Efficacy and safety of rt-PA intravenous thrombolysis for treating acute ischemic stroke beyond the therapeutic window: a Meta-analysis

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.

DOI: 10.3969/j.issn.1672-6731.2016.02.002