重组组织型纤溶酶原激活物治疗合并大脑中动脉高密度征的急性缺血性卒中有效性和安全性的系统评价

Efficacy and safety of rt-PA intravenous thrombolysis in the treatment of acute ischemic stroke with hyperdense middle cerebral artery sign: a systematic review

目的系统评价合并大脑中动脉高密度征（HMCAS）的急性缺血性卒中患者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。方法以hyperdense middle cerebral arterysign/HMCAS/hyperdense artery sign/hyperdense cerebral artery sign、ischemic stroke/cerebral infarction/brain infraction/cerebral embolism、thrombolysis/thrombolytic therapy/rt-PA/recombinant tissue plasminogenactivator,以及大脑中动脉高密度征/致密动脉征/大脑中动脉致密征/脑动脉高密度征、缺血性脑卒中/缺血性卒中/脑梗死/脑梗塞/脑栓塞、溶栓治疗/rt-PA/重组组织型纤溶酶原激活剂等中英文词组为检索词,计算机检索1994年1月-2014年12月美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、Cochrane临床对照试验中心注册库,以及中国生物医学文献数据库等收录的关于rt-PA静脉溶栓治疗合并HMCAS的急性缺血性卒中随机或非随机对照临床试验;分别采用Newcastle-Ottawa量表和Rev Man5.2统计软件行文献质量评价和Meta分析。结果经剔除重复和不符合纳入标准者,166篇英文文献中最终纳入8项非随机对照临床试验共11 373例患者[2455例合并HMCAS（rt-PA静脉溶栓治疗2316例、安慰剂治疗139例）、8918例未合并HMCAS]。Meta分析显示：rt-PA静脉溶栓组患者不良预后风险低于安慰剂组（OR=0.360,95%CI：0.150-0.850;P=0.020）,但症状性颅内出血发生率组间差异无统计学意义（OR=1.640,95%CI：0.380-7.040;P=0.500）;合并HMCAS患者rt-PA静脉溶栓治疗不良预后风险高于未合并者（OR=2.830,95%CI：2.550-3.150;P=0.000）,但症状性颅内出血发生率组间差异无统计学意义（OR=1.090,95%CI：0.500-2.410;P=0.820）。结论尽管rt-PA静脉溶栓治疗合并HMCAS的急性缺血性卒中患者安全、有效,但发病3个月时易出现不良预后,而发生症状性颅内出血风险较低。

ObjectiveTo systematically review the efficacy and safety of recombinant tissue- typeplasminogen activator（rt- PA） intravenous thrombolysis in the treatment of acute ischemic stroke withhyperdense middle cerebral artery sign（HMCAS） on CT images.MethodsSearch online databases suchas Pub Med, EMBASE/SCOPUS, Cochrane Central Register of Controlled Trials（CENTRAL） and ChinaBiology Medicine（CBM） from January 1994 to December 2014 with key words： hyperdense middle cerebralartery sign/HMCAS/hyperdense artery sign/hyperdense cerebral artery sign, ischemic stroke/cerebralinfarction/brain infarction/cerebral embolism, thrombolysis/thrombolytic therapy/rt- PA/recombinant tissueplasminogen activator both in Chinese and English, to collect randomized controlled trials（RCTs） or non-RCTs about rt- PA treating patients with acute ischemic stroke and HMCAS. Two reviewers independentlyscreened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the riskof bias of included studies. Newcastle- Ottawa Scale（NOS） was used for quality assessment, and Meta-analysis was performed using Rev Man 5.2 software.ResultsA total of 8 studies were included afterexcluding duplicate ones and those which did not meet the inclusion criteria from 166 articles. There were11 373 patients, including 2455 cases complicated with HMCAS（2316 treated by rt-PA and 139 treated byplacebo） and 8918 cases without HMCAS. Meta-analysis showed the occurrence of unfavorable outcome inrt-PA treatment was significantly decreased compared to placebo in HMCAS-positive patients（OR = 0.360,95%CI： 0.150-0.850; P = 0.020）, while there was no statistical difference in the occurrence of symptomaticintracerebral hemorrhage（s ICH） between rt- PA and placebo treatment in HMCAS- positive patients（OR =1.640, 95%CI： 0.380-7.040; P = 0.500）. Meta-analysis also showed unfavorable outcome of rt-PA treatmentwas significantly higher in HMCAS- positive than in HMCAS- negative patients（OR = 2.830, 95% CI：2.550-3.150; P = 0.000）, while there was no statistical difference in the occurrence of s ICH after rt- PAtreatment（OR = 1.090, 95% CI： 0.500-2.410; P = 0.820）.ConclusionsAlthough rt- PA intravenousthrombolysis is safe and effective in the treatment for HMCAS-positive patients with acute ischemic stroke,unfavorable outcome is easy to occur after 3 months of onset, however, the risk of symptomatic intracerebralhemorrhage is low.