Breaking the time barrier: perfusion imaging extends alteplase treatment


By Mardi Chapman

9 May 2019

The window of opportunity for treating stroke with thrombolysis can be doubled from 4.5 hours to 9 hours from symptom onset or awakening with stroke.

The EXTEND trial, led by Australian researchers and published in the New England Journal of Medicine, randomised 225 patients with acute ischaemic stroke to either alteplase or placebo at a time period between 4.5 and 9 hours.

Inclusion criteria included hypoperfused but salvageable regions of the brain detected on automated perfusion imaging with CT or MRI.

The study was conducted at 16 centres in Australian, New Zealand, Taiwan and Finland.

It found the primary outcome – a score of 0-1 on the modified Rankin scale at 90 days – was attained by 35.3% of patients treated with alteplase compared to 29.5% of patients who received the placebo (adjusted risk ratio, 1.44; 95% confidence interval, 1.01 to 2.06; p=0.04).

Mortality at 90 days was similar in both groups (11.5%v 8.9%; p=0.67) while symptomatic intracranial haemorrhage (ICH) was higher in the treated group (6.2% v 0.9%, p=0.053).

The researchers said the findings would change the way stroke is managed and particularly for patients outside metropolitan areas. It could be used to treat people with delayed presentation before transfer to comprehensive stroke centres for thrombectomy.

Lead author Associate Professor Henry Ma told the limbic the advance was driven by perfusion imaging that allowed clinicians to identify areas of the brain that could still be salvaged.

“This will increase substantially the number of patients who will benefit. In Australia it will increase by about 50% the number of patients we can treat.”

Associate Professor Ma, from Monash Health, Melbourne, said the increase in ICH, bordering on statistical significance, was known to be a major complication from thrombolysis.

“But our haemorrhage rate is exactly the same as every other thrombolysis trial and late-time thrombectomy trial so we think the risk of haemorrhage is outweighed by the benefit of the treatment.”

“We are very confident it is better – to get someone back home with their family and without disability.”

An accompanying editorial in NEJM said the era of time-based treatment with intravenous alteplase may be drawing to a close.

“The success of this trial is attributable to an image-guided approach to patient selection that had already brought success to mechanical thrombectomy performed many hours after the onset of stroke symptoms.”

“While thrombolysis was stuck in a time window of 4.5 hours, remarkably good outcomes with thrombectomy were being shown at 6 hours, 16 hours and 24 hours.”

It said one of the clinical implications was that stroke centres with the capacity to identify suitable patients, could now treat patients with delayed presentation without the need for an interventionalist.

“Furthermore, because the image analysis software is available commercially and is automated for computed tomography and magnetic resonance imaging, primary stroke centres could provide this service.”

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