Advance care planning assessed, therapeutic heparin debated in recent COVID-19 articles

A study from one medical center analyzed the characteristics of patients who died of COVID-19 while hospitalized in 2020, particularly whether their deaths would have been expected soon without SARS-CoV2 infection. The results, published by the Journal of Hospital Medicine on March 16, included 243 patients ages 50 years and older (median age, 80 years; 40% female) who died in the hospital. Half of the patients were frail, and 41% had dementia. Clinician-researchers judged whether it would have been surprising for each patient to die within a year, if not for COVID-19, and concluded that 60% of the patients had advanced, serious illnesses that made their deaths not a surprise. In this group, 39% of patients were full code at admission, compared to 78.6% of those in whom death was not expected.

That rate of do-not-resuscitate orders is still too low, though, according to the study authors. “These findings suggest significant opportunities to improve end-of-life discussions and implement shared decision making tools regarding code status or goal concordant care, particularly in high-risk patients (such as those with dementia that are dependent on surrogate decision makers) early in (or even prior to) hospitalization events, during the COVID-19 pandemic,” they wrote. “We need to identify patients with a high likelihood of death early in the hospitalization and then initiate a goals of care discussion. During this discussion, we should focus on identifying preferences for care during the hospitalization, and should specifically ask about end-of-life care.”

The use of therapeutic heparin in acutely ill COVID-19 patients was debated in a pair of articles published by CHEST on March 16. The point and counterpoint review the findings and limitations of research on the topic, concluding with the authors' recommendations. “Available evidence from approximately 3,000 patients who were enrolled in [randomized controlled trials] that indicates a benefit of therapeutic heparin in acutely ill patients who were hospitalized with COVID-19 cannot be discounted by clinicians committed to the practice of evidence-based medicine,” said the article in favor. “As a whole, the best evidence to date suggests that therapeutic anticoagulation likely benefits some patients who are moderately ill with COVID-19, but the concerns listed earlier urge us to avoid blindly following the guidelines and instead to consider carefully the risks and benefits for each individual patient,” argued the counterpoint.

Losartan did not improve lung injury in COVID-19 inpatients, according to a randomized trial published by JAMA Network Open on March 16. The trial included 205 patients at 13 U.S. hospitals who had a respiratory sequential organ failure assessment score of at least 1 and were not already on a renin-angiotensin-aldosterone system inhibitor. They were randomized to oral losartan, 50 mg, twice daily (n=101) or placebo (n=104) for 10 days or until hospital discharge. Losartan did not improve the primary outcome of arterial partial pressure of oxygen to fraction of inspired oxygen ratio at seven days or secondary outcomes of COVID-19 severity; days without supplemental oxygen, ventilation, or vasopressors; and mortality. The study authors also noted indications of potentially harmful effects on hemodynamics and kidney function, leading them to conclude that “losartan treatment is not indicated in this setting.”

Another negative result came from a study of gimsilumab, an anti-granulocyte-macrophage colony-stimulating factor monoclonal antibody, published by the American Journal of Respiratory and Critical Care Medicine on March 15. A total of 225 hospitalized COVID-19 patients with elevated inflammatory markers and hypoxemia at 21 U.S. hospitals were randomized 1:1 to receive two doses of gimsilumab or placebo one week apart. At day 43, the groups did not show any significant difference in all-cause mortality (28.3% and 23.2%, respectively; P=0.377) or key secondary outcomes, leading to the early termination of the trial, which was designed, overseen, and funded by Kinevant Sciences.