近日，北京天坛医院王拥军教授团队比较了瑞替普酶与阿替普酶治疗急性缺血性卒中的疗效与安全性。该项研究成果发表在2024年6月14日出版的《新英格兰医学杂志》上。

阿替普酶是早期再灌注治疗中使用的标准药物，但需要替代性溶栓药物。与阿替普酶相比，瑞替普酶在急性缺血性脑卒中患者中的疗效和安全性尚不清楚。

研究组以1:1的比例将缺血性卒中症状出现后4.5小时内的患者随机分为静脉注射瑞替普酶（一次18 mg的推注，30分钟后第二次18 mg）或静脉注射阿替普酶（0.9 mg/公斤体重；最大剂量90 mg）。主要疗效结局是良好的功能预后，定义为90天时改良Rankin量表评分为0或1（范围为0[无神经功能缺损、无症状或完全康复]至6[死亡]）。主要安全性结局是症状出现后36小时内出现症状性颅内出血。

共有707名患者被分配接受瑞替普酶治疗，705名患者分配接受阿替普酶治疗。瑞替普酶组79.5%的患者和阿替普酶组70.4%的患者出现了良好的功能预后（风险比为1.13；95%置信区间[CI]为1.05至1.21；非劣效性P<0.001，优效性P=0.002）。瑞替普酶组700名患者中有17名（2.4%）和阿替普酶组699名患者中有14名（2.0%）在发病后36小时内出现症状性颅内出血（风险比为1.21；95%可信区间为0.54至2.75）。90天时，瑞替普酶组颅内出血的发生率高于阿替普酶组（7.7%vs.4.9%；风险比1.59；95%置信区间1.00-2.51），不良事件的发生率也高于阿替普酶组（91.6%vs.82.4%；风险比1.11；95%可信区间1.03-1.20）。

研究结果表明，在症状出现后4.5小时内的缺血性卒中患者中，瑞替普酶比阿替普酶更有可能产生良好的功能预后。

附：英文原文

Title: Reteplase versus Alteplase for Acute Ischemic Stroke

Author: Shuya Li, Hong-Qiu Gu, Hao Li, Xuechun Wang, Aoming Jin, Shuming Guo, Guozhi Lu, Fengyuan Che, Weiwei Wang, Yan Wei, Yilong Wang, Zixiao Li, Xia Meng, Xingquan Zhao, Liping Liu, Yongjun Wang

Issue&Volume: 2024-06-14

Abstract:

BACKGROUND

Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear.

METHODS

We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset.

RESULTS

A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P=0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20).

CONCLUSIONS

Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase.

DOI: NJ202406140000010

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2400314