PMID- 37481075
OWN - NLM
STAT- MEDLINE
DCOM- 20230925
LR  - 20230928
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 21
IP  - 10
DP  - 2023 Oct
TI  - Efficacy and safety of direct oral anticoagulants in the pediatric population: a 
      systematic review and a meta-analysis.
PG  - 2784-2796
LID - S1538-7836(23)00573-1 [pii]
LID - 10.1016/j.jtha.2023.07.011 [doi]
AB  - BACKGROUND: Direct oral anticoagulants (DOACs) represent a cornerstone of adult 
      venous thromboembolism (VTE) treatment. Recently, randomized controlled trials 
      (RCTs) investigating DOACs in pediatrics have been performed. OBJECTIVES: To 
      evaluate the efficacy and safety of DOACs in the pediatric population. METHODS: 
      We systematically searched MEDLINE (PubMed), EMBASE, and ClinicalTrials.gov from 
      initiation up to August 20, 2022, for RCTs comparing DOACs to standard of care 
      (SOC) in patients aged <18 years according to PRISMA guidelines (PROSPERO 
      registration CRD42022353870). The primary analysis was performed according to the 
      anticoagulation intensity and clinical setting (ie, prophylaxis in cardiac 
      disease or treatment in VTE). Efficacy outcomes were all-cause mortality and VTE. 
      Safety outcomes were major bleeding (MB), clinically relevant non-MB, any 
      bleeding, serious adverse events, and discontinuation due to adverse events 
      (AEs). RESULTS: Seven RCTs were included in the systematic review and 6 in the 
      meta-analysis (3 prophylaxis in cardiac disease and 3 treatment in VTE). DOACs 
      showed a significant reduction of VTE recurrence for treatment (odds ratio [OR] = 
      0.42; 95% CI, 0.19-0.94) and a nonsignificant reduction in VTE occurrence in 
      prophylaxis (OR = 0.22; 95% CI, 0.03-1.55). No differences were observed for any 
      bleeding, serious AEs, and MB in prophylaxis. Nonsignificant trends were observed 
      for clinically relevant non-MB, MB in treatment, and discontinuation due to AE in 
      prophylaxis. We found a significant increase in discontinuation due to AE in 
      treatment. CONCLUSIONS: DOAC treatment seems to reduce VTE compared with SOC 
      without major safety issues in the pediatric population, whereas DOAC prophylaxis 
      seems at least comparable to SOC.
CI  - Copyright (c) 2023 International Society on Thrombosis and Haemostasis. Published 
      by Elsevier Inc. All rights reserved.
FAU - Giossi, Riccardo
AU  - Giossi R
AD  - Chemical-Clinical Analyses Unit, ASST Grande Ospedale Metropolitano Niguarda, 
      Milan, Italy; Department of Medical Biotechnology and Translational Medicine, 
      Postgraduate School of Clinical Pharmacology and Toxicology, Universita degli 
      Studi di Milano, Milan, Italy.
FAU - Menichelli, Danilo
AU  - Menichelli D
AD  - Department of General Surgery and Surgical Speciality, Sapienza University of 
      Rome, Rome, Italy.
FAU - D'Amico, Federico
AU  - D'Amico F
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
FAU - Idotta, Laura
AU  - Idotta L
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
FAU - Cirino, Mario
AU  - Cirino M
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
FAU - Scardoni, Laura
AU  - Scardoni L
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
FAU - Furlanetto, Costanza
AU  - Furlanetto C
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
FAU - Maggi, Matteo
AU  - Maggi M
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
FAU - Bernocchi, Ottavia
AU  - Bernocchi O
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
FAU - Bosca, Federica
AU  - Bosca F
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
FAU - Girlando, Luca
AU  - Girlando L
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
FAU - Pignatelli, Pasquale
AU  - Pignatelli P
AD  - Department of Clinical, Internal, Anesthesiological, and Cardiovascular Sciences, 
      Sapienza University of Rome, Rome, Italy.
FAU - Pani, Arianna
AU  - Pani A
AD  - Department of Oncology and Hemato-Oncology, Postgraduate School of Clinical 
      Pharmacology and Toxicology, Universita degli Studi di Milano, Milan, Italy.
FAU - Pastori, Daniele
AU  - Pastori D
AD  - Department of Clinical, Internal, Anesthesiological, and Cardiovascular Sciences, 
      Sapienza University of Rome, Rome, Italy. Electronic address: 
      daniele.pastori@uniroma1.it.
FAU - Tozzo, Alessandra
AU  - Tozzo A
AD  - Maternal and Infantile Department of Pediatrics, ASST Grande Ospedale 
      Metropolitano Niguarda, Milan, Italy.
FAU - Scaglione, Francesco
AU  - Scaglione F
AD  - Chemical-Clinical Analyses Unit, ASST Grande Ospedale Metropolitano Niguarda, 
      Milan, Italy; Department of Oncology and Hemato-Oncology, Postgraduate School of 
      Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, Milan, 
      Italy.
FAU - Fornasari, Diego
AU  - Fornasari D
AD  - Department of Medical Biotechnology and Translational Medicine, Postgraduate 
      School of Clinical Pharmacology and Toxicology, Universita degli Studi di Milano, 
      Milan, Italy.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20230720
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Anticoagulants)
SB  - IM
MH  - Humans
MH  - Child
MH  - Anticoagulants/therapeutic use
MH  - *Venous Thromboembolism/diagnosis/drug therapy/prevention & control
MH  - Hemorrhage/drug therapy
MH  - Blood Coagulation
MH  - *Heart Diseases/drug therapy
MH  - Administration, Oral
OTO - NOTNLM
OT  - DOACs
OT  - adverse event
OT  - apixaban
OT  - bleeding
OT  - childhood
OT  - dabigatran
OT  - edoxaban
OT  - rivaroxaban
OT  - venous thromboembolism
COIS- Declarations of competing interests R.G. received support for congress 
      participation from Mylan and acted as a consultant for Daiichi-Sankyo, outside 
      this work. M.C. received support for congress participation from Abbvie. F.S. 
      received fees as speaker or member of Advisory Boards from Bayer, MSD, Angelini, 
      and Dompe. D.F. received fees in the last 2 years as speaker or member of 
      Advisory Boards from the following companies: Alfasigma, Astellas, Bayer, 
      Grunenthal, Lundbeck, Molteni, and SPA. All other authors declare no competing 
      interests.
EDAT- 2023/07/23 01:11
MHDA- 2023/09/25 06:42
CRDT- 2023/07/22 19:24
PHST- 2023/01/31 00:00 [received]
PHST- 2023/07/04 00:00 [revised]
PHST- 2023/07/11 00:00 [accepted]
PHST- 2023/09/25 06:42 [medline]
PHST- 2023/07/23 01:11 [pubmed]
PHST- 2023/07/22 19:24 [entrez]
AID - S1538-7836(23)00573-1 [pii]
AID - 10.1016/j.jtha.2023.07.011 [doi]
PST - ppublish
SO  - J Thromb Haemost. 2023 Oct;21(10):2784-2796. doi: 10.1016/j.jtha.2023.07.011. 
      Epub 2023 Jul 20.