Abstract: Objective  To analyze the efficacy and safety of reteplase versus alteplase in acute ischemic stroke (AIS) patients complicated with arrhythmia.
Methods  The RAISE (reteplase versus alteplase for acute ischaemic stroke within 4.5 hours) study was a multicenter, randomized, controlled, open-label, outcome-blinded phase Ⅲ clinical trial designed to compare reteplase and alteplase in the treatment of AIS patients within 4.5 hours of onset. This study was a post-hoc analysis of AIS patients complicated with arrhythmia enrolled in the RAISE study. Patients were divided into the reteplase group and the alteplase group according to the thrombolytic agent administered. The primary efficacy outcome was the proportion of patients achieving an mRS score of 0-1 at 90 days post-thrombolysis, and the primary safety outcome was the occurrence of symptomatic intracranial hemorrhage within 36 hours post-thrombolysis. This study compared the clinical efficacy and safety differences between the two thrombolytic agents in AIS patients complicated with arrhythmia. 
Results  A total of 129 AIS patients complicated with arrhythmia were included in this study, with 59 cases in the reteplase group and 70 cases in the alteplase group. For the primary efficacy outcome, the proportion of patients achieving an mRS score of 0-1 at 90 days post-thrombolysis in the reteplase group showed a trend toward being higher than that in the alteplase group, but the difference was not statistically significant (68.4% vs. 66.2%, RR 1.07, 95%CI 0.85-1.35, P=0.560). For the secondary efficacy outcome, the proportion of patients with significant neurological improvement (defined as a reduction in NIHSS score≥4 points or an NIHSS score≤1) at 7 days post-thrombolysis was significantly higher in the reteplase group than in the alteplase group (78.9% vs. 61.2%, RR 1.25, 95%CI 1.03-1.51, P=0.021). No statistically significant differences were observed in all safety outcomes between the two thrombolytic agents in the treatment of AIS patients complicated with arrhythmia. Specifically, the rates of symptomatic intracranial hemorrhage within 36 hours post-thrombolysis were 1.7% in the reteplase group and 1.4% in the alteplase group (RR 1.07, 95%CI 0.07-15.25, P=0.963), and the mortality within 90 days post-thrombolysis was 10.2% and 5.7%, respectively (RR 1.41, 95%CI 0.49-4.07, P=0.520).
Conclusions  For AIS patients complicated with arrhythmia within 4.5 hours of onset, reteplase and alteplase exhibited comparable efficacy and safety. Therefore, reteplase may be considered as an alternative to alteplase in thrombolytic therapy.

Key words: Acute ischemic stroke; Reteplase; Alteplase; Arrhythmia

摘要： 目的 分析瑞替普酶与阿替普酶治疗急性缺血性卒中（acute ischemic stroke, AIS）合并心律失常患者的有效性及安全性。 
方法 瑞替普酶与阿替普酶治疗发病4.5 h内AIS（reteplase versus alteplase for acute ischaemic stroke within 4.5 hours，RAISE）研究是1项多中心、随机、对照、开放标签、终点盲法的Ⅲ期临床试验，旨在比较瑞替普酶与阿替普酶对发病4.5 h内AIS患者的治疗效果。本研究是针对RAISE研究中AIS合并心律失常患者的事后分析，根据溶栓药物使用情况将患者分为瑞替普酶组和阿替普酶组，以溶栓后90 d mRS评分0～1分为主要有效性指标、溶栓后36 h内症状性颅内出血为主要安全性指标，比较两种溶栓药物对AIS合并心律失常患者的临床有效性和安全性差异。
结果 本研究共纳入129例AIS合并心律失常患者，其中瑞替普酶组59例，阿替普酶组70例。对于主要有效性指标，瑞替普酶组溶栓后90 d mRS评分0～1分的比例有高于阿替普酶组的趋势，但差异无统计学意义（68.4% vs. 66.2%，RR 1.07，95%CI 0.85～1.35，P=0.560）。对于次要有效性指标，瑞替普酶组溶栓后7 d神经功能显著改善（NIHSS评分降低≥4分或NIHSS评分≤1分）的比例较阿替普酶组更高（78.9% vs. 61.2%，RR 1.25，95%CI 1.03～1.51，P=0.021）。两种药物治疗AIS合并心律失常患者在各项安全性指标方面均未观察到具有统计学意义的差异。其中，瑞替普酶组与阿替普酶组溶栓后36 h内症状性颅内出血的比例分别为1.7%和1.4%（RR 1.07，95%CI 0.07～15.25，P=0.963），溶栓后90 d内死亡率分别为10.2%和5.7%（RR 1.41，95%CI 0.49～4.07，P=0.520）。
结论 对于发病4.5 h内的AIS合并心律失常患者，瑞替普酶与阿替普酶的有效性和安全性相似，溶栓治疗中瑞替普酶可考虑作为阿替普酶的替代方案。

关键词: 急性缺血性卒中; 瑞替普酶; 阿替普酶; 心律失常