Translational Stroke Research

, Volume 7, Issue 2, pp 111–119 | Cite as

Thrombolysis with Low-Dose Tissue Plasminogen Activator 3–4.5 h After Acute Ischemic Stroke in Five Hospital Groups in Japan

  • Ryuta Morihara
  • Syoichiro Kono
  • Kota Sato
  • Nozomi Hishikawa
  • Yasuyuki Ohta
  • Toru Yamashita
  • Kentaro Deguchi
  • Yasuhiro Manabe
  • Yoshiki Takao
  • Kenichi Kashihara
  • Satoshi Inoue
  • Hideki Kiriyama
  • Koji Abe
Original Article


Clinical data from Japan on the safety and real-world outcomes of alteplase (tPA) thrombolysis in the extended therapeutic window are lacking. The aim of this study was to assess the safety and real-world outcomes of tPA administered within 3–4.5 h of stroke onset. The study comprised consecutive acute ischemic stroke patients (n = 177) admitted across five hospitals between September 2012 and August 2014. Patients received intravenous tPA within <3 or 3–4.5 h of stroke onset. Endovascular therapy was used for tPA-refractory patients. In the 3–4.5 h subgroup (31.6 % of patients), tPA was started 85 min later than the <3 h group (220 vs. 135 min, respectively). However, outcome measures were not significantly different between the <3 and 3–4.5 h subgroups for recanalization rate (67.8 vs. 57.1 %), symptomatic intracerebral hemorrhage (2.5 vs. 3.6 %), modified Rankin Scale score of 0–1 at 3 months (36.0 vs. 23.4 %), and mortality (6.9 vs. 8.3 %). We present data from 2005 to 2012 using a therapeutic window <3 h showing comparable results. tPA following endovascular therapy with recanalization might be superior to tPA only with recanalization (81.0 vs. 59.1 %). Compared with administration within 3 h of ischemic stroke onset, tPA administration within 3–4.5 h of ischemic stroke onset in real-world stroke emergency settings at multiple sites in Japan is as safe and has the same outcomes.


Acute stroke Edaravone Endovascular treatment Intracerebral hemorrhage Recanalization Tissue-type plasminogen activator 



Diffusion-weighted imaging


Diffusion-weighted imaging—Alberta Stroke Program Early Computed Tomography Score


Intracerebral hemorrhage


National Institutes of Health Stroke Scale


Magnetic resonance angiography


Magnetic resonance imaging


modified Rankin Scale


Tissue plasminogen activator


Compliance with Ethical Standards

The study was approved by the ethics committee of Okayama University (#1505-025).


This work was supported in part by Grants-in-Aid for Scientific Research (B) 2529320216 and (C) 24591263 and Grant-in-Aid for Challenging Research 24659651 from the Ministry of Education, Culture, Sports, Science and Technology, and by Grants-in-Aid from the Research Committees (H. Mizusawa, I. Nakano, M. Nishizawa, H. Sasaki, and M. Aoki) from the Ministry of Health, Labor and Welfare of Japan.

Conflict of Interest

Edaravone has been marketed in Japan since 2001 by Mitsubishi Tanabe Pharma (Osaka, Japan). K. Abe received honoraria from Mitsubishi Tanabe Pharma (Osaka, Japan) in 2012, 2013, and 2014. All remaining authors report no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ryuta Morihara
    • 1
  • Syoichiro Kono
    • 1
  • Kota Sato
    • 1
  • Nozomi Hishikawa
    • 1
  • Yasuyuki Ohta
    • 1
  • Toru Yamashita
    • 1
  • Kentaro Deguchi
    • 1
  • Yasuhiro Manabe
    • 2
  • Yoshiki Takao
    • 3
  • Kenichi Kashihara
    • 4
  • Satoshi Inoue
    • 5
  • Hideki Kiriyama
    • 5
  • Koji Abe
    • 1
  1. 1.Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama UniversityOkayamaJapan
  2. 2.Okayama National Hospital Medical CenterOkayamaJapan
  3. 3.Kurashiki Heisei HospitalKurashikiJapan
  4. 4.Okayama Kyokuto HospitalOkayamaJapan
  5. 5.Department of NeurosurgeryOkayama Citizens’ HospitalOkayamaJapan

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