Cui Yu, Chen Hui-Sheng
Department of Neurology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenhe District, Shenyang, 110016, China.
Ann Clin Transl Neurol. 2025 Feb;12(2):355-365. doi: 10.1002/acn3.52280. Epub 2024 Dec 15.
ARAIS trial failed to demonstrate benefit of argatroban as an adjunct to alteplase for stroke. Given differences between anterior circulation stroke (ACS) and posterior circulation stroke (PCS), we performed prespecified secondary analysis to investigate whether benefit of argatroban was different between ACS and PCS.
In secondary analysis of ARAIS, patients with definite stroke territories based on responsible vessel examination were classified into ACS and PCS. The primary outcome was a 90-day excellent functional outcome (modified Rankin Scale score of 0 to 1). The efficacy was compared between argatroban plus alteplase and alteplase alone.
This study included 356 patients from the full analysis set of ARAIS trial: 283 in the ACS group and 73 in the PCS group. Compared with alteplase alone, a higher likelihood of 90-day excellent functional outcome was associated with argatroban plus alteplase in PCS group (78.1% versus 61.0%; adjusted RD, 14.4%; 95% CI, 1.6% to 27.2%; p = 0.03), but similar in ACS group (61.7% versus 62.7%; adjusted RD, -2.4%; 95% CI, -10.1% to 5.2%; p = 0.54). After controlling unbalanced sample size bias by propensity score matching, significant interaction between efficacy and stroke territories was found (p = 0.01). The risk of symptomatic intracranial hemorrhage was higher following argatroban plus alteplase than alteplase alone in ACS group (p = 0.02).
Argatroban plus alteplase, compared with alteplase alone, was associated with improved functional outcomes in PCS. This study first demonstrated better benefits of argatroban plus alteplase in PCS, which deserves to be confirmed.
急性缺血性卒中阿加曲班辅助溶栓研究（ARAIS试验）未能证明阿加曲班辅助阿替普酶治疗卒中的益处。鉴于前循环卒中（ACS）和后循环卒中（PCS）之间存在差异，我们进行了预先设定的二次分析，以研究阿加曲班在ACS和PCS中的益处是否不同。
在ARAIS试验的二次分析中，根据责任血管检查确定卒中区域的患者被分为ACS组和PCS组。主要结局为90天时功能预后良好（改良Rankin量表评分为0至1分）。比较阿加曲班联合阿替普酶与单用阿替普酶的疗效。
本研究纳入了ARAIS试验全分析集的356例患者：ACS组283例，PCS组73例。与单用阿替普酶相比，PCS组中阿加曲班联合阿替普酶90天时功能预后良好的可能性更高（78.1%对61.0%；调整后差值，14.4%；95%可信区间，1.6%至27.2%；p = 0.03），但在ACS组中相似（61.7%对62.7%；调整后差值，-2.4%；95%可信区间，-10.1%至5.2%；p = 0.54）。通过倾向评分匹配控制样本量不平衡偏差后，发现疗效与卒中区域之间存在显著交互作用（p = 0.01）。ACS组中，阿加曲班联合阿替普酶治疗后有症状性颅内出血的风险高于单用阿替普酶（p = 0.02）。
与单用阿替普酶相比，阿加曲班联合阿替普酶与PCS患者功能预后改善相关。本研究首次证明了阿加曲班联合阿替普酶在PCS中有更好的疗效，值得进一步证实。
