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Stroke patients presenting beyond the 4.5-hour window had consistent benefits from tissue plasminogen activator (tPA) when there was evidence of perfusion mismatch, researchers found from the EXTEND and EPITHET trials.

People who achieved reperfusion with IV alteplase (Activase) administration at 24-72 hour follow-up were found to have better functional outcomes at 90 days (common OR 7.7 against peers without reperfusion, 95% CI 4.6-12.8), an individual patient-level pooled analysis of the two trials showed.

This was consistent across subgroups presenting 4.5 to 6 hours or 6 to 9 hours after symptom onset or after wake-up stroke, with no evidence of interaction between time to randomization and beneficial effect of reperfusion, according to Bruce Campbell, PhD, of Royal Melbourne Hospital in Australia, and colleagues reporting online in .

Symptomatic intracerebral hemorrhage (SICH) risk didn't differ across later times to treatment either, as alteplase recipients showed incidence rates of 5.9% in the 4.5-6 hours group, 7.1% in the 6-9 hours group, and 5.5% in the wake-up stroke group.

"This provides reassurance that the benefits of IV alteplase are also likely to be consistent across the strata in patients with perfusion mismatch," Campbell's group concluded.

"Further trials will test whether IV thrombolysis can benefit patients with perfusion mismatch up to 24 hours after the time they were last known to be well," the authors noted.

Previous work had suggested that IV alteplase reduces disability after ischemic stroke in patients 4.5-9 hours after onset (or with wake-up onset stroke) selected using perfusion imaging mismatch. Such patients are normally considered ineligible for thrombolysis based on the 4.5-hour standard window.

and were two randomized trials performed in 2001-2018.

Campbell's team included the 295 patients who were randomized to alteplase or placebo after perfusion mismatch imaging 4.5-9 hours after acute ischemic stroke onset. Of these patients, 270 had reperfusion assessable.

Median age was 76 years in the reperfusion group and 74 years in the group with no reperfusion. Men accounted for 46.2% and 61.0%, respectively; and median baseline National Institutes of Health Stroke Scale scores were 10 and 12, respectively.

A limitation of the meta-analysis was that true stroke onset time was often unknown in the two trials.

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