Edoxaban better alternative vs. standard care for children at risk for blood clots
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CHICAGO — For children with rare heart conditions that increase risk for thromboembolism, daily edoxaban may be a safe and effective alternative compared with the current standard of care for this age group, researchers reported.
Edoxaban (Savaysa, Daiichi Sankyo) is FDA-approved for use in adults with atrial fibrillation and other conditions that increase risk for thromboembolism. Standard of care anticoagulation for thromboembolism in children with cardiac disease includes low-molecular-weight heparins or vitamin K antagonists that require frequent injections, blood tests and dietary adjustments. There are limited data comparing risk for major and clinically relevant bleeding with direct oral anticoagulants vs. conventional anticoagulants in children, Michael A. Portman, MD, FAHA, director of research in the division of cardiology at Seattle Children’s Hospital and professor in the department of pediatrics at the University of Washington School of Medicine, and colleagues wrote in an abstract.
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“DOACs have been used for many years in adults, but there have been few studies investigating DOACs in children,” Portman told Healio. “Specifically, there are no studies looking at children with cardiac disease who have a need for anti-clotting medication.”
Standard care treatment for children with cardiac disease is very difficult, Portman said. Most children who require anticoagulation would be prescribed warfarin, which has been used for decades but comes with drawbacks.
“The problem is you have to monitor warfarin with frequent blood testing; the time that children are in the therapeutic range with warfarin is very low, about 45% of the time, because warfarin is very unstable in children,” Portman said in an interview. “A lot of it is related to absorption, the type of diet a child might be on or if the child is taking antibiotics. The other medication used is enoxaparin, which requires two subcutaneous injections per day; many children find the injections painful and quality of life is substantially reduced.”
In an international prospective, open-label, randomized controlled trial, Portman and colleagues analyzed data from 168 children with cardiac disease randomly assigned 2:1 age- and weight-based oral edoxaban once-daily vs. standard of care treatment for 3 months from May 2018 through September 2021. Researchers stratified patients by concomitant use of aspirin and by underlying disease groups, including history of Fontan procedure; Kawasaki disease; HF; or other. The edoxaban groups continued the medication through a 1-year extension. The primary endpoint was adjudicated clinically relevant bleeding, defined by the International Society on Thrombosis and Haemostasis. The main secondary endpoint was a composite of symptomatic thromboembolism and asymptomatic intracardiac thrombosis.
The data were presented at the American Heart Association Scientific Sessions.
Researchers found that clinically relevant bleeding event rates were similar between groups during the main study period. One patient in each group experienced a nonmajor clinically relevant bleeding event.
Treatment-emergent adverse events occurred in 46.8% of children assigned edoxaban and in 41.4% of children who received standard of care.
One child in the standard-care group experienced two thromboembolism events.
Among 152 children continuing in the extension study, researchers observed one clinically relevant bleeding event (0.7%; trauma-related) and four thromboembolism events occurred (2.8%; two strokes and two coronary artery thromboses and/or MI).
Portman said edoxaban “may provide an advantage” for children compared with other options, considering difficulties with enoxaparin injections and food and drug interactions with warfarin.
“The results of the study show edoxaban was safe,” Portman told Healio. “The side effects of any anticoagulant are a bleed, but the clinically relevant bleeding events were extremely rare — in the standard care group there were two events and in edoxaban group, one event. As for efficacy, we could not conduct a statistical analysis, but again, events were rare and in the edoxaban group there were no thromboembolism events during the main study. It appears to be safe and effective, though we cannot say that with statistical certainty like we would in the adult studies. However, this is the best we are going to get in the pediatric population, as these conditions are rare.”
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Portman MA, et al. Abstract 316. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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