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Real-world experience with edoxaban for anticoagulation in children at risk for coronary artery thrombosis

Published online by Cambridge University Press:  03 November 2023

Eyal Sagiv Open the ORCID record for Eyal Sagiv [Opens in a new window] ,
David M. Newland ,
April Slee ,
Aaron K. Olson  and
Michael A. Portman
Eyal Sagiv*
Affiliation:
Division of Pediatric Cardiology, Seattle Children’s Hospital, Seattle, WA, USA
David M. Newland
Affiliation:
Department of Pharmacy, Seattle Children’s Hospital, Seattle, WA, USA
April Slee
Affiliation:
University College London, London, UK
Aaron K. Olson
Affiliation:
Division of Pediatric Cardiology, Seattle Children’s Hospital, Seattle, WA, USA Seattle Children’s Research Institute, University of Washington, Seattle, WA, USA
Michael A. Portman
Affiliation:
Division of Pediatric Cardiology, Seattle Children’s Hospital, Seattle, WA, USA Seattle Children’s Research Institute, University of Washington, Seattle, WA, USA
*
Corresponding author: E. Sagiv; Email: eyal.sagiv@seattlechildrens.org
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Abstract

Background:

Direct oral anticoagulants have the potential to improve care in children requiring chronic anticoagulation. Edoxaban has favourable pharmacokinetics that could benefit younger patients but data on long-term safety and efficacy for specific paediatric indications are lacking.

Study Aims:

We present a single-centre experience using edoxaban in children who require chronic anticoagulation for large coronary artery aneurysms secondary to Kawasaki disease.

Methods:

Weight-based dosing of once-daily oral edoxaban was offered as alternative to standard anticoagulation for patients aged 1–18 years. Chart review was performed for a median follow-up period of 49 months on edoxaban. Steady-state pharmacokinetics and pharmacodynamics of edoxaban were also explored.

Results:

Sixteen patients on chronic therapy with edoxaban were included. No major bleeding events were reported. Two patients experienced coronary artery thrombosis after 23 and 38 months on edoxaban, 7 and 11 years after diagnosed with Kawasaki disease, respectively. This predicts 70% event-free rate at 12 years from diagnosis. Area under the curve estimates over the dosing interval of 24 hours were similar to those reported in adults.

Conclusions:

Edoxaban use is feasible and well-tolerated for long-term use in paediatric population. We suggest appropriate exposure using weight-based once-daily dosing strategy that may be comparable to standard-of-care anticoagulation in prevention of coronary artery thrombosis. Larger studies are needed to evaluate long-term safety and efficacy of edoxaban in this population.

Keywords

Coronary artery aneurysmsedoxabandirect oral anticoagulantsKawasakivasculitis
Type
Original Article
Information
Cardiology in the Young , Volume 34 , Issue 4 , April 2024 , pp. 870 - 875
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Copyright
© The Author(s), 2023. Published by Cambridge University Press

