Endovascular Treatment in Large-Core Stroke Patients With Prestroke Disability Underrepresented in Clinical Trials

Article information

J Stroke. 2025;27(3):418-421

Publication date (electronic) : 2025 September 29

doi : https://doi.org/10.5853/jos.2025.00668

Johannes Wischmann¹, Hanna Zimmermann², Thomas Liebig², Lars Kellert^,1, for the German Stroke Registry–Endovascular Treatment (GSR-ET) Investigators^*

¹Department of Neurology, Ludwig-Maximilians-University (LMU) Hospital, LMU Munich, Munich, Germany

²Institute of Neuroradiology, Ludwig-Maximilians-University (LMU) Hospital, LMU Munich, Munich, Germany

Correspondence: Lars Kellert Department of Neurology, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany Tel: +49-89-4400-76676 E-mail: lars.kellert@med.uni-muenchen.de

*The member of the committee is provided in Appendix.

Received 2025 February 7; Revised 2025 April 24; Accepted 2025 June 13.

Dear Sir:

Recent randomized controlled trials have demonstrated that endovascular treatment (ET) is effective and safe even in large-core stroke patients with an Alberta Stroke Program Early CT Score (ASPECTS) of 0–5 [1-6]. However, patients with prestroke disability were underrepresented in these trials, despite approximately up to 30% of acute stroke patients encountered in clinical practice having a premorbid modified Rankin Scale (pmRS) score of >2 [7]. Given the available evidence, it is important to evaluate whether large-core stroke patients with prestroke disability could benefit from ET, particularly as low-ASPECTS strokes have poorer prognoses even in patients without prior disabilities. To address this gap, we compared outcome and safety profiles of low-ASPECTS patients with and without prestroke disability in a real-world clinical setting. Additionally, we aimed to identify predictors of clinical and radiological outcomes in patients with prestroke disability (i.e., pmRS 3–5). We utilized data from the German Stroke Registry–Endovascular Treatment (GSR-ET), a prospective multicenter registry (25 participating centers) of stroke patients undergoing ET (NCT03356392) [8]. Patients registered between June 2015 and December 2023 (n=18,069) were reviewed. The study was centrally approved by the Ethics Committee of LMU Munich (protocol: 689–15), serving as the leading ethics committee. Additional approval was obtained from local ethics committees, as required by local regulations. Data collection for the registry was approved under a waiver of informed consent by the institutional review boards at each participating center.

A total of 605 patients (mean age [±SD] 73.4±13.7 years; 329 [54.4%] female) who underwent ET for internal carotid artery, M1, or M2 occlusions with an ASPECTS of ≤5, presenting within 24 hours of symptom onset, were included. Among them, 92 patients (15.2%) had a pmRS of 3–5, while 513 (84.8%) had a pmRS ≤2. Details of the patient selection are presented in Supplementary Figure 1 and Supplementary Methods. Comparisons between eligible patients and those excluded due to missing ASPECTS and/or 90-day modified Rankin Scale (mRS) scores are presented in Supplementary Table 1. The primary outcome was the mRS shift at 90 days. Secondary outcomes included return to baseline mRS, mortality, National Institutes of Health Stroke Scale (NIHSS) at 24 hours, symptomatic intracranial hemorrhage (sICH), procedure-related complications, and successful recanalization (modified Thrombolysis In Cerebral Infarction [mTICI] score ≥2b). Associations between prestroke disability and outcomes were assessed using multivariate regression models. Predictors for effective ET (defined as achieving an mTICI score of 2b–3 and either a return to pmRS at 90 days or a worsening of no more than 1 point on the mRS at 90 days compared to the pmRS), mortality, and successful recanalization were identified, utilizing a backward stepwise regression approach. Effect estimates were adjusted for known covariates and differences between both groups in univariate analyses (Supplementary Tables 2-4).

