Abstract 61: Reperfusion Beyond 4.5 Hours Reduces Infarct Growth And Improves Clinical Outcome
Background and purpose: The ECASS 3 study demonstrated efficacy of intravenous thrombolysis up to 4.5h after stroke onset. It has been hypothesized that some patients have tissue at risk and an acceptably low hemorrhage risk beyond 4.5h. Imaging based selection may help identify these patients for late reperfusion therapies. No randomized data have shown efficacy of tPA or reperfusion later than 4.5h after onset. We analysed the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) data to assess the effect of treatment and reperfusion on attenuation of infarct growth in the 4.5 to 6 hour time window.
Methods: Patients were randomized to placebo or tissue plasminogen activator (tPA) between 4.5-6h from stroke onset (without using imaging selection criteria). Pre-treatment DWI and day 90 T2-weighted lesion volumes (average of manually outlined lesions by 2 independent raters) were compared to assess the influence of tPA and reperfusion on absolute and relative infarct growth. Day 3 volume was used when day 90 data was missing. The effect of tPA on reperfusion was also assessed. Good clinical outcome was defined as a National Institute of Health Stroke Scale (NIHSS) at day 90 0-1 or improvement ≥ 8 from baseline. Good functional outcome was defined as modified Rankin Scale (mRS) 0-2.
Results: Of 69 patients treated 4.5-6hrs hours after stroke onset, infarct growth could be assessed in 63. The median relative growth was significantly lower in the tPA group compared to placebo (0.94 vs 1.68, p=0.025). There was a nonsignificant trend towards lower absolute growth (-0.17mL vs 9.56mL, p=0.069). Reperfusion markedly reduced relative (0.80 vs 1.89, p<0.001) and absolute infarct growth (-2.49mL vs 39.50mL, p<0.001). Reperfusion was more likely in the tPA group (57.7 vs 25.0% p=0.026) and was associated with better clinical and functional outcomes (86.4% vs 28.1% p<0.001 and 72.7 vs 34.4% p=0.012).
Conclusion: Thrombolysis after 4.5 hours reduced infarct growth and increased the rate of reperfusion. The strong positive effect of reperfusion on clinical and functional outcomes in this later time window is evidence of persisting salvageable ischemic penumbra. This supports continuing efforts to extend the treatment window for reperfusion therapies.
- © 2012 by American Heart Association, Inc.