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References

Newburger, JW, Takahashi, M, Burns, JC. Kawasaki disease. J Am Coll Cardiol 2016; 67: 1738–1749.10.1016/j.jacc.2015.12.073CrossRefGoogle ScholarPubMed
McCrindle, BW, Rowley, AH, Newburger, JW, et al. Diagnosis, treatment, and long-term management of kawasaki disease: a scientific statement for health professionals from the American heart association. Circulation 2017; 135: e927–e999.10.1161/CIR.0000000000000484CrossRefGoogle ScholarPubMed
McCrindle, BW, Manlhiot, C, Newburger, JW, et al. Medium-term complications associated with coronary artery aneurysms after kawasaki disease: a study from the international kawasaki disease registry. J Am Heart Assoc 2020; 9: e016440.10.1161/JAHA.119.016440CrossRefGoogle ScholarPubMed
Monagle, P, Newall, F. Management of thrombosis in children and neonates: practical use of anticoagulants in children. Hematology Am Soc Hematol Educ Program 2018; 2018: 399–404.10.1182/asheducation-2018.1.399CrossRefGoogle ScholarPubMed
Cohen, O, Levy-Mendelovich, S, Ageno, W. Rivaroxaban for the treatment of venous thromboembolism in pediatric patients. Expert Rev Cardiovasc Ther 2020; 18: 733–741.10.1080/14779072.2020.1823218CrossRefGoogle ScholarPubMed
Jones, S, Monagle, P, Manias, E, et al. Quality of life assessment in children commencing home INR self-testing. Thromb Res 2013; 132: 37–43.10.1016/j.thromres.2013.05.011CrossRefGoogle ScholarPubMed
Baker, AL, Vanderpluym, C, Gauvreau, KA, et al. Safety and efficacy of warfarin therapy in kawasaki disease. J Pediatr 2017; 189: 61–65.10.1016/j.jpeds.2017.04.051CrossRefGoogle ScholarPubMed
Albisetti, M. Use of direct oral anticoagulants in children and adolescents. Hamostaseologie 2020; 40: 64–73.Google ScholarPubMed
Young, G, Lensing, AWA, Monagle, P, et al. Rivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr phase 3 dose-exposure-response evaluation. J Thromb Haemost 2020; 18: 1672–1685.10.1111/jth.14813CrossRefGoogle ScholarPubMed
Male, C, Lensing, AWA, Palumbo, JS, et al. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol 2020; 7: e18–e27.10.1016/S2352-3026(19)30219-4CrossRefGoogle ScholarPubMed
McCrindle, BW, Michelson, AD, Van Bergen, AH, et al. Thromboprophylaxis for children post-fontan procedure: insights from the UNIVERSE study. J Am Heart Assoc 2021; 10: e021765.10.1161/JAHA.120.021765CrossRefGoogle ScholarPubMed
Bhatt, MD, Portman, MA, Berger, F, et al. ENNOBLE-ATE trial: an open-label, randomised, multi-centre, observational study of edoxaban for children with cardiac diseases at risk of thromboembolism. Cardiol Young 2021; 31: 1213–1219.10.1017/S1047951121002523CrossRefGoogle ScholarPubMed
Portman, MA, Jacobs, JP, Newburger, JW, et al. Edoxaban for thromboembolism prevention in pediatric patients with cardiac disease. J Am Coll Cardiol 2022; 80: 2301–2310.10.1016/j.jacc.2022.09.031CrossRefGoogle ScholarPubMed
He, L, Gajee, R, Mangaraj, R, et al. Validation and clinical application of dried blood spot assay for quantitative assessment of edoxaban in healthy adults. Bioanalysis 2020; 12: 393–407.10.4155/bio-2019-0180CrossRefGoogle ScholarPubMed
Gosselin, RC, Adcock, DM, Bates, SM, et al. International council for standardization in haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost 2018; 118: 437–450.Google ScholarPubMed
Ono, R, Nishimura, K, Takahashi, H, et al. Impact of renal function on anti-factor xa activity concentrations with edoxaban use in patients with non-valvular atrial fibrillation. Drugs R D 2022; 22: 281–288.10.1007/s40268-022-00403-5CrossRefGoogle ScholarPubMed
National Kidney Founudation. Pediatric GFR Calculator. www.kidney.org/professionals/kdoqi/gfr_calculatorPed (Accesseds 8/7/2023).Google Scholar
Kaplan, EL, Meier, P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.10.1080/01621459.1958.10501452CrossRefGoogle Scholar
Parasrampuria, DA, Truitt, KE. Pharmacokinetics and pharmacodynamics of edoxaban, a non-vitamin K antagonist oral anticoagulant that inhibits clotting factor Xa. Clin Pharmacokinet 2016; 55: 641–655.10.1007/s40262-015-0342-7CrossRefGoogle ScholarPubMed
von Vajna, E, Alam, R, So, T-Y. Current clinical trials on the use of direct oral anticoagulants in the pediatric population. Cardiol Ther 2016; 5: 19–41.10.1007/s40119-015-0054-yCrossRefGoogle ScholarPubMed
VanderPluym, C, Esteso, P, Ankola, A, et al. Real-world use of apixaban for the treatment and prevention of thrombosis in children with cardiac disease. J Thromb Haemost 2023; 21: 1601–1609.10.1016/j.jtha.2023.03.005CrossRefGoogle ScholarPubMed
Iemura, M, Ishii, M, Sugimura, T, et al. Long term consequences of regressed coronary aneurysms after kawasaki disease: vascular wall morphology and function. Heart 2000; 83: 307–311.10.1136/heart.83.3.307CrossRefGoogle ScholarPubMed
Orenstein, JM, Shulman, ST, Fox, LM, et al. Three linked vasculopathic processes characterize kawasaki disease: a light and transmission electron microscopic study. PLoS One 2012; 7: e38998.10.1371/journal.pone.0038998CrossRefGoogle ScholarPubMed
Dionne, A, Ibrahim, R, Gebhard, C, et al. Difference between persistent aneurysm, regressed aneurysm, and coronary dilation in kawasaki disease: an optical coherence tomography study. Can J Cardiol 2018; 34: 1120–1128.10.1016/j.cjca.2018.05.021CrossRefGoogle ScholarPubMed
Newburger, JW, Takahashi, M, Gerber, MA, et al. Diagnosis, treatment, and long-term management of kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis, and kawasaki disease, council on cardiovascular disease in the young, american heart association. Pediatrics 2004; 114: 1708–1733.10.1542/peds.2004-2182CrossRefGoogle Scholar
Patel, AS, Bruce, M, Harrington, W, et al. Coronary artery stenosis risk and time course in kawasaki disease patients: experience at a US tertiary pediatric centre. Open Heart 2015; 2: e000206.10.1136/openhrt-2014-000206CrossRefGoogle Scholar
Monagle, P, Lensing, AWA, Thelen, K, et al. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies. Lancet Haematol 2019; 6: e500–e509.10.1016/S2352-3026(19)30161-9CrossRefGoogle ScholarPubMed
Payne, RM, Burns, KM, Glatz, AC, et al. A multi-national trial of a direct oral anticoagulant in children with cardiac disease: design and rationale of the safety of ApiXaban on pediatric heart disease on the preventioN of embolism (SAXOPHONE) study. Am Heart J 2019; 217: 52–63.10.1016/j.ahj.2019.08.002CrossRefGoogle ScholarPubMed
Kobayashi, RL, Cetatoiu, MA, Esteso, P, et al. Apixaban anticoagulation in children and young adults supported with the HeartMate 3 Ventricular assist device. ASAIO J 2023; 69: e267–e269.10.1097/MAT.0000000000001889CrossRefGoogle Scholar
Röshammar, D, Huang, F, Albisetti, M, et al. Pharmacokinetic modeling and simulation support for age- and weight-adjusted dosing of dabigatran etexilate in children with venous thromboembolism. J Thromb Haemost 2021; 19: 1259–1270.10.1111/jth.15277CrossRefGoogle ScholarPubMed
Lin, S-Y, Kuo, C-H, Ho, L-T, et al. Factors associated with edoxaban concentration among patients with atrial fibrillation. Front Pharmacol 2021; 12: 736826.10.3389/fphar.2021.736826CrossRefGoogle ScholarPubMed