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Reperfusion after 4·5 hours reduces infarct growth and improves clinical outcomes


  • Subjects codes: [44] Acute Cerebral Infarction, [58] Computerized tomography and Magnetic Resonance Imaging, [73] Thrombolysis.
  • Conflict of interest:
  • M. R. P., S. C., B. C. V. C., and L. C. have no disclosures.
  • C. R. L., M. W. P., and C. F. B. have accepted honoraria or consultancy and travel grants from Boehinger-Ingelheim and Sanofi-Aventis.
  • G. A. D. is a member of Boehinger-Ingelheim, PAION, Servier, and Sanofi-Aventis advisory boards.
  • S. M. D. is a member of Servier, Novo Nordisk, and Sanofi-Aventis advisory boards.



The currently proven time window for thrombolysis in ischemic stroke is 4·5 h. Beyond this, the risks and benefits of thrombolysis are uncertain.


To determine whether thrombolysis and reperfusion were beneficial after 4·5 h, we examined clinical and radiological outcomes in patients treated with tissue plasminogen activator or placebo within 4·5–6 h, using data from the Echoplanar Imaging Thrombolytic Evaluation Trial.


In the Echoplanar Imaging Thrombolytic Evaluation Trial, ischemic stroke patients presenting three to six-hours after stroke onset were randomized to tissue plasminogen activator or placebo, without knowledge of magnetic resonance imaging results. This analysis was restricted to patients treated between 4·5 and 6 h. The effect of tissue plasminogen activator and reperfusion on infarct growth between baseline diffusion-weighted imaging and day 90 T2 imaging was assessed, along with good neurological outcome (≥8 point reduction or reaching 0–1 at 90 days on National Institutes of Health Stroke Scale) and functional outcome (modified Rankin scale). The effect of tissue plasminogen activator on reperfusion was also analyzed.


Sixty-nine patients were treated 4·5–6 h after onset, and infarct growth was assessed in 63. Tissue plasminogen activator was associated with lower relative growth (94% vs. 168%, P = 0·03) and a trend to lower absolute growth (−0·17 ml versus 9·6 ml, P = 0·07). Reperfusion was increased in the tissue plasminogen activator group (58% versus 25%, P = 0·03) and was associated with increased rates of good neurological (86% versus 28% P < 0·001) and functional (modified Rankin scale 0–2 73% versus 34%, P = 0·01) outcomes. Reperfusion was strongly associated with lower relative (80% versus 189%, P < 0·001) and absolute (−2·5 ml versus 40 ml, P < 0·001) infarct growth.


Thrombolysis 4·5–6 h after stroke onset reduced infarct growth and increased the rate of reperfusion, which was associated with good neurological and functional outcome.