Chung Jong-Won, Hwang Jaechun, Kim Hyung Jun, Seo Woo-Keun, Ahn Myung-Ju, Saver Jeffrey L, Bang Oh Young
Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
Department of Neurology, School of Medicine, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea.
Int J Stroke. 2024 Jul;19(6):645-653. doi: 10.1177/17474930241239266. Epub 2024 Mar 21.
This study aimed compare efficacy of edoxaban and enoxaparin upon biomarkers of hypercoagulability in patients with cancer-related embolic stroke of undetermined source (ESUS).
In this open-label, randomized, pilot trial, patients with cancer-related ESUS within 30 days of diagnosis were randomly assigned (1:1) to receive edoxaban (60 mg once daily) or enoxaparin (1 mg/kg twice daily) for 90 days. The primary endpoint was interval change of serum D-dimer level between days 0 and 7. The secondary endpoints were microembolic signals detected by transcranial Doppler at 7 and 90 days, the modified Rankin scale score, and stroke recurrence during 90 days. Safety outcomes included major bleeding and all-cause death at 90 days.
Of 303 patients with ischemic stroke and cancer, 40 fully met enrollment criteria and were randomized. Baseline D-dimer levels were numerically higher in the edoxaban group (22.9 ± 15.9 μg/mL vs 16.9 ± 16.9 μg/mL). D-dimer level change (%) between days 0 and 7 was similar in the two groups (53.2 ± 25.7 vs 52.2 ± 52.0; = 0.11). Microembolic signals were detected in 41.1% and 43.8% at baseline, 41.2% and 42.9% at day 7, and 25.0% and 28.6% at day 90 in the edoxaban and enoxaparin groups, respectively. Non-significantly higher major bleeding (35.0% vs 10.0%, = 0.06) and 90-day mortality (40.0% vs 25.0%, = 0.31) were noted in the edoxaban group.
Edoxaban and enoxaparin were comparable with respect to the biomarkers of hypercoagulability and cerebral thromboembolism. Larger trials are warranted to compare effects of edoxaban and enoxaparin upon recurrent stroke and major bleeding in patients with cancer-related ESUS.
clinicaltrials.gov Identifier: NCT03570281 (https://clinicaltrials.gov/ct2/show/NCT03570281).
本研究旨在比较依度沙班和依诺肝素对不明来源癌症相关栓塞性卒中（ESUS）患者高凝生物标志物的疗效。
在这项开放标签、随机、试点试验中，诊断后30天内的癌症相关ESUS患者被随机分配（1:1）接受依度沙班（每日一次60mg）或依诺肝素（每日两次1mg/kg）治疗90天。主要终点是第0天和第7天之间血清D-二聚体水平的间隔变化。次要终点是经颅多普勒在第7天和第90天检测到的微栓塞信号、改良Rankin量表评分以及90天内的卒中复发。安全性结局包括90天时的大出血和全因死亡。
在303例缺血性卒中和癌症患者中，40例完全符合纳入标准并被随机分组。依度沙班组的基线D-二聚体水平在数值上更高（22.9±15.9μg/mL对16.9±16.9μg/mL）。两组第0天和第7天之间的D-二聚体水平变化（%）相似（53.2±25.7对52.2±52.0；P=0.11）。依度沙班组和依诺肝素组在基线时微栓塞信号的检出率分别为41.1%和43.8%，第7天时为41.2%和42.9%，第90天时为25.0%和28.6%。依度沙班组的大出血发生率（35.0%对10.0%，P=0.06）和90天死亡率（40.0%对25.0%，P=0.31）略高，但无统计学意义。
依度沙班和依诺肝素在高凝生物标志物和脑栓塞方面具有可比性。有必要进行更大规模的试验来比较依度沙班和依诺肝素对癌症相关ESUS患者复发性卒中和大出血的影响。
clinicaltrials.gov标识符：NCT03570281（https://clinicaltrials.gov/ct2/show/NCT035702:81）。
