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Results of six recent trials of endovascular thrombectomy (EVT) for patients with large-core ischemic stroke (LCIS) provide strong evidence for the benefit of this intervention compared with medical management (MM), a new Science Advisory from the American Heart Association (AHA) has concluded.
“These trials provide new data to suggest that selected patients with ischemic stroke due to large vessel occlusions should be treated with EVT,” advisory vice chair Pooja Khatri, MD, professor, vice chair of Research, and director of the Vascular Neurology Division, Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, told Medscape Medical News.
“These findings ran counter to prior thinking and guidelines, so we wanted to bring this important treatment opportunity to the attention of practicing clinicians,” Khatri added.
The Advisory was published online on January 17 in Stroke.
Business News Substantial Clinical Evidence
Until recently, most randomized clinical trials of EVT excluded patients with LCIS. Results from these six new trials are the first dedicated to addressing EVT in LCIS.
LCIS is defined as Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5 on imaging within 6 hours of stroke onset. For patients at 6-24 hours of stroke onset, the definition also includes the CT perfusion scan definition of an area with hypoperfusion volume (cerebral blood flow < 30%) of > 70 cc.
LCIS represents about 25% of ischemic strokes attributable to large vessel occlusion (LVO) among those presenting to referral centers within 8 hours. This, said the advisory authors note, highlights the “substantial clinical relevance” of interventions that could improve outcomes for these patients.
The AHA advisory group searched medical databases for randomized controlled clinical trials (RCTs) published within the past 3 years that compared EVT with MM in patients with an acute ischemic stroke presenting with a large core infarct. The final analysis was based on six RCTs. These included:
- Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan-Large Ischemic Core Trial (RESCUE-Japan LIMIT)
- Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core (ANGEL-ASPECT)
- A Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT2)
- Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke (TESLA)
- The Efficacy and Safety of Thrombectomy in Stroke (TENSION)
- Large Stroke Therapy Evaluation (LASTE).
Business News Greater Likelihood of Ambulation
The trials included a total of 1887 patients, all of whom had major arterial occlusions at the anterior circulation — either the internal carotid artery or middle cerebral artery.
The mean age of participants was mid- to late 60s in trials with upper age limits and mid-70s in the two trials without upper age limits. The median National Institutes of Health Stroke Scale (NIHSS) score of participants ranged from 16 to 22.
Most patients had good pre-stroke functional status with an average modified Rankin Score [mRS] of 0-1.
A total of 78.2% of patients had baseline ASPECTS 3-5, and 16.9% had ASPECTS 0-2. The LASTE trial included a large proportion of patients with very large cores — 56.6% of participants had ASPECTS 0-2.
The minimum NIHSS score for eligibility was 6 in all studies except TENSION, which had no lower limit.
The MRI-based stroke studies consisted of participants primarily in earlier time windows. They were randomized within 6 hours of last known well in RESCUE-Japan LIMIT and 6.5 hours in LASTE.
Among the CT-based studies, TENSION had an intermediate window, randomizing within 11 hours and completing thrombectomy by 12 hours. ANGEL-ASPECT, SELECT2, and TESLA enrolled patients up to 24 hours from the last known well.
The choice of EVT technique, such as stent retriever, aspiration, or both, with or without balloon protection, was at the discretion of the treating physician in all trials. Acute angioplasty, stenting, and intra-arterial thrombolysis were variably permitted.
The primary outcome in all studies was an mRS score at 90 days, which was assessed by blinded assessors. Intravenous thrombolysis candidates received alteplase in all studies.
The authors incorporated adjusted odds ratios (ORs) and their CIs from each study into a unified analysis. The primary analysis produced a combined OR of 1.57 (95% CI, 1.40-1.76).
Higher rates of functional independence were observed after EVT compared with MM in all trials. The difference was most apparent in ANGEL-ASPECT, where 30% of EVT-treated patients achieved functional independence compared with 11.6% of those receiving MM. Other trials showed more modest, but still favorable, results for EVT.
Independent ambulation, which was assessed as part of the Rankin score assessment, was achieved more frequently among those treated with EVT. This was most notable in ANGEL-ASPECT, with 47.0% of patients who received EVT regaining the ability to walk independently vs 33.3% for MM.
Business News ‘Highly Impactful’ Results
After getting these “highly impactful” trial results, “it became very clear that we could probably provide benefit to patients with larger core volumes than previously thought,” Khatri added.
However, it’s still not clear whether those with the very largest core stroke volumes benefit from EVT, said Khatri. She noted the majority of this population was enrolled in LASTE, but this study used MRI selection, which is more sensitive to ASPECT scoring.
“LASTE effectively enrolled those with the equivalent of ASPECTS as low as perhaps 1 or 2 on CT scan. LASTE also only enrolled those with a presumed onset within 6.5 hours, not out to 24 hours as in the other trials.”
To get to better understand if there’s a threshold of ischemic core where EVT doesn’t show benefit, Khatri said the advisory panel “is anxiously awaiting” analyses of patient-level pooled data, which is critical given the disparate designs of the studies.
She said she hopes the principal investigators of the six trials will perform this pooled analysis and release results soon.
“My impression, without the benefit of these pooled data, is that we have not fully tested EVT in patients with the largest cores (ASPECTS 0-2 on CT scan) and certainly not out to 24 hours from onset.”
Pooled data may also “help inform” the generalizability of the results for other subgroups, including the very elderly and later time windows, in addition to those with ultra-large cores, said Khatri.
Across all the trials, symptomatic hemorrhage rates were relatively low, with numerically but not significantly higher rates in EVT groups compared with MM groups. TESLA showed the largest difference, reporting symptomatic hemorrhage rates of 4.0% for EVT compared with 1.3% for MM.
For decompressive craniectomy, the data didn’t indicate a consistent advantage for either treatment approach across trials. As for mortality, outcomes were nominally favorable for EVT in four of the six clinical trials.
Analyzing data on patient quality of life following EVT will be important, said Khatri. “This will help us understand the impact of treatment on quality of life in this population that has overall worse clinical outcomes after stroke.”
There was some concern about bias attributable to deviations from the intended interventions, which occurred in all studies. Overall, protocol violations were limited in number, except in TENSION, which had 25%-30% protocol violations, primarily because of core laboratory ASPECTS values exceeding the intended range in the inclusion criteria.
An update to the AHA 2019 acute ischemic stroke guideline is in process, and publication is expected in early 2026.
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Gaylene Mongold