TY - JOUR
T1 - Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Pediatric Venous Thromboembolism Treatment and Thromboprophylaxis
T2 - A Systematic Review of the Literature
AU - Branstetter, Joshua W.
AU - Kiskaddon, Amy L.
AU - King, Madeleine A.
AU - Coalter, Carli
AU - Grubbs, Kimberly M.
AU - Fly, Hunter
AU - Male, Christoph
AU - Brandão, Leonardo
AU - Goldenberg, Neil A.
N1 - Funding Information:
L.B. reports other from Boehringer Ingelheim (BI), specifying research support and participation as a board study member; C.M. reports grants and personal fees from Bayer AG, Boehringer-Ingelheim, Bristol Myers Squibb, and Pfizer; N.A.G. reports other from Bayer, outside the submitted work; and N.A.G. receives research support and salary support from the National Institutes of Health, National Heart Lung, and Blood Institute for clinical and translational investigation in venous thromboembolism in patients younger than 21 years. N.A.G. receives consultancy fees from Daiici Sankyo Inc., Anthos Therapeutics Inc., and the Academic Research Organization CPC Clinical Research for roles in clinical trial oversight committees (e.g., steering, data and safety monitoring) in pharmaceutical industry–sponsored pediatric clinical trials of antith-rombotic agents. J.W.B., C.C., H.F., K.M.G., M.A.K., and A.L.K. do not have any conflicts of interest to disclose.
Publisher Copyright:
© 2021 Thieme Medical Publishers, Inc.. All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Venous thromboembolism (VTE) in children can lead to significant morbidity and mortality. Traditionally, treatment for thrombotic events in pediatric patients has been limited mainly to unfractionated heparin, low-molecular-weight heparin (LMWH), or vitamin K antagonists. Since the first non-vitamin K antagonist oral anticoagulant (NOAC) was approved for adult use, these agents have gained popularity for a variety of indications. This is largely due to their ease of administration, favorable pharmacokinetic and pharmacodynamic profile, decreased food interactions, and decreased need for therapeutic drug monitoring. Treating and preventing VTE with traditional anticoagulants in pediatric patients presents many challenges. This systematic review evaluated the current literature regarding pediatric NOAC trials. Additionally, based on an up-to-date query of clinicaltrials.gov, we detail current ongoing and as-yet unpublished clinical trials, study outcomes, and projected completion dates. Published pediatric NOAC trials have included 1,007 total children to date and have ranged from phase 1 to 4, with indications including both thromboembolism prophylaxis and VTE treatment. Three recent phase 3 trials, specifically involving rivaroxaban and dabigatran, have shown the agents to be at least as effective as traditional anticoagulants for acute and/or extended VTE treatment, with low frequency of recurrent thrombosis and clinically significant bleeding rates. Additionally, specially developed and tested pediatric formulations have allowed for accurate and reliable dosing, oral administration, stable pharmacokinetics and pharmacodynamics, and fewer drug or food interactions. Ongoing trials, anticipated for completion in the next few years, will reveal important information with regard to thromboembolism prophylaxis in special pediatric subpopulations and settings.
AB - Venous thromboembolism (VTE) in children can lead to significant morbidity and mortality. Traditionally, treatment for thrombotic events in pediatric patients has been limited mainly to unfractionated heparin, low-molecular-weight heparin (LMWH), or vitamin K antagonists. Since the first non-vitamin K antagonist oral anticoagulant (NOAC) was approved for adult use, these agents have gained popularity for a variety of indications. This is largely due to their ease of administration, favorable pharmacokinetic and pharmacodynamic profile, decreased food interactions, and decreased need for therapeutic drug monitoring. Treating and preventing VTE with traditional anticoagulants in pediatric patients presents many challenges. This systematic review evaluated the current literature regarding pediatric NOAC trials. Additionally, based on an up-to-date query of clinicaltrials.gov, we detail current ongoing and as-yet unpublished clinical trials, study outcomes, and projected completion dates. Published pediatric NOAC trials have included 1,007 total children to date and have ranged from phase 1 to 4, with indications including both thromboembolism prophylaxis and VTE treatment. Three recent phase 3 trials, specifically involving rivaroxaban and dabigatran, have shown the agents to be at least as effective as traditional anticoagulants for acute and/or extended VTE treatment, with low frequency of recurrent thrombosis and clinically significant bleeding rates. Additionally, specially developed and tested pediatric formulations have allowed for accurate and reliable dosing, oral administration, stable pharmacokinetics and pharmacodynamics, and fewer drug or food interactions. Ongoing trials, anticipated for completion in the next few years, will reveal important information with regard to thromboembolism prophylaxis in special pediatric subpopulations and settings.
KW - NOACs
KW - pediatric VTE
KW - thromboprophylaxis
UR - http://www.scopus.com/inward/record.url?scp=85105782612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85105782612&partnerID=8YFLogxK
U2 - 10.1055/s-0041-1725944
DO - 10.1055/s-0041-1725944
M3 - Review article
C2 - 33971679
AN - SCOPUS:85105782612
SN - 0094-6176
VL - 47
SP - 643
EP - 653
JO - Seminars in Thrombosis and Hemostasis
JF - Seminars in Thrombosis and Hemostasis
IS - 6
ER -