WAKE-UP: more certainty with thrombolysis in lacunar stroke


By Mardi Chapman

3 Apr 2019

Intravenous alteplase appears to be as effective in patients with lacunar stroke as it is in patients with nonlacunar stroke.

A post hoc analysis of the WAKE-UP trial data (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), found 108 of the 503 patients (21.5%) had a lesion consistent with lacunar infarct on MRI.

Of the patients with lacunar infarct, slightly more patients who received alteplase had a favourable outcome at 90 days – defined as 0-1 on the modified Rankin Scale – than those who received placebo (59% v 46%, p=0.2).

However only treatment response, a secondary end point, was statistically better with alteplase than placebo (36% v 14%, p=0.009).

Among the full cohort of patients with both lacunar and nonlacunar infarcts, treatment with alteplase was associated with a higher odds ratio of favourable outcome regardless of stroke subtype (OR 1.61 overall, 1.68 lacunar, 1.62 nonlacunar).

“As a main result, we found no evidence of heterogeneity of the treatment outcome with regard to stroke subtype (ie, lacunar or nonlacunar infarct). Thus, our data suggest that treatment with alteplase is of similar benefit in patients with lacunar infarcts as in those with other stroke subtypes,” the researchers said.

Death or dependence rates were similar in both groups (8%) and there was one symptomatic intracranial haemorrhage in the alteplase group.

The researchers noted that the WAKE-UP trial was not powered to demonstrate treatment outcome in sub groups of patients.

An editorial in JAMA Neurology said that, despite its limitations, the study ‘further tips the scales strongly in favour of treating lacunar strokes’.

However the editorial also raised the issue of imaging modality in patient selection for thrombolysis.

“Even in high-income countries, most hospitals that receive patients with strokes do not have expeditious access to MRI. The primary results of the WAKE-UP trial provide definitive data that the availability of rapid MRI will allow clinicians to use thrombolysis to provide a meaningfully improved clinical outcomes for an additional population of patients.”

A co-author on the study Professor Vincent Thijs, from the Florey Institute, agreed that around the world CT and CT perfusion rather than MRI were used to make treatment decisions. Yet lacunar stroke doesn’t show up as well on CT perfusion scans as on MRI.

“At least in a sub group of patients that wake up with stroke and have a lacunar syndrome, thrombolysis is still beneficial, and at the moment that can only be identified by doing a MRI.”

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