenter, masked, placebo-controlled, randomized clinical Angiotensin Receptor Blocker Based Lung Protective Strategies for Inpatients with COVID-19 (ALPS-IP) trial at 13 U.S. hospitals from April 2020 to February 2021. The trial enrolled 205 patients hospitalized with COVID-19 (mean age, 55.2 years; 60% men) with a respiratory sequential organ failure assessment score of at least 1 who were not already using renin-angiotensin-aldosterone system inhibitors. Patients were randomly assigned to receive oral losartan 50 mg twice daily (n = 101) or placebo (n = 104) for 10 days or until discharge.

The primary outcome was arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2:FiO2) ratio at 7 days. Secondary outcomes included COVID-19 severity, days without supplemental oxygen ventilation or vasopressors and 28-day mortality.

Researchers observed no significant effect of losartan treatment on PaO2:FiO2 ratio at 7 days (difference, –24.8; 95% CI, –55.6 to 6.1; P = .12) compared with placebo. In addition, losartan did not improve COVID-19 severity, days without supplemental oxygen ventilation at 28 days (losartan, 18.1 vs. placebo, 18.4) or mortality at 28 days (losartan, 11 vs. placebo, 9).

Patients assigned losartan had fewer vasopressor-free days compared with patients assigned placebo (median, 8.7 days vs. 9.4 days; P = .04).

“It is important to note that we observed two potentially harmful effects of losartan on hemodynamics and kidney function,” the researchers wrote. “However, a higher proportion of participants in the intervention group were enrolled in the ICU, indicating potential small imbalances in severity of illness at enrollment. Generally, patients requiring the ICU are characterized by older age, are more likely to be a race other than white and to be men, and have comorbidities. These patients may be more likely to exhibit cytokine storm related to inflammaging or baseline metabolic syndrome, although these factors were well matched by randomization, making them more likely to contribute to initial disposition.”

Losartan was investigated based on early reports that suggested benefit in preclinical models of the 2003 SARS virus, according to the release.

The researchers noted in the release that more studies of protein and cellular signaling from ALPS-COVID trial participants are ongoing.

“We hope that future study findings of these proteins may show insights into why the body responds the way it does to COVID-19,” Christopher J. Tignanelli, MD, MS, assistant professor in surgery at the University of Minnesota Medical School, Minneapolis, said in the release. “Critically, this will help us understand why some people develop severe disease following COVID-19 infection and others are asymptomatic.”

Reference:

• U of M researchers find that losartan is not effective in reducing COVID-19 lung injuries. Published March 16, 2022. Accessed March 17, 2022.