Inpatient Insights

Tenecteplase shows promise for treatment of acute stroke

Thrombolysis for acute ischemic stroke significantly improves independent recovery when administered within 4.5 hours of symptom onset. The standard thrombolytic agent for many years has been alteplase, but recent research has shown that tenecteplase may have potential benefits over alteplase because it is administered as a single bolus rather than the alteplase regimen of a bolus followed by 1 hour of maintenance infusion. The ATTEST-2 investigators conducted a prospective, randomized, parallel-group, open-label trial with masked endpoint evaluation in 39 stroke centers in the United Kingdom to determine whether tenecteplase was noninferior or superior to alteplase within 4.5 hours of onset.

The study, published in the November 2024 issue of The Lancet Neurology, included almost 2,000 patients with acute ischemic stroke between January 25, 2017, and May 30, 2023, who were randomly assigned 1:1 to receive I.V. alteplase 0.9 mg/kg or tenecteplase 0.25 mg/kg. Tenecteplase was shown to be noninferior to alteplase within 4.5 hours of symptom onset in acute ischemic stroke, with similar occurrence of mortality, symptomatic intracerebral hemorrhage, parenchymal hematoma type 2, post-treatment intracranial bleed, significant extracranial hemorrhage, and angioedema in both groups.

The researchers concluded that the available trial evidence and easier administration of tenecteplase, especially in the context of interhospital transfers, suggests that tenecteplase should be preferred to alteplase for thrombolysis in acute ischemic stroke. They suggested that future research should investigate the safety and efficacy of tenecteplase in later time windows and in patients with unknown onset. ■

Use of glucocorticoids in adults hospitalized with CAP outside of the ICU

Little is known about the real-world use of systemic glucocorticoids to treat patients hospitalized with community-acquired pneumonia (CAP) outside of the ICU. Researchers from St. Michael’s Hospital (Toronto) conducted a retrospective cohort study including almost 12,000 patients hospitalized for CAP without chronic pulmonary disease at seven hospitals in Ontario, Canada, to investigate the association between glucocorticoid prescriptions and clinical outcomes, using propensity score overlap weighting to account for confounding by indication.

Results of the study, published in the November 2024 issue of the Journal of Hospital Medicine, showed that glucocorticoids were prescribed in 11.1% of the patients, increasing over time from 10% in 2010 to 11.9% in 2020. Physician glucocorticoid prescribing ranged from 2.9% to 34.6%, and patients receiving glucocorticoids tended to be younger, have higher Charlson comorbidity scores, more cancer occurrences, more renal disease, and less dementia. Patients treated with glucocorticoids had higher rates of in-hospital mortality, but glucocorticoid use was not associated with ICU admission, length of hospital stay, or 30-day readmission.

The authors concluded that while glucocorticoid use was associated with greater in-hospital mortality, their findings are limited by large selection effects. They recommended that clinicians exercise caution in prescribing glucocorticoids for nonsevere CAP and that definitive trials should be conducted for this population.  ■

Are GLP-1 agonists effective at treating alcohol use disorder?

GLP-1 agonists have been approved for clinical use to treat diabetes and obesity, and preclinical studies in rodents and monkeys, as well as human case reports, have shown that GLP-1 agonists can also reduce alcohol consumption. Because a genetic variation in GLP-1R has been shown to be associated with increased risk of alcohol use disorder, a group of researchers in Finland and Sweden conducted a study, published online in JAMA Psychiatry on November 13, 2024, to determine whether the risk of hospitalization due to alcohol use disorder is decreased during the use of GLP-1 agonists compared with periods of nonuse for the same individual.

The observational cohort study was conducted nationwide in Sweden using data from January 2006 to December 2023. The population-based cohort was identified from registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. All residents aged 16 to 64 years who had a diagnosis of alcohol use disorder were included in the study. Of the almost 228,000 individuals with alcohol use disorder, approximately 133,000 individuals were hospitalized for alcohol use disorder. Use of semaglutide (4,321 users) was associated with the lowest risk and use of liraglutide (2,509 users) with the second lowest risk of hospitalization for both alcohol use disorder and SUD.

The researchers concluded that GLP-1 agonists, especially semaglutide, offer promise as a novel treatment to reduce alcohol consumption and to prevent development of alcohol-related outcomes but that randomized clinical trials are needed to verify these initial findings. ■

Gabapentinoids may increase the risk of hip fracture

Gabapentinoids have been shown to be a safer alternative to opioids for the treatment of neuropathic pain, sparking an exponential increase in use, especially among older adults. A case-case-time-control study published in JAMA Network Open on November 13, 2024, investigated the relationship between gabapentinoid use and increased risk of hip fracture across age groups, frailty status, and history of chronic kidney disease. The study included patients hospitalized for hip fracture in Victoria, Australia, between March 1, 2013, and June 30, 2018, with at least one prescription for a gabapentinoid before fracture.

Of the more than 28,000 patients hospitalized for hip fractures, 3,190 patients were dispensed gabapentinoids before being admitted, with 94% of these using pregabalin. After excluding patients with incomplete data or who were hospitalized for more than 50% of the exposure ascertainment period, 2,644 patients were matched with at least one future case as a control. Results of the data analysis found that gabapentinoid dispensing was associated with higher odds of hip fracture and that patients had 30% increased risk of hip fracture within 60 days of gabapentinoid dispensing. The association was similar across age groups but higher in patients who were frail or had chronic kidney disease.

The authors concluded that in addition to the known risk associated with kidney disease, frailty status may be an important risk factor when considering use of gabapentinoids and suggest that frailty risk scores could be used to assess the risk of hip fracture before prescribing gabapentinoids. ■