At 90 days, prestroke disability was associated with a shift towards worse functional outcomes in ASPECTS ≤5 patients (adjusted odds ratio [aOR] 2.43; 95% confidence interval [CI] 1.33–4.28; P<0.001) (Table 1 and Figure 1A). Mortality was higher in pmRS 3–5 compared to pmRS ≤2 patients (70.7% vs. 43.3%; aOR 2.01; 95% CI 1.17–3.54; P=0.012). All other secondary outcomes, including NIHSS at 24 hours (20 vs. 17), sICH (7.6% vs. 6.6%), successful recanalization (77.2% vs. 82.1%), and procedure-related complications (16.3% vs. 10.7%), were comparable between both groups. Details of the univariate analysis are presented in Supplementary Table 5. In the subgroup of patients with prestroke disability, the average rate of return to baseline mRS at 90 days was 14.0%, with the highest rate observed in patients with a pmRS of 5 (20.0%) and the lowest in those with pmRS 3 (10.8%). Mortality was lowest among patients with pmRS 3 (44.0%) and highest among those with pmRS 5 (80%) (Figure 1B). Clinical and radiological outcomes are summarized in Table 1. In pmRS 3–5 and ASPECTS ≤5 patients, effective ET was independently associated with younger age (aOR 0.96; 95% CI 0.91–1.00; P=0.049) and higher ASPECTS (aOR 1.96; 95% CI 1.01–3.81; P=0.048) (Figure 2A). Conversely, higher age (aOR 1.07; 95% CI 1.02–1.13; P=0.004) and lower ASPECTS (aOR 0.57; 95% CI 0.33–0.98; P=0.042) independently predicted mortality in those patients (Figure 2B). Fewer recanalization attempts (aOR 0.66; 95% CI 0.50–0.89; P=0.006) and lower NIHSS scores (aOR 0.84; 95% CI 0.75–0.95; P=0.004) were associated with successful recanalization (Figure 2C).

Table 1.

Clinical and radiological outcomes

Figure 1.

mRS shift analysis and return to baseline mRS and mortality rates. (A) Distribution of scores on the mRS at 90 days in pmRS 0–2 compared to pmRS 3–5 patients. (B) Return to baseline mRS and 90-day mortality rates stratified by pmRS in ASPECTS ≤5 patients. ASPECTS, Alberta Stroke Program Early CT Score; pmRS, premorbid modified Rankin Scale.

Figure 2.

Predictors associated with (A) effective ET, (B) 90-day mortality, and (C) mTICI ≥2b in ASPECTS ≤5 patients with pmRS 3–5. Effective ET was defined as achieving an mTICI score of 2b-3 and either a return to pmRS at 90 days or a worsening of no more than 1 point on the mRS at 90 days compared to the pmRS. Only independent variables with P<0.05 are shown in each respective model. ET, endovascular treatment; aOR, adjusted odds ratio; ASPECTS, Alberta Stroke Program Early CT Score; NIHSS, National Institutes of Health Stroke Scale.

Similar to ET outcomes in higher ASPECTS strokes, prestroke disability was associated with worse clinical outcomes in this study. On average, seven out of ten patients died, particularly those who were older, had more severe strokes, and had lower ASPECTS scores. Return to baseline mRS was achieved in only one out of seven patients, which is consistent with expectations given the large-core infarcts in our cohort. This finding aligns with the MR CLEAN Registry, which reported a 27% return to baseline mRS in prestroke-dependent patients, albeit with a higher median ASPECTS of 9 [9]. ET showed effectiveness primarily in younger patients with higher ASPECTS, consistent with previous studies investigating ET in patients with ASPECTS scores of 6–10 [10]. Importantly, prestroke disability did not appear to impact the safety of ET in large-core infarcts. We observed comparable sICH rates of 6%–8%, consistent with those reported in recent randomized controlled trials, and no differences in procedure-related complications [1-6]. Limitations of this study include a potential selection bias in analyzing low-ASPECTS patients with prestroke disability, as clinicians are likely aware of the generally poor prognosis and may only indicate ET in selected patients with a meaningful chance of clinical benefit. This is reflected in the overall limited sample size and specifically in the underrepresentation of patients with pmRS 5 in this study. As a result, actual mortality rates may be higher, and functional outcomes could be worse than reported here. However, the distribution of mRS scores among patients with pmRS 0–2 closely aligns with that observed in pivotal large-core infarct trials, suggesting that the data are likely representative of premorbid patients, particularly with regard to the high mortality rates. Furthermore, the proportion of patients shipped to the ET center was nearly 30% higher among those excluded from the study due to missing data, compared to eligible patients, which may have influenced our findings. Additionally, patients with very low ASPECTS (0–2) are underrepresented in our analysis. In fact, nearly 60% of patients with prestroke disability had an ASPECTS of 5, and no patients with an ASPECTS of 0 were included.

In conclusion, large-core stroke patients with prestroke disability face exceptionally poor prognoses, with high mortality rates. However, a return to baseline mRS is achievable in a small proportion of selected cases, particularly in younger patients with higher ASPECTS scores. Importantly, prestroke disability does not appear to affect the safety of ET in these patients. These findings may support clinicians in shared decision-making with large-stroke patients who have prestroke disability and their proxies.