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MRI-guided thrombolysis can reduce likelihood of disability in patients with stroke of unknown symptom onset (WAKE-UP)
Clinical Question
In patients with an unknown time from symptom onset but favorable characteristics on magnetic resonance imaging, does thrombolysis provide a net benefit?
Bottom line
In patients with stroke and an unknown time from symptom onset, using magnetic resonance imaging (MRI) to identify a subset who are likely to be within 4.5 hours of onset was successful at increasing the likelihood that a patient would have a good outcome from thrombolysis. However, deaths were also more common in the intervention group, so there is a definite trade-off: a better chance at independence, but an also somewhat greater chance of dying. If this is applied in the community, it will be important that clinicians use the precise MRI criteria described in this study to avoid increasing harm. 1b
Reference
Study design: Randomized controlled trial (double-blinded)
Funding: Government
Setting: Inpatient (any location) with outpatient follow-up
Synopsis
Thrombolysis is generally limited to patients who are no more than 4.5 hours from symptom onset. When a patient awakens with symptoms, they are generally not candidates for thrombolysis since the stroke could have occurred early in the sleep cycle. However, patients within 4.5 hours of symptom onset can potentially be identified via MRI, since they usually have a visible ischemic lesion and no hyperintense signal on fluid-attenuated inversion recovery imaging. This study identified 503 adults with acute stroke and no previous disability who had unknown timing of symptom onset. Their mean age was 65 years (patients older than 80 years were excluded), 65% were men, the mean National Institutes of Health Stroke Scale score was 6 points, and 95% had awoken from sleep with their symptoms. They were randomized to alteplase or placebo infusion, and followed up for 90 days. Analysis was by intention to treat, and groups were balanced at the beginning of the study. The sample size was lower than the targeted 800 patients because of loss of funding from the European Union. The primary outcome was a favorable outcome defined as a modified Rankin score of 0 or 1 at 90 days, indicating no significant disability, and was more likely in the intervention group (53% vs 42%; P = .02, number needed to treat = 9). Secondary outcomes such as quality of life and depression were also consistently better in the intervention group. The combined outcome of death or inability to live independently was less likely (nonsignificantly) in the intervention group (13.5% vs 18.3%; P = .17). However, there were more deaths in the intervention group, again nonsignificantly (10 vs 3; P = .07).
Reviewer
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Comments
tPA is bad for stroke. Only one weak study has shown benefit.
THIS WAS VERY INTERESTING FOR ME MRI TAKES 1/2 TO 1 HOUR PERFORM THAT INCREASE TIME.
IT WILL BE NICE WHAT WAS REASON FOR INCREASED DEATH AND IF THAT CAN BE AFFECTED BY DOSAGE OF MEDICATION GIVEN
Risks appear high in treatment group compared to a modest benefit. There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P=0.07). The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P=0.15).
good poem
interesting concept. potentially very beneficial if proper MRI interpretation