New study EXTENDs tPA window to 9 hours in select stroke patients

Pearl Toh
21 Feb 2019
New study EXTENDs tPA window to 9 hours in select stroke patients

Patients presenting within 9 hours from stroke onset or with wake-up stroke can still benefit from thrombolytic therapy based on automated computed tomography (CT) perfusion imaging-guided patient selection, according to the EXTEND* study presented at ISC 2019.

“The current guideline for thrombolysis in acute ischaemic stroke is less than 4.5 hours from stroke onset,” said Dr Henry Ma from Monash University in Melbourne, Australia. Thrombolytic therapy is also not usually offered for wake-up stroke as the time of onset is unknown.   

“[However,] advanced imaging studies ... suggest that the ischaemic penumbra can exist up to 24 hours after onset and its salvage can lead to improved clinical outcome,” said Ma.

In the multicentre, double-blind, phase III EXTEND study, 225 patients with ischaemic stroke presenting 4.5–9 hours after onset or with wake-up stroke, who showed salvageable brain tissue on automated CT perfusion imaging, were randomized to intravenous tissue plasminogen activator (tPA) alteplase 0.9 mg/kg or placebo. A significant penumbral mismatch on imaging indicates salvageable brain tissue which is severely hypoperfused but not yet infarcted. [ISC 2019, LB21]  

Patients treated with tPA achieved significantly better functional outcomes than the placebo group at 3 months, as indicated by mRS 0–1 (35 percent vs 29 percent, adjusted risk ratio [aRR], 1.44; p=0.042) and mRS 0–2 (50 percent vs 28 percent, aRR, 1.73; p=0.002) in the intention-to-treat population.

Similar results were obtained in the per-protocol analysis (37 percent vs 29 percent, aRR, 1.45; p=0.045 for mRS 0–1), which included 65 percent of patients presenting with wake-up stroke.

Early neurological improvement (NIHSS** reduction 8 points or 0–1 at 24 hours; 25 percent vs 10 percent, aRR, 2.67; p=0.002) and early reperfusion of 90 percent at 24 hours (51 percent vs 28 percent, aRR, 1.78; p=0.001) were also better in the tPA group vs the placebo group.

Although there was more incidence of symptomatic intracranial haemorrhage (sICH) at 36 hours among patients receiving tPA (6 percent vs 1 percent, aRR, 6.48; p=0.066), mortality rates were similar between the two groups (11.1 percent vs 9.5 percent, aRR, 1.03; p=0.77).

“[The] increase in the rate of sICH [was] consistent with other thrombolytic trials, but this was not associated with increased mortality and did not negate the positive result of improved rate of excellent functional outcome,” Ma pointed out.

EXTENDed benefit

The findings provide further support that the time window for tPA treatment can be extended beyond the recommended 4.5 hours in certain patients selected based on tissue imaging, he said.

The previous WAKE-UP trial showed that tPA can benefit patients with wake-up stroke >4.5 hours before treatment, but unlike the current study, the WAKE-UP trial selected patients using magnetic resonance imaging (MRI).

“EXTEND is the first positive thrombolysis trial in an extended time window using automated penumbral imaging,” said Ma, who noted that CT perfusion imaging is more readily available than MRI in many stroke centres.

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