Stroke: Thrombolysis Guided by Perfusion Imaging Extended Time Window up to 9 Hours after Onset Interview with:

Geoffrey A Donnan AOMBBS, MD, FRCP, FRACP, FAAHMSProfessor of NeurologyUniversity of Melbourne, Melbourne Brain Centre,Royal Melbourne and Austin Hospitals

Prof. Donnan

Geoffrey A Donnan AO
Professor of Neurology
University of Melbourne, Melbourne Brain Centre
Royal Melbourne and Austin Hospital What is the background for this study? What are the main findings? 

Response: Currently the thrombolysis time window for acute ischemic stroke is restricted to less than 4.5 hours from stroke onset and patients with wake-up stroke are not eligible.

EXTEND is a multi-centre randomised placebo-controlled trial involving patient with acute ischemic stroke who presented between 4.5 to 9 hours of stroke onset or with wake-up-stroke and had penumbral tissue demonstrated on automated perfusion imaging.

Patients were randomised to receive either alteplase or placebo. In total there were 225 patients recruited and the patients who received alteplase had higher rate of excellent functional outcome at 3 months (35.4% vs 29.5% adjusted odd ration 1.44 with 95% confidence interval 1.01 – 2.06 p=0.04). Patients who received alteplase achieved higher rate of early neurological improvement at day 3, reperfusion and recanalization at 24 hours. There was numerically more haemorrhage in the alteplase group but this not negate the functional benefit and there was no difference in the rate of mortality between the two groups. What should readers take away from your report?

Response: Acute ischemic stroke patients who present in the extended time window of 4.5 to 9 hours from stroke onset or wake-up stroke with perfusion mismatch on automated perfusion imaging can achieve higher rate of excellent functional outcome with alteplase compared to placebo. This is the first positive trial extending the thrombolysis time window, hence it is time to consider thrombolytic therapy beyond 4.5 hours from stroke onset and in patients with wake up stroke. What recommendations do you have for future research as a result of this work?

Response: It is important to consider extend the thrombolytic time window up to 24 hours from stroke onset with a potentially more effective thrombolytic agent such as tenecteplase. It is crucial to use perfusion imaging to select an enriched cohort of patients who may respond to thrombolytic therapy in this time window.

No disclosures


Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke

Henry Ma, Ph.D., Bruce C.V. Campbell, Ph.D., Mark W. Parsons, Ph.D., Leonid Churilov, Ph.D., Christopher R. Levi, M.B., B.S., Chung Hsu, Ph.D., Timothy J. Kleinig, Ph.D., Tissa Wijeratne, M.D., Sami Curtze, Ph.D., Helen M. Dewey, Ph.D., Ferdinand Miteff, M.B., B.S., Chon-Haw Tsai, Ph.D., et al., for the EXTEND Investigators*
May 9, 2019
N Engl J Med 2019; 380:1795-1803
DOI: 10.1056/NEJMoa1813046




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