Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke
Ma H, Campbell BCV, Parsons MW, et al. N Engl J Med. 2019;380:1795-1803.
SUMMARY:
Medical and endovascular treatment of stroke, largely driven by improved neuro-imaging, is undergoing rapid change. Cerebral perfusion imaging techniques such as RAPID software show how much of a stroke territory is dead tissue (the infarcted core) and how much of it is stunned tissue (ischemic penumbra). Previous work has fairly convincingly shown that patients who have the right size of stroke and ratio of ischemic tissue to core tissue, and have large-vessel occlusion, benefit from endovascular therapy (EVT).
Tissue plasminogen activator (tPA) is indicated for acute debilitating stroke if the last well time is < 4.5 h. The research question here is whether tPA would benefit people whose last well time is up to 9 h before presentation if they have favorable ischemic-to-core ratios.
This was a multicenter RCT of tPA versus placebo, which was conducted primarily in Australia. This trial was not directly sponsored by a drug company but was sponsored by the Australian National Health and Medical Research Council. Eligible patients were required to have stroke symptoms for 4.5-9 h, good prestroke functional status (modified Rankin score (mRs) 0 or 1), and favorable CT or MRI perfusion studies, and to not be under consideration for EVT. The primary outcome was mRs of 0 or 1 at 90 d (ie, being able to perform all activities of daily living with minimal help). There were multiple secondary outcomes related to reperfusion, recanalization, and changes in the NIH Stroke Scale. The key safety outcome was brain bleeding.
The study was terminated early, after enrolling only 225 of 310 anticipated patients (113 alteplase and 112 placebo).
The study had a drawback of a failure of randomization. Overall, the alteplase group was sicker than the placebo group at baseline, but the alteplase group fared slightly better: 35% had good neurological outcomes, compared with 29.5% in the placebo group, but this result was statistically nonsignificant. The authors then adjusted for baseline stroke severity, and the results scarcely reached statistical significance: AOR 1.44 (CI 1.01-2.06, P = .04). Most of the secondary results showed the same pattern.
One finding that was clearly different was the bleed rate of 6.2% in the alteplase group versus 0.9% in the placebo group.
The authors stopped this trial early because most patients had large-vessel occlusion, and various studies showed in 2018 that EVT is a better approach for patients with stroke.
EDITOR’S COMMENTARY: This is a relatively well conducted RCT that did not show convincing evidence that IV tPA should be used for patients beyond 4.5 h, even if they have favorable ischemia-to-infarct ratios on CT scanning. The intracerebral hemorrhage rate is higher, and the functional outcomes are basically the same. EVT should be pursued in this group if applicable.
Copyright 2019 by Emergency Medical Abstracts – All Rights Reserved 09/19 - #02
Ian L. - September 5, 2019 2:33 PM
If they knew EVT was going well I cannot but worry about the 6% intracranial Hemorrhage rate .
And over 200 collaborators .!