重组型组织纤溶酶原激活剂联合他汀扩大时间窗溶栓治疗急性脑梗死研究

A pilot safety and efficacy study of dual treatment with recombinant tissue plasminogen activator and atorvastain in acute ischemic stroke in the 4.5-6 hour window

目的：探讨阿托伐他汀联合重组型组织纤溶酶原激活剂（rt-PA）治疗发病4.5～6 h急性脑梗死的安全性和有效性。方法发病4.5～6 h内急性脑梗死患者42例，随机分为对照组和试验组。试验组入院后即予阿托伐他汀联合rt-PA治疗（剂量为0.6 mg/kg，最大剂量不超过90 mg）；溶栓治疗后24 h如无出血等并发症发生，可予阿司匹林和阿托伐他汀治疗；对照组入院后常规予阿司匹林和阿托伐他汀治疗；同时予控制血压和血糖、对症治疗等药物治疗。随访两组90 d主要终点指标是症状性脑出血发生率；次要终点指标是治疗后24 h神经功能改善情况和发病3个月临床预后[改良Rankin量表（mRS）评分]。结果症状性脑出血2例，试验组1例，对照组1例，均出现在大面积脑梗死患者，无一例死亡病例。试验组早期神经功能改善较对照组高（47.6%vs.33.3%），差异有统计学意义（P＜0.05）；试验组临床预后良好（mRS＜2）者较对照组增加（47.6% vs.38.1%），有好转趋势，但差异无统计学意义（P＞0.05）。结论发病4.5～6 h内他汀联合rt-PA治疗是安全的，并可改善急性脑梗死早期神经功能。

Objective To evaluate the safety and efficacy of combining statin with recombinant tissue plasminogen activator （rtPA） administration in acute ischemic stroke in the 4.5-6 hours window. Methods In this open-label, pilot study, patients with acute ischaemic stroke were randomly assigned to the test group or the control group within 4.5-6 h after the onset of symptoms. The test group received atorvastain（80 mg/kg） with rtPA （0.6 mg/kg）, the control group received aspirin（100-300 mg/d） and atorvastain（20 mg/kg）.The primary endpoint was rates of symptomatic intracranial haemorrhage. Secondary endpoints is neurological improvement at 24-48 h after symptom onset and favorable outcome at day 90.Results Forty-two patients were enrolled, symptomatic intracerebral hemorrhage occurred in 2 patients. Of these, 1（4.6%） was in the test group, 1（4.6%） was in the control group. no differences in symptomatic intracerebral hemorrhage rates were found between the two groups, no patients died in the 90 days. The rates of early neurological improvement at 24 h after symptom onset was more frequent in the test group（47.6%） compared with the control group（33.3%,P〈0.05）. The favorable outcome rates at day 90 were similar in the test group（47.6%） compared with the control group（38.1%P〉0.05）, However, the number of patients who benefited from the test group was slightly higher than the control group （47.6%vs. 38.1%）.Conclusion The combination of atorvastain and intravenous rtPA is potentially safe in patients with acute ischemic stroke in the 4.5-6 hours window and may improve early neurological function.Continued evaluation of this treatment combination is warranted.