Reperfusion after 4.5 hours reduces infarct growth and improves clinical outcomes

Abstract

Background: The currently proven time window for thrombolysis in ischemic stroke is 4.5 h. Beyond this, the risks and benefits of thrombolysis are uncertain.

Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: MRI; stroke; tPA; thrombolysis.