Abstract:

Objective  To evaluate the efficacy and safety of thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute ischemic stroke with broadened therapeutic window (4.50-6.00 h).  Methods  Online databases, such as PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang data were searched from January 1980 to August 2015 with key words: acute ischemic stroke, thrombolytic therapy, beyond 4.5 hours. The included studies were evaluated according to Jadad Scale, and Meta-analysis was performed by using RevMan 5.3 software.  Results  There were 681 relevant records through preliminary searching, and 3 randomized controlled trials (RCTs) were finally included, involving 2033 patients with acute ischemic stroke (1029 patients in rt-PA thrombolytic therapy and 1004 patients in placebo therapy), who were treated within 6 h from the onset of symptoms. Results of Meta-analysis showed there were no statistical differences between rt-PA group and placebo group on modified Rankin Scale (mRS) score (RR = 1.070, 95%CI: 0.940-1.220; P = 0.310), Barthel Index (BI) score (RR = 1.040, 95%CI: 0.940-1.160; P = 0.430) and mortality (RR = 1.260, 95%CI: 0.990-1.610; P = 0.060). However, the incidence of intracerebral hemorrhage (ICH) in rt-PA group was significantly higher than that in placebo group (RR = 1.550, 95% CI: 1.030-2.340; P = 0.030).  Conclusions Thrombolytic therapy with rt-PA in broadened therapeutic window (4.50-6.00 h) is not effective for treating acute ischemic stroke, and the risk of ICH is increased with rt-PA treatment. However, this conclusion still needs to be verified with more high-quality, multi-center, large-sample RCTs.

Key words:

摘要：

目的 系统评价超时间窗（4.50 ~ 6.00 h）的急性缺血性卒中患者行重组组织型纤溶酶原激活物（rt-PA）静脉溶栓治疗的有效性和安全性。方法 分别以缺血性卒中/脑梗死/脑梗塞、溶栓治疗、延长时间窗，以及acute ischemic stroke、thrombolytic therapy、beyond 4.5 hours等中英文词组为检索词，计算机检索1980 年1 月-2015 年8 月美国国立医学图书馆生物医学信息检索系统、Cochrane 图书馆、中国知网中国知识基础设施工程、万方数据库等收录的rt-PA 静脉溶栓治疗超时间窗（4.50 ~ 6.00 h）急性缺血性卒中随机对照临床试验；Jadad 量表和RevMan 5.3 统计软件进行文献质量评价和Meta 分析。结果 共获得681 篇文献，经剔除重复和不符合纳入标准者，最终纳入3 项随机对照临床试验计2033 例急性缺血性卒中（发病< 6 h）患者（rt-PA 静脉溶栓组1029 例、安慰剂组1004 例）。Meta 分析显示：rt-PA 静脉溶栓与安慰剂对改善患者神经功能（RR = 1.070，95%CI：0.940 ~ 1.220；P = 0.310）和日常生活活动能力（RR = 1.040，95%CI：0.940 ~ 1.160；P = 0.430）、降低病死率（RR = 1.260，95%CI：0.990 ~ 1.610；P = 0.060）差异无统计学意义，但rt-PA 静脉溶栓组患者脑出血发生率高于安慰剂组（RR = 1.550，95%CI：1.030 ~ 2.340；P = 0.030）。结论 rt-PA 静脉溶栓治疗超时间窗（4.50 ~ 6.00 h）急性缺血性卒中无明显疗效且可能增加脑出血风险，高质量证据尚待大样本多中心随机对照临床试验加以验证。

关键词: 脑缺血, 组织型纤溶酶原激活物, Meta分析