Late-Presenting Stroke: Who Benefits from Thrombectomy?

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RESEARCH UPDATE

Receiving a thrombectomy to remove a blood clot up to 16 hours after stroke onset may benefit a broad range of patients who have evidence of salvageable brain tissue, according to findings from the DEFUSE 3 trial.¹

Results showed that the procedure benefited very old as well as younger patients, those with mild to severe stroke, and those with internal carotid artery (ICA) or middle cerebral artery (MCA) strokes. Results also suggested that both CT and MRI can be used to select patients for thrombectomy, with no significant difference in outcomes. The study was published in JAMA Neurology.¹

“Endovascular therapy should not be withheld because of old age, mild symptoms, or late presentation in patients with large-vessel strokes and salvageable tissue on computed tomography or magnetic resonance imaging,” wrote first author Maarten Lansberg, MD, PhD, of Stanford University School of Medicine (Stanford, CA), and colleagues.

Studies have established the efficacy of thrombectomy for treating ischemic stroke within six hours of onset. Results from both the DAWN trial and the DEFUSE 3 trials extended this time window for certain patients.^2,3

That led the American Heart Association/American Stroke Association to revise their guidelines to recommend thrombectomy up to 16 hours after stroke onset (high quality evidence) as well as within the 16- to 24-hour time window (moderate quality evidence).⁴

But that left the question whether the procedure benefits some patients more than others.

To evaluate the efficacy of thrombectomy in different patient groups, researchers conducted a secondary analysis of the larger DEFUSE 3 study. DEFUSE 3 was a randomized, open-label blinded trial that took place at 38 sites in the US between from May 2016 to May 2017. It included 296 individuals with acute ischemic stroke caused by a blood clot in the internal carotid artery or middle cerebral artery.

To be included, patients had to have evidence of salvageable brain tissue on perfusion CT or MRI. Researchers randomized participants to endovascular therapy plus medical management or medical management alone. The trial was stopped early when thrombectomy was clearly shown to be more effective than medical management alone.

The secondary analysis included 182 patients from the larger trial. Efficacy of thrombectomy from stroke onset was evaluated in a smaller subset of 66 patients for whom stroke onset was known.

Results adjusted for age, stroke severity and blood glucose levels showed that thrombectomy performed up to 16 hours after the last known well time was linked to three times improved functional outcome at 90 days (adjusted OR 3.12, 95% CI 1.81-5.38, p<0.001).

Age (23-90 years, p=0.93), stroke severity (p=0.87), time to procedure (6-16 hours, p=0.56), location of blood clot (ICA or MCA, p=0.54), and whether the patient was selected for therapy using CT or MRI (p=0.49) did not affect results.

However, in both groups the probability of being functionally independent 90 days after stroke onset decreased with increasing age, increasing stroke severity, and increasing time since stroke onset to thrombectomy. 

So, while the proportional benefit of thrombectomy was similar across a wide range of patients and did not differ based on whether CT or MRI was used to select patients for the procedure, the absolute treatment benefit was smaller for older individuals.

However, the authors emphasized: “[A]dvanced age, up to 90 years, should not be considered a contraindication to thrombectomy, provided that the patient is fully independent prior to stroke onset.”

They note that the results contrast with other studies that have suggested worse outcomes with longer onset to procedure times. Those studies included more patients with rapidly expanding ischemic cores, where blood flow is severely restricted and brain cells may have already died. In contrast, the DEFUSE 3 study included a majority of patients with slow growing ischemic cores, for whom treatment delays may not substantially affect outcomes.

Despite these differences, the authors urged providers to treat individuals with late-presenting stroke with equal urgency as early presenters.

The authors noted that the study was small, and that further study is needed to confirm the results.

Take Home Points
• Secondary analysis of the DEFUSE 3 trial showed that thrombectomy up to 16 hours after stroke onset was linked to three times improved functional outcome at 90 days in patients with ischemic stroke and salvageable brain tissue, compared to medical management alone
• Results were not significantly affected by age, stroke severity, time to procedure, or location of blood clot (ICA or MCA)
• Using CT vs MRI to select patients for thrombectomy did not significantly affect outcomes

References:

1. Lansberg MG, Mlynash M, Hamilton S, et al. Association of Thrombectomy With Stroke Outcomes Among Patient Subgroups: Secondary Analyses of the DEFUSE 3 Randomized Clinical Trial. JAMA Neurol. 2019 Jan 28. [Epub ahead of print]
2. Nogueira RG, Jadhav AP, Haussen DC, et al; DAWN Trial Investigators. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378:11-21.
3. Albers GW, Marks MP, Kemp S, et al; DEFUSE 3 Investigators. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378:708-718. doi:10.1056/NEJMoa1713973
4. Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Stroke Council. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e110.