Dr Michael Portman: Edoxaban Facilitates Easier Treatment, Improved QOL in Pediatric Cardiac Disease

As part of the T. Duckett Jones Memorial Lecture and Outstanding Research Awards in Pediatric Cardiology, at this year’s American Heart Association’s Scientific Sessions in Chicago, Michael A. Portman, MD, FAHA, director, Pediatric Cardiovascular Research, Center for Integrative Brain Research, and professor of pediatrics at Seattle Children's and the University of Washington in Seattle, today will present “Edoxaban for Pediatric Patients With Cardiac Diseases: A Randomized, Open Label, Multicenter Study.”

The current standard of care to treat thromboembolism in pediatric patients who have cardiac disease is not an optimal treatment option, Portman noted. The first option is warfarin, which requires frequent monitoring and is fairly unstable in this patient population, and another option is injectable molecular heparin that can lead to parental and child fatigue. He and his team evaluated the safety and efficacy of edoxaban, a direct oral anticoagulant (DOAC) previously only used among adult patients.

Transcript

What was your goal in the ENNOBLE-ATE trial, and what are the main findings and their implications for future treatment?

We did a pediatric study testing a direct oral anticoagulant called edoxaban, which is used frequently in adults, but there is no indication in children. We wanted to test for both safety and efficacy in children age from 0 to 18 years of age. The principal finding was that it appears that it edoxaban is safe; it really was not an efficacy-driven study. But the rate of events that we were looking for, which was thromboembolism, was extremely low, both in the comparative group, which was standard of care, and the edoxaban group, suggesting that edoxaban is equivalent to standard of care.

The main issue is that for children, standard of care is not a great option, because the first option is oral warfarin, which requires frequent blood monitoring and is fairly unstable in children. There's something called an INR [international normalized ratio], in international units, and we try to have their therapeutic level within a range of 2 to 3, but it just bounces all over the place in children because their diet is changing; vitamin K, which affects warfarin absorption, is constantly changing. The other option is enoxaparin, which is an injectable molecular heparin. You have to take an injection twice daily, which is pretty nasty for little children, and it causes a lot of parental and child fatigue.

Can you discuss how edoxaban might facilitate easier treatment of cardiac diseases in children?

I would say it's easier, and I think it would lead toward a better quality of life, because edoxaban has steady state kinetics. So if you take it, we are pretty confident—from adult studies and also from the emerging pediatric studies that we did—that there's a fairly level amount of it in the blood, unlike warfarin, which is constantly changing. So they don't need the very frequent blood monitoring, which can be even 2 or 3 times a month. So that's a definite improvement in quality of life, I should say.

The other thing, with enoxaparin, obviously, they wouldn't have 2 injections daily, which also causes a lot of bruising. You don't want to see small babies and toddlers with bruises all over their body. So you can avoid that with a direct oral anticoagulant like edoxaban.

As a factor Xa inhibitor, is edoxaban’s mechanism of action identical in pediatric and adult patients?

It's exactly the same in adult patients. These mechanisms are well established. They are direct inhibitors of factor 10a. I think most of the DOACs use that mechanism. The only thing is that this has not been studied well in children. There have been some prior studies in other direct-acting anticoagulants. Edoxaban is the only one that we would give to children only once a day—so there's also a big compliance issue. Because if you take a medication, it's much easier to take a medication once a day than 2 to 3 times a day, especially with children who have to go to school, get up early, have their activities. Once a day is would be optimum.

What is the safety profile of edoxaban vs other treatments for pediatric cardiac disease?

Well, the study indicates the safety profile is virtually identical. Because of the rarity of events in this population, children who need thrombo prophylaxis who have cardiac disease, honestly, the risk of thromboembolism occurring is not huge if you're on any type of treatment. The events are rare, and bleeding events are generally rare, too. We had a standard-of-care group for a 3-month period compared to edoxaban for a 3-month period, and there were only 2 or 2 events in each group. It's pretty rare, so we really can't do a statistical analysis. We have to be satisfied with this method of doing descriptive analysis in patients who are have a rare disease with infrequent events. Although the events are infrequent, they could be devastating, and we do want to prevent those.