Inpatient Insights
APhA Staff
Asundexian vs. apixaban in patients with AFib
The use of direct oral anticoagulants for stroke prevention in patients with AFib can cause a risk of bleeding and therefore limits their use. A recent study from the OCEANIC–AF Steering Committee investigated the efficacy of asundexian, an activated factor XI inhibitor that may prevent strokes with less bleeding. In the phase 3, international, double-blind trial, published in the January 2, 2025, issue of NEJM, almost 15,000 high-risk patients with AFib in 38 countries were assigned in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban. The primary efficacy objective was to determine whether asundexian is at least noninferior to apixaban for the prevention of stroke or systemic embolism. The primary safety objective was to determine whether asundexian is superior to apixaban with respect to major bleeding events.
Of the patients included in the study, 18.6% had chronic kidney disease, 18.2% had a previous stroke or transient ischemic attack, 16.8% had received oral anticoagulants for no more than 6 weeks, and the mean CHA2DS2–VASc score (range, 0 to 9, with higher scores indicating a greater risk of stroke) was 4.3. The trial was stopped early at the recommendation of the independent data monitoring committee when it was clear that stroke or systemic embolism occurred in more than three times as many patients in the asundexian group than in the apixaban group. However, the incidence of major bleeding events was lower among patients who received asundexian and the occurrence of adverse events was similar in the two groups.
Follow up was abbreviated because of the early trial conclusion, and the authors noted that whether asundexian is safe or effective in other populations (such as patients not at risk for both stroke and bleeding events or without an indication for indefinite use of oral anticoagulants) cannot be determined from their data. ■
Are SGLT-2 inhibitors safe for use with hospitalized patients?
SGLT-2 inhibitors are commonly used to control blood glucose by causing the kidneys to remove sugar from the body through the urine. They have also been determined to minimize the risk of kidney disease and CVD. However, the safety and efficacy of SGLT-2 inhibitors in hospitalized patients are unclear. In a study published in the December 2024 issue of Diabetes Care, researchers used data from the MEDLINE, Embase, Emcare, and Cochrane databases to evaluate outcomes of inpatient SGLT-2 inhibitor use.
Randomized controlled trials and observational cohort studies with assessment of SGLT-2 inhibitor use in patients hospitalized for any reason were included in the study. The researchers performed a random-effects meta-analysis of 23 trials that included almost 20,000 participants (29.5% with T2D) and compared use of SGLT-2 inhibitors with placebo or active comparator. Ketoacidosis rates were 0.210 per 100 person-years for patients receiving SGLT-2 inhibitors and 0.140 per 100 person-years for those receiving a placebo. The results indicated that SGLT-2 inhibitor use was associated with fewer readmissions and urgent visits and lower mortality rates in heart failure trials and lower incidence of acute kidney injury among all trials. Analysis of the 20 observational studies did not show increased adverse events.
The researchers concluded that SGLT-2 inhibitor use among hospitalized patients was associated with numerically higher rates of ketoacidosis, although further studies are required to confirm their analyses. ■
Does durvalumab improve outcomes for patients with liver cancer?
Transarterial chemoembolization (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolization. However, median progression-free survival is still approximately 7 months. The EMERALD-1 investigators conducted a multiregional, randomized, double-blind, placebo-controlled trial to assess whether adding durvalumab, with or without bevacizumab, would improve progression-free survival.
The phase 3 study included adults aged 18 years or older with unresectable liver cancer amenable to embolization, an Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable intrahepatic lesion at 157 medical sites in 18 countries. Eligible patients were randomly assigned (1:1:1), stratified by TACE method, region, and portal vein invasion, to TACE plus either durvalumab plus bevacizumab (1,500 mg I.V. durvalumab once every 4 weeks, then 1,120 mg durvalumab plus 15 mg/kg I.V. bevacizumab once every 3 weeks), durvalumab plus placebo (same regimen using placebo instead of bevacizumab), or placebo. The primary endpoint of the study, published in The Lancet on January 8, 2025, was progression-free survival.
As of data cutoff, median progression-free survival was 15.0 months with durvalumab plus bevacizumab, 10.0 months with durvalumab, and 8.2 months with placebo. The most common adverse events were hypertension in participants who received durvalumab and bevacizumab, anemia in participants who received durvalumab and placebo, and postembolization syndrome in participants who received placebo alone. Study treatment-related adverse events that led to death occurred in none of the 154 participants who received durvalumab and bevacizumab, 3 of 232 who received durvalumab and placebo, and 3 of 200 who received placebo alone. The researchers concluded that durvalumab plus bevacizumab plus TACE has the potential to set a new standard of care, and additional follow-up studies that include final overall survival data and patient-reported outcomes will help to further characterize the potential clinical benefits of this treatment. ■
Pharmacist-led management model improves medication adherence among patients with chronic heart failure
Poor medication adherence is associated with high morbidity and mortality among patients with chronic heart failure. A group of researchers in China conducted a randomized clinical trial involving 445 patients with chronic heart failure to investigate the efficacy of a pharmacist-led management intervention program compared with patients assigned to usual care.
The prospective, multicenter randomized clinical trial was conducted from March 2021 to May 2023 in the cardiology wards of five hospitals, with a follow-up duration of 52 weeks. Participants were 18 years or older, had a chronic heart failure diagnosis, and were receiving stable medication. They were randomly assigned to either the intervention group (pharmacist-led management) or the control group (usual care) in a 1:1 ratio. The intervention group received a multi
modal pharmaceutical intervention, including WeChat social media communication and education, and a standardized follow-up visit from a pharmacist every month. The control group received the standardized follow-up visit from nurses every month. The primary outcome was the proportion of days covered by heart failure medication at 52 weeks.
Results of the study, published in JAMA Network Open on December 20, 2024, showed that at 52 weeks, the intervention group had a significantly higher proportion of days covered for heart failure medication and a greater proportion of patients with a proportion of days covered of 80% or greater compared with the control group. The authors noted that no significant differences were observed between these groups in terms of clinical outcomes, including readmission rates, all-cause mortality, and adverse events. They suggested that future research should examine more comprehensive intervention strategies to identify the impact of pharmacists on the incidence and mortality of chronic heart failure. ■