Albisetti Manuela, Tartakovsky Igor, Halton Jacqueline, Bomgaars Lisa, Chalmers Elizabeth, Mitchell Lesley G, Luciani Matteo, Nurmeev Ildar, Gorbatikov Kirill, Miede Corinna, Brueckmann Martina, Brandão Leonardo R
Hematology Department University Children's Hospital Zürich Switzerland.
Boehringer Ingelheim International GmbH Ingelheim Germany.
J Am Heart Assoc. 2024 Feb 20;13(4):e028957. doi: 10.1161/JAHA.122.028957. Epub 2024 Feb 13.
Congenital heart disease (CHD) is common in children and associated with greater risk of thrombotic complications. Management of these complications with standard-of-care treatment is suboptimal for these children.
The effectiveness and safety of dabigatran were demonstrated in pivotal pediatric studies for the treatment of acute venous thromboembolism (VTE; NCT01895777) and secondary VTE prevention (NCT02197416). We report safety and efficacy outcomes from subgroup analyses of these studies for children with CHD (diagnosed according to local practice) and those without. In NCT01895777, 17/21 (81.0%) and 16/27 (59.3%) patients with CHD (including cyanotic) treated with dabigatran and standard of care, respectively, met the primary end point (complete thrombus resolution, freedom from recurrent VTE, and freedom from VTE-related death; odds ratio [OR], 0.34 [95% CI, 0.08-1.23]). In patients without CHD, 41.0% (n=64) versus 34.9% (n=22) achieved this end point with the respective treatments (OR, 0.77 [95% CI, 0.42-1.41]). Although numerical differences were observed, no heterogeneity in treatment effect of dabigatran on the composite primary end point was detected in patients with and without CHD (interaction =0.2674). In NCT02197416, recurrent VTE at 12 months occurred in 0/17 patients with CHD versus 3/194 (1.5%) without. No patient with CHD experienced major or clinically relevant nonmajor bleeding events.
Data on favorable anticoagulant alternatives for the unmet needs of children with CHD are emerging, and our exploratory results suggest that dabigatran could be an appropriate treatment choice, although challenging sample size limitations in pediatric studies require cautious interpretation of findings.
URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01895777, NCT02197416.
先天性心脏病（CHD）在儿童中很常见，且与血栓形成并发症的风险增加相关。对于这些儿童，采用标准治疗方法管理这些并发症效果欠佳。
在关键的儿科研究中证实了达比加群治疗急性静脉血栓栓塞症（VTE；NCT01895777）和继发性VTE预防（NCT02197416）的有效性和安全性。我们报告了这些研究中针对患有CHD（根据当地实践诊断）和未患CHD的儿童进行亚组分析的安全性和疗效结果。在NCT01895777中，分别接受达比加群和标准治疗的CHD（包括青紫型）患者中，达到主要终点（血栓完全溶解、无复发性VTE以及无VTE相关死亡；优势比[OR]，0.34[95%CI，0.08 - 1.23]）的患者比例分别为17/21（81.0%）和16/27（59.3%）。在未患CHD的患者中，相应治疗达到该终点的比例分别为41.0%（n = 64）和34.9%（n = 22）（OR，0.77[95%CI，0.42 - 1.41]）。尽管观察到了数值差异，但在患CHD和未患CHD的患者中，未检测到达比加群对复合主要终点的治疗效果存在异质性（交互作用 = 0.2674）。在NCT02197416中，12个月时CHD患者中无复发性VTE发生，而未患CHD的患者中有3/194（1.5%）发生。CHD患者中无患者发生大出血或临床相关非大出血事件。
针对CHD儿童未满足需求的有利抗凝替代方案的数据正在出现，我们的探索性结果表明达比加群可能是一种合适的治疗选择，尽管儿科研究中具有挑战性的样本量限制需要对研究结果进行谨慎解读。
网址：https://www.clinicaltrials.gov；唯一标识符：NCT01895777，NCT02197416。
