Outcomes were not compromised even in those treated up to 6 days after last known well, a retrospective study found.
Endovascular thrombectomy can be safely used in select patients with anterior circulation large vessel occlusion (LVO) beyond 24 hours from time last known well, according to the results of a small, retrospective review published in the Journal of NeuroInterventional Surgery.
Previously, the DAWN trial reported better outcomes for thrombectomy plus standard medical care than standard medical care alone in patients with acute stroke presenting between 6 and 24 hours.
“Prior to DAWN, for patients presenting beyond 6 hours, there were no randomized trial data to support a benefit in a later time window,” said senior author Ashutosh P. Jadhav, MD (University of Pittsburgh Medical Center, PA). “After DAWN we had the first study to compare thrombectomy versus medical management in that population and data to support treating people in the 6-to-24-hour window.”
What the so-called “beyond DAWN” study shows, Jadhav told Neurovascular Exchange, is that timelines may be a bit arbitrary.
“Why 6 hours? Why 12 hours? Why 24 hours? Everyone has a different biological clock in how quickly neurons die when there is a blockage,” he said. “It looks like there is a population that benefit even in the later time windows.”
Opening the Window
For the new retrospective review study, researchers compared outcomes in selected patients who met DAWN criteria and who received thrombectomy beyond 24 hours (n = 21) and those treated between 6 and 24 hours in the thrombectomy arm of the DAWN trial (n = 107).
The 21 review patients were treated at three tertiary care medical centers in the United States. All were treated beyond 24 hours since time last known well, had intracranial ICA or first segment of MCA occlusion with or without extracranial occlusion, and had age-based mismatch between clinical severity of stroke and infarct core volume, and a baseline mRS score of 0-1.
Successful reperfusion occurred in 81% of patients treated beyond 24 hours compared with 84% of patients treated within 24 hours in the DAWN trial. The 90-day functional independence (mRS 0-2), was 43% for those treated beyond 24 hours versus 48% in the DAWN trial. Finally, symptomatic intracranial hemorrhage occurred in 5% of patients treated beyond 24 hours and in 6% of patients enrolled in DAWN. Mortality rates also were the same at 19% in both groups.
“The good news is that even though the [randomized] trials went to 16 or 24 hours, if you are selecting patients carefully using the same imaging criteria [as the trials] you can still help people with this therapy if they come at 30 or 40 hours, or even days out,” Jadhav said. “There are biologically slow progressors where the stroke progresses very slowly and despite the blockage, there is still a lot of brain tissue we can save.”
Clinical Implications
Jadhav and colleagues noted that of the 16 patients that presented with anterior circulation LVO during the DAWN trial enrollment period at the University of Pittsburgh Medical Center, five underwent thrombectomy beyond 24 hours past time last known well but also met all other DAWN criteria.
These patients accounted for 0.2% of all acute ischemic stroke admissions during the trial enrollment period. Jadhav and colleagues also recently reported that about 1.7% of patients with acute ischemic stroke presenting to a comprehensive stroke center met criteria for DAWN. Therefore, combined, 1.9% of all patients presenting met DAWN criteria beyond 6 hours since time last known well, representing an increase in thrombectomy eligibility.
Whether the results of the “beyond DAWN” study will change treatment paradigms will be variable since some centers are much more guideline driven than others and are very specific about how they manage patients, Jadhav said.
“There are places that, before the results of DAWN or DEFUSE-3, if a patient presented beyond 6 hours they did not offer endovascular therapy because the guidelines, before this year, were specific about it being Class Ia evidence,” he said. “But there is also an evidence-based approach and physiology-based approach that may be relevant to a subset of the population.”
The reality is though, Jadhav noted, that researchers will not likely ever be able to do a large randomized trial of patients presenting beyond 24 hours because it is such a small population.
“The best we can do is look at registry data or retrospective studies,” Jadhav said. “We are not going to have Class 1a evidence that addresses this question.”
Sources:
Desai SM, Haussen DC, Aghaebrahim, et al. Thrombectomy 24 hours after stroke: beyond DAWN. J NeuroIntervent Surg. 2018;Epub ahead of print.
Disclosures:
Jadhav reports no relevant conflicts of interest.
