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EXTEND: Initiating alteplase after traditional treatment window may reduce neurologic deficits
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Patients with salvageable brain tissue who were assigned alteplase between 4.5 and 9 hours after the onset of an ischemic stroke or when they woke up with stroke symptoms were more likely to have no or minor neurologic deficits compared with those assigned placebo, according to a phase 3 trial published in The New England Journal of Medicine.
Acute ischemic stroke
Henry Ma, PhD, adjunct senior lecturer at Monash University in Melbourne, Australia, and colleagues analyzed data from 225 patients with acute ischemic stroke and who had salvageable regions of the brain on automated perfusion imaging.
Researchers originally planned to enroll 310 patients, but recruitment was stopped because of loss of equipoise after results of the WAKE-UP trial were published. As Cardiology Today previously reported, among patients with acute stroke of unknown time of onset but MRI findings indicating onset was recent, IV thrombolysis with alteplase resulted in a better functional outcome than treatment with placebo.
“The positive results of the WAKE-UP trial drove the decision to terminate the current EXTEND trial; however, the patient population and imaging selection differed in the two trials,” Ma and colleagues wrote. “The clinical severity of stroke was milder in the WAKE-UP trial, with a median NIH [Stroke Scale] score of 6, and the MRI-based selection model aimed to identify patients with stroke onset within the standard 4.5-hour thrombolysis window.”
Patients were assigned alteplase (n = 113; mean age, 74 years; 52% men) or placebo (n = 112; mean age, 71 years; 59% men). Both treatments were administered between 4.5 and 9 hours after stroke onset or upon awakening with stroke.
The primary outcome of interest was a modified Rankin scale score of 0 or 1 at 90 days. The RR for this outcome was adjusted for clinical severity of stroke and age at baseline.
The primary outcome occurred in 35.4% of patients assigned alteplase and 29.5% of those assigned placebo (adjusted RR = 1.44; 95% CI, 1.01-2.06). Symptomatic intracranial hemorrhage was seen in 6.2% of the alteplase group vs. 0.9% of the placebo group (aRR = 7.22; 95% CI, 0.97-53.5).
There was no significant between-group difference for functional improvement at 90 days (common OR = 1.55; 95% CI, 0.96-2.49).
“Because of the limited power of our conclusions as a result of premature termination of the trial and the lack of a significant between-group difference in the secondary outcome of functional improvement, further trials of thrombolysis in this time window are required,” Ma and colleagues wrote.
Clinical implications
“Extending the time window for treatment could result in greater numbers of patients eligible to receive treatment for acute stroke,” Randolph S. Marshall, MD, MS, Elisabeth K. Harris Professor of Neurology at Columbia University College of Physicians and Surgeons, and chief of the stroke division and attending neurologist on the stroke service at NewYork-Presbyterian Hospital, wrote in a related editorial. “Perhaps more importantly, stroke centers with imaging capability to detect a mismatch between the size of the ischemic core and the penumbra could treat patients with stroke many hours after the onset of stroke symptoms and treat those who awaken with a stroke, without the need for an interventionalist to be present.” – by Darlene Dobkowski
Disclosures: Boehringer Ingelheim provided the alteplase and placebo used in this trial. ISchemaView provided a research version of software used in the trial for free. Ma and Marshall report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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