Stroke Snapshot: Endovascular Thrombectomy for Stroke Treatment Outside the Established Criteria for Efficacy

Large vessel occlusion (LVO) strokes constitute more than 25% of all ischemic strokes and are the most debilitating among them.¹ Landmark randomized controlled trials (RCT) have demonstrated unequivocally improved clinical outcomes through the use of endovascular thrombectomy (EVT) for treatment of LVO strokes, and EVT is the standard treatment under specific conditions. According to American Heart Association treatment guidelines, last updated in 2019,² it is strongly recommended (class 1A) that adults with a causative occlusion of the internal carotid artery or middle cerebral artery M1 segment undergo emergent EVT with stent retriever as long as there is no prestroke disability (modified Rankin Scale [mRS] score 0 to 1), disabling neurologic deficits are present (National Institutes of Health Stroke Scale [NIHSS] score ≥6), large infarcted core is absent (Alberta Stroke Program Early CT Score [ASPECTS] ≥6), and EVT can be initiated within 6 hours of symptom onset. For people experiencing symptoms within 6 to 24 hours, additional imaging criteria (eg, a mismatch between hypoperfused and infarcted tissue) must be met.²

Despite the demonstrated benefits of EVT in selected populations, a substantial proportion of people with LVO are not considered eligible candidates or are perceived as being at increased risk from the procedure. This subset comprises individuals with a substantial infarcted core upon presentation, mild neurologic deficits, or preexisting disability. In addition, studies regarding the effectiveness of EVT in LVO caused by basilar artery occlusion (BAO) initially yielded inconsistent results. As a consequence of the incomplete evidence, current guidelines lack definitive recommendations for treating these individuals. The objective of this short review is to assess emerging evidence regarding the application of EVT in LVO populations that fall outside the established criteria.

Large Core Strokes

The notion that EVT is futile for people with LVO and substantial volume of irreversible tissue damage (eg, large core strokes; Figure) is based on an anticipated high risk of hemorrhagic transformation and poor functional outcomes despite treatment. Recent studies have delved deeper into the role of EVT in this population. ANGEL-ASPECT (Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core, NCT04551664),³ published in 2023, investigated the safety and efficacy of medical management (MM) plus EVT vs MM alone in cases of anterior circulation LVO with a low ASPECTS (3 to 5). This trial, conducted in China with 456 participants, revealed better 90-day functional outcomes in people treated with EVT (odds ratio [OR], 1.37; 95% CI, 1.11–1.69). The occurrence of symptomatic intracranial hemorrhage (sICH) was significantly higher in the EVT group (6.1%) compared with the MM group (2.7%). Mortality rates were high but similar between the 2 treatment groups (21.7% in the EVT group and 20% in the MM group).

Another international multicenter study published in 2023, SELECT-2 (A Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke, NCT03876457),⁴ included 352 people with large core infarction (ASPECTS 3 to 5) randomly assigned to EVT or MM. The EVT group had a higher percentage of participants achieving functional independence compared with the MM group (20% vs 7%), with a generalized OR for a shift in mRS score distribution favoring EVT of 1.51 (95% CI, 1.20–1.89). Death within 90 days was similar across treatment groups (38.4% in the EVT group and 41.5% in the MM group), and sICH occurred in only 0.6% of the EVT group. The results of these 2 RCT support that people with LVO and lower ASPECTS can benefit from EVT, despite their higher likelihood of poor outcomes compared with individuals who present with a smaller infarct core.

Low NIHSS Score Strokes

Pivotal RCT on EVT primarily focused on people with stroke presenting with disabling symptoms (NIHSS score ≥6). However, nearly 10% to 20% of individuals with low presenting NIHSS scores have LVO, which is associated with a more than 10-fold likelihood of early neurologic deterioration and infarct expansion within 48 hours.⁵ Despite this, much of our understanding of EVT in cases of low NIHSS strokes is derived from small observational studies, and no RCT have been conducted to examine EVT safety and efficacy specifically in this context. A retrospective analysis of a prospective stroke registry in China evaluated the outcomes of individuals who received either MM or EVT, including both immediate and rescue EVT. In this analysis, EVT was not associated with excellent functional outcomes (mRS score 0 to 1). However, EVT selection based on perfusion imaging was an effect modifier, as EVT resulted in a higher odds of having an excellent outcome among the subgroup of people who had significant mismatch between hypoperfused and infarcted tissue.⁶

