D'Abrantes Sofia, Male Christoph, Brown Nick, Bjursell Mikael, Ambery Philip, Berggren Anders, Mattsson Ulrika
Data Sciences and Artificial Intelligence, R&D BioPharmaceuticals, AstraZeneca, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
PLoS One. 2025 May 8;20(5):e0323137. doi: 10.1371/journal.pone.0323137. eCollection 2025.
This retrospective real-world study aimed to describe anticoagulant prescribing trends, particularly for factor Xa (FXa) inhibitors, bleeding events, and reversal agent use in pediatric patients to assess potential populations for clinical trials of the FXa inhibitor reversal agent andexanet alfa. Real-world health care data from the TriNetX Global Network and Optum's deidentified Clinformatics® Data Mart Database (CDM) were analyzed to identify patients aged <18 years old who were prescribed a direct oral FXa inhibitor, warfarin, or low-molecular-weight heparins from 2007 through 2024 (TriNetX, N = 59,780) or 2023 (CDM, N = 6470). The only anticoagulants prescribed to children were warfarin and/or low-molecular-weight heparins in 2007 and 2008 in TriNetX and from 2007 through 2010 in CDM. Prescriptions of the FXa inhibitor rivaroxaban increased from 0.4% (2009) to 18.0% (2023) in TriNetX and from 0.8% (2011) to 34.0% (2023) in CDM, with similar trends for apixaban. Relevant bleeding was reported in 9.4% of patients prescribed an FXa inhibitor in TriNetX; ≤ 0.1% of patients received andexanet alfa the day of a bleed. Among patients prescribed an FXa inhibitor, ≤ 0.1% in TriNetX and 0 in CDM received andexanet alfa the day of surgery. Direct oral FXa inhibitor use in children is growing, as is the potential for associated bleeds; however, reversal agent use is rare in this population. Given the possible unmet need and subsequent patient recruitment challenges, designing pediatric clinical trials of reversal agents requires innovative approaches.
这项回顾性真实世界研究旨在描述抗凝药物的处方趋势,尤其是针对儿科患者的Xa因子(FXa)抑制剂、出血事件及逆转剂的使用情况,以评估FXa抑制剂逆转剂andexanet alfa临床试验的潜在人群。分析了TriNetX全球网络和Optum匿名化的临床信息学数据集市数据库(CDM)中的真实世界医疗保健数据,以识别2007年至2024年(TriNetX,N = 59780)或2023年(CDM,N = 6470)年龄<18岁且开具了直接口服FXa抑制剂、华法林或低分子肝素的患者。在TriNetX中,2007年和2008年以及在CDM中2007年至2010年期间,儿童仅开具了华法林和/或低分子肝素。在TriNetX中,FXa抑制剂利伐沙班的处方比例从2009年的0.4%增至2023年的18.0%,在CDM中从2011年的0.8%增至2023年的34.0%,阿哌沙班也有类似趋势。在TriNetX中,9.4%开具FXa抑制剂的患者报告了相关出血;≤0.1%的患者在出血当天接受了andexanet alfa治疗。在开具FXa抑制剂的患者中,TriNetX中≤0.1%且CDM中为0的患者在手术当天接受了andexanet alfa治疗。儿童直接口服FXa抑制剂的使用正在增加,相关出血的可能性也在增加;然而,该人群中逆转剂的使用很少。鉴于可能存在的未满足需求以及随后的患者招募挑战,设计逆转剂的儿科临床试验需要创新方法。