In a groundbreaking development, the SAXOPHONE study indicates that apixaban is a secure choice for pediatric patients grappling with various congenital or acquired heart diseases necessitating chronic anticoagulation for thromboprophylaxis. The study, led by Dr. R. Mark Payne from the Indiana University School of Medicine in Indianapolis, highlights low overall bleeding rates after a year of treatment with apixaban (Eliquis; Bristol Myers Squibb) compared to standard-of-care anticoagulation with warfarin or low-molecular-weight heparin. The research findings are set to be published online ahead of the December 12, 2023, issue of the Journal of the American College of Cardiology.
The demand for a less cumbersome approach to providing chronic anticoagulation to children with heart disease has been long-standing, emphasized Payne. While warfarin and low-molecular-weight heparin are effective, they come with various drawbacks, such as the aversion to heparin injections by parents, leading to a preference for oral medications like warfarin. However, the latter requires frequent blood tests and imposes potential restrictions on children’s diets and activities.
“It makes it burdensome and sometimes very erratic to put children on the current standard-of-care anticoagulation,” Payne explained.
Direct oral anticoagulants (DOACs), including apixaban, have emerged as a potential solution, addressing some of the challenges posed by warfarin and heparin. Previous studies have suggested the safety and efficacy of DOACs in adults, paving the way for exploring their use in the pediatric population. The SAXOPHONE trial, a phase II, open-label study conducted at 33 centers across 12 countries, randomized 192 patients aged 28 days to less than 18 years with congenital or acquired heart disease requiring chronic thromboprophylaxis.
The primary endpoint of the trial, adjudicated major or clinically relevant nonmajor bleeding, showed a nonsignificant difference between apixaban and standard-of-care anticoagulation (0.8% vs. 4.8%). Although the rate of any bleeding was higher in the apixaban arm, the study underscores the safety and predictability of apixaban’s weight-based dosing. The researchers suggest that apixaban could serve as a safe and convenient alternative to current standard-of-care anticoagulants for thromboprophylaxis in children with heart disease.
In an accompanying editorial, Dr. Craig Mullen from the University of Rochester, NY, commended the study for providing crucial data on the pharmacokinetics and pharmacodynamics of apixaban in children. He acknowledged that while DOACs address some issues with warfarin and heparin, they come with bleeding risks and potential drug-drug interactions.
Despite the promising results, Mullen highlighted practical challenges, such as the availability of lower-dose capsules and the higher cost of apixaban, which may impact its cost-effectiveness. Nonetheless, he lauded the investigators for their work, providing valuable information for pediatric cardiologists and hematologists.
Dr. Payne emphasized that while there are specific scenarios where standard options may still be preferred, apixaban could potentially replace warfarin in many cases, offering a safer alternative for pediatric patients with heart disease. However, he cautioned that the results do not apply to patients with an established thrombus, where warfarin or low-molecular-weight heparin should still be considered the preferred options.
