Despite major advances in acute reperfusion therapies, stroke continues to leave approximately one in four survivors with significant disability (1,2). Endovascular thrombectomy (EVT) has transformed the management of ischemic stroke, significantly reducing both disability and mortality (3). It is estimated that 25 to 46% of acute ischemic strokes present with large vessel occlusions amenable to EVT (4), however, its use remains limited to select centres and patients meeting specific eligibility criteria. Current criteria for EVT typically requires the presence of disabling neurological deficits, often defined by a National Institutes of Health Stroke Scale (NIHSS) score of ≥5, along with neuroimaging evidence of a large vessel occlusion in either the internal carotid artery, middle cerebral artery, or basilar artery, and consultation with an interventional specialist. The presence of a large ischemic core has often been considered a contraindication to EVT, and is commonly assessed using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) where salvageable brain tissue confers a score of ≥6 (5). More recently, randomized controlled trials (RCTs) have demonstrated that EVT for ischemic stroke with larger core volume, with an ASEPCTS 3 to 5, leads to better 1-year outcomes compared to medical management (6-9). One additional RCT, the TENSION trial (10), also observed better 90-day functional outcomes in patients with a larger infarct core undergoing EVT. However, not all findings have been similar; particularly, the TESLA trial did not show any significant differences in those receiving EVT vs. medical management at 90 days post-stroke (11).
In a recent issue of International Journal of Stroke, Winkelmeier et al. (12) provide a timely comparison of how well the results of RCTs apply to real-world practice when treating patients with large ischemic stroke with EVT. In this study, a total of 198 participants from the TENSION RCT (10) and German Stroke Registry meeting the TENSION trial eligibility criteria were identified and underwent EVT. Before propensity score matching, there were differences between the two groups. For example, median baseline NIHSS was lower in the German Registry (NIHSS 17 vs. 19 in the TENSION cohort, P=0.001), with more individuals presenting with a baseline ASPECTS of 5 (52.2% vs. 34.7%, P=0.007), and patients presented faster to hospital with less time between symptom onset or last seen well time and 1) hospital arrival/randomization and 2) groin puncture for EVT. After propensity score matching, the median ASPECTS was 4 and pre-treatment NIHSS was 18 in both groups. The primary outcome was the score on the modified Rankin scale (mRS) at 90 days post-stroke, and they found no significant shift in the distribution of 90-day mRS scores toward better functional independence among patients in the RCT vs. those treated in routine clinical practice [adjusted odds ratio (aOR) 1.19, 95% confidence interval (CI): 0.70–2.02; P=0.52]. Moreover, treatment within the TENSION trial was not associated with a higher odds of achieving independent ambulation at 90 days post-stroke compared to those treated in the German Stroke Registry (aOR 1.19, 95% CI: 0.61–2.32; P=0.62). The rates of symptomatic intracranial hemorrhage and mortality were also comparable. Overall, the clinical outcomes were broadly consistent with those observed in the TENSION RCT when the patients from the German Registry met the TENSION trial inclusion criteria. These findings are encouraging and mirror those of others suggesting that EVT benefits patients with an established, substantial burden of infarction (6-9,11).
Whether the findings of these RCTs translates into clinical practice, however, remains uncertain. An important question remains: how consistently is the randomized trial framework for patient selection being followed or consciously used as a guideline in everyday practice when determining patient eligibility for EVT in those with large ischemic stroke? In the comparison by Winkelmeier et al., only around half of the patients in the German Stroke Registry met the TENSION criteria (n=184 before and n=99 after propensity matching). The use of propensity score matching may have introduced potential selection bias, and the subsequent small sample size adds to the study’s methodological limitations. Furthermore, patients treated in routine clinical practice are often more heterogeneous compared to those meeting the strict inclusion criteria of RCTs, and this heterogeneity is lost with the present methodology. For example, baseline characteristics before propensity score matching in the present study by Winkelmeier et al. identifies a higher ASPECTS and lower median NIHSS in the registry group, which may suggest less extensive infarction than individuals in the TENSION RCT, and may impact more favorable clinical outcomes. Moreover, Winkelmeier et al.’s Fig. 1 demonstrates that a very large proportion of patients were excluded before matching, with a substantial number missing data. Therefore, it remains unclear whether the matched, curated subgroup from the registry truly represents everyday decision-making around EVT in this patient population.
The study also has other limitations that warrant consideration. First, the study was completed in a single, highly resourceful country, which may limit generalizability to healthcare systems with different resources. Additionally, sensitivity or subgroup analyses were not completed with demographic features, such as by sex, which could offer further insights into which patients are likely to derive the most benefit from EVT despite large infarct core. Second, variability in imaging protocols and definitions of infarct core between the TENSION trial and registry practice may limit comparison. While both neuroimaging modalities, computed tomography (CT) and magnetic resonance imaging (MRI) are only modestly comparable in estimating infarct core volume and using both within the same study to define infarct core merits caution. Diffusion-weighted MRI has been shown to have greater sensitivity for detecting early ischemic change (13), whereas CT-based ASPECTS and CT-perfusion are more susceptible to varying imaging quality and inter-rater variability. These limitations of CT-based protocols may lead to the inconsistent interpretation of infarct core volume and subsequently, the misclassification of patients, impacting the overall interpretation of results. Interestingly, the mean infarct volume was lower in the EVT group than in individuals receiving standard medical care at 24 hours in the TENSION trial (205.8±139.1 vs. 227.7±107.2 mL in the medical care group), raising the question of how large these “large core” infarcts really were in the EVT group (10). The observed mean infarct volume in the patients included in the current study by Winkelmeier et al. from the TENSION cohort and German Registry is unknown. Finally, there was a greater number of participants in the TENSION cohort that received intravenous thrombolysis in addition to EVT compared to the German Registry (44.4% vs. 34.3%) despite the presence of large infarct core, which would warrant further discussion and possible sensitivity analysis to determine whether this impacted clinical and procedural outcomes (i.e., reperfusion score), given the risks of potential associated reperfusion injury and hemorrhagic transformation when administering thrombolysis to patients with extensive baseline established ischemic change.
Moving forward, there are important future directions to consider. Despite the emerging evidence, clinicians are often hesitant to offer EVT to patients with large infarct cores due to concerns of procedural complications and an increased risk of reperfusion injury, which may offset potential functional benefits. More trials are needed, specifically those with broader inclusion criteria and that reflect the heterogeneity in real-world care, to bridge the gap between “efficacy” observed in ideal, highly controlled conditions (i.e., clinical trials) and “effectiveness” in everyday clinical practice. Additionally, subgroup analyses focused on advanced age, sex, and significant medical comorbidities will help to determine which subgroups may have the greatest benefit from EVT despite a large burden of infarct. Finally, the standardization of imaging criteria, particularly for defining large core infarcts, along with standardization of imaging modalities, is crucial to ensure consistent patient selection, as previous studies have been limited in the heterogeneity of their paradigms using qualitative measures such as CT and ASPECTS, or quantitative measures including perfusion-based CT or MRI, which further limits their generalizability.
In summary, the findings of Winkelmeier et al. suggests that extending EVT to patients with large ischemic infarcts may mirror the findings of RCTs. While clinical outcomes from the TENSION trial and German Stroke Registry cohorts were comparable, the true effectiveness of EVT in this patient population outside of the RCT setting remains uncertain.
Acknowledgments
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Cite this article as: Kuczynski AM, Barber PA. Endovascular thrombectomy for acute ischemic stroke with large infarct core: translating results from a randomized trial into clinical practice. Ann Transl Med 2026;14(5):76. doi: 10.21037/atm-2026-0126