In another international prospective analysis comparing immediate EVT with MM, with MM including rescue EVT, it was observed that immediate EVT was an independent predictor of a good outcome (OR, 3.1; 95% CI, 1.4–6.9), with an absolute difference of 15%.⁷ Although there is some potential in improving functional outcomes with the use of EVT in low NIHSS strokes, the existing data primarily come from observational studies, thus requiring cautious interpretation. Two RCT—MOSTE (Minor Stroke Therapy Evaluation, NCT03796468) and ENDOLOW (Endovascular Therapy for Low NIHSS Ischemic Strokes, NCT04167527)—are enrolling participants to investigate the safety and efficacy of EVT in low NIHSS score strokes. As more research emerges, a better understanding of the outcomes of EVT in low NIHSS score strokes will be obtained.

Premorbid Disability

The potential benefits of EVT in individuals with advanced age, baseline disability, or dementia remain a topic of debate, primarily because of the underrepresentation of these populations in RCT assessing EVT efficacy and safety. For intravenous thrombolysis, a meta-analysis demonstrated that individuals with premorbid disability had a more favorable odds of returning to baseline function, with no significant differences in mortality rate or sICH compared with the untreated group.⁸ Several observational studies, including case series and registry-based studies, have shown comparable safety of EVT in people with premorbid disability and dementia compared with those without, and suggest a potential benefit in returning to a prestroke functional level of disability with EVT compared with MM alone.⁹ Therefore, although mortality rates are higher in this population, individuals with advanced age or premorbid disability are likely to benefit from EVT in the appropriate medical setting, and the decision to omit EVT treatment based solely on age or functional baseline status should be avoided.

Basilar Artery Occlusion

The mortality rate in cases of BAO can range from 83% to 96% if reperfusion is not achieved.¹⁰ Four RCT have been conducted to assess the outcomes and complications of EVT in this population. Two early trials failed to show superiority of EVT over MM; however, they were underpowered.^11,12 More recently, ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion, NCT04751708) and BAOCHE (Basilar Artery Occlusion Chinese Endovascular Trial, NCT02737189), both published in 2022,^13,14 included people with BAO within 0 to 12 hours and 6 to 24 hours of symptom onset, respectively, and showed that EVT was superior to MM in terms of good (mRS score 0 to 3) or excellent (mRS score 0 to 2) outcomes at 90 days. One important caveat of the aforementioned trials is that individuals with high infarct burden as determined by a posterior circulation ASPECTS <6 were excluded. A meta-analysis of these 4 RCT, with a total sample size of 988 participants, revealed that EVT is associated with 2-fold higher odds of favorable outcomes compared with MM. The overall rate of sICH was higher in the EVT group (5.4%) compared with the MM group (0.8%). However, the EVT group had lower odds of death (OR, 0.64; 95% CI, 0.42–0.99).¹⁵ Therefore, updated evidence supports the use of emergent EVT for people with BAO strokes.

Conclusion

Despite the established effectiveness of EVT in selected people with LVO strokes, certain populations have been excluded from the current guideline recommendations because of their limited representation in landmark RCT. Individuals with large core stroke or baseline disability typically were excluded from these trials, as aggressive interventions were believed to be futile in improving outcomes. However, emerging RCT have demonstrated an increased likelihood of favorable outcomes in people with large core strokes when treated with EVT, despite the higher probability of severe disability and death within this population. Observational data suggest that EVT is effective in improving the likelihood of returning to baseline status in people with premorbid disability. Therefore, EVT should not be omitted based solely on baseline functional status or age. The efficacy of EVT for individuals with low NIHSS scores remains a subject of controversy. Recent well-designed trials have provided evidence-based management for BAO strokes. As new data continue to emerge regarding the safety and efficacy of EVT, the treatment paradigm is evolving. People with LVO who do not fit the traditional criteria may benefit from EVT. Therefore, it is important to consider individualized treatment approaches and explore the expanding possibilities for EVT in diverse populations.