MedWire News: The use of mismatch imaging to identify patients who will benefit from delayed thrombolysis is a promising strategy but requires validation in a phase III trial, say the authors of a meta-analysis.

Writing in the journal Stroke, they say that delayed thrombolysis in patients with perfusion/diffusion mismatch on pretreatment imaging is associated with improved reperfusion and recanalization.

However, pending the results of a large randomized controlled trial, “delayed treatment, even according to mismatch selection, cannot be recommended as part of routine care,” write Kennedy Lees (University of Glasgow, UK) and co-authors.

For the study, Lees et al searched the literature for thrombolysis treatment trials in which patients were enrolled 3 hours or more after the onset of stroke symptoms. All patients had mismatch on pretreatment magnetic resonance imaging, defined as a perfusion volume at least 1.2 times that of the infarct core.

The meta-analysis included a total of 5 randomized controlled trials and 502 patients who received delayed thrombolysis or matching placebo.

A favorable outcome (defined as a National Institutes of Health Stroke Scale [NIHSS] score increase of 8 points versus baseline or attainment of a NIHSS score of 0 or 1 and/or a modified Rankin Scale score of 0 or 1) was more likely in patients who underwent successful reperfusion (adjusted odds ratio [AOR]=5.2) than in those who did not, Lees and colleagues report.

Furthermore, successful reperfusion or recanalization was more likely in patients who received thrombolytic therapy (AOR=3.0), although the likelihood of a favorable outcome was not significantly increased by receipt of thrombolysis (AOR=1.3).

With regard to safety, the risks for mortality and symptomatic intracerebral hemorrhage were significantly increased in patients who received thrombolysis (AORs=2.4 and 6.5, respectively).

However, these risk increases were no longer significant after excluding patients who received doses of desmoteplase that were later discontinued from clinical development (AORs=1.6 and 5.4, respectively).

Discussing their findings, Lees et al say that delayed thrombolysis in mismatch patients “was not confirmed to improve clinical outcome, although a useful clinical benefit remains possible.” They also note that the criteria to diagnose mismatch “are still evolving.”

A prospective phase III trial, EXTEND (EXtended time for Thrombolysis in Emergency Neurological Deficits), is now underway in Australia, randomizing patients 4.5 to 9 hours after stroke onset to alteplase or placebo, using automated mismatch selection.

“Meanwhile, although the concept of selection of patients based on individual pathophysiology rather than a rigid time window remains attractive, delayed treatment according to mismatch selection cannot be recommended as part of routine care until or unless further trials show benefit.”

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