Reperfusion thrombolysis window depends on imaging

There is now more evidence to support recent Australian stroke guidelines update that extended the window of opportunity for thrombolysis from 4.5 to 9 hours in patients who meet perfusion mismatch criteria.

A meta-analysis of the EXTEND and EPITHET RCTs, published in JAMA Neurology, has shown the benefits and risks of thrombolysis-induced reperfusion are consistent across the time windows of 4.5 to 6 hours, 6 to 9 hours, and in wake-up stroke patients.

Together the two trials included 295 patients with CT or MR perfusion-diffusion mismatch.

The meta-analysis found alteplase was associated with significantly increased reperfusion versus placebo (51% v 28%; RR 1.84; p <0.001)

“In each of the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata, reperfusion was associated with significant improvements in ordinal analysis of mRS score, mRS score of 0 to 2, and early neurological improvement, but the 95% CI crossed unity for mRS score of 0 to 1 in the 6- to 9-hours group,” the study said.

“There was no evidence of differential risk of symptomatic intracerebral haemorrhage in these strata.”

Lead author on the study Professor Bruce Campbell told the limbic that a 2019 meta-analysis published in The Lancet was the key step in changing Australia’s guidelines late last year.

“The reperfusion paper just published improves our confidence that the benefits apply right across the eligible time window used in the studies.”

Professor Campbell, Head of Stroke at the Royal Melbourne Hospital, said implementation was however patchy.

“Across Victoria I think we are very well served with a telemedicine service that is centralised and everyone knows about this and people out in the country do the perfusion imaging.”

“In the US, they have great difficulty implementing anything more complicated than a non-contrast CT outside the big cities.”

He said the feedback from some overseas colleagues had previously been “Are you sure?”

“This was one way to shore up that confidence in the data.”

He emphasised that selection of patients with favourable perfusion imaging was critical.

“And the important messaging for the community is we do not have 9 hours to get thrombolysis in. Every second counts. The proportion of people who are eligible for this kind of treatment drops off rapidly with time.”

“Within 4.5 hours we treat everyone,” he said.

However in a consecutive series of patients at Royal Melbourne Hospital, excluding people with poor pre-stroke function and very mild presentations who would not be candidates for clot-dissolving medication, only 51% of patients who presented to hospital in the 4.5-9 hr/wake-up onset time window met the imaging criteria that indicate salvageable brain tissue.

Professor Campbell added that there was an ongoing Australian-led trial trying to push that time window out to 24 hours using tenecteplase which may be a more effective clot-dissolving agent.

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