Futile recanalization after mechanical thrombectomy in patients with acute ischemic stroke and large ischemic core

Yuichiro Tsuji; Kohei Tsujino; Ryokichi Yagi; Ryo Hiramatsu; Yoshitaka Yamada; Masahiko Wanibuchi

doi:10.7461/jcen.2025.E2025.09.001

J Cerebrovasc Endovasc Neurosurg > Epub ahead of print

Tsuji, Tsujino, Yagi, Hiramatsu, Yamada, and Wanibuchi: Futile recanalization after mechanical thrombectomy in patients with acute ischemic stroke and large ischemic core

Clinical Article

Journal of Cerebrovascular and Endovascular Neurosurgery 2025;jcen.2025.E2025.09.001.

Published online: December 31, 2025

DOI: https://doi.org/10.7461/jcen.2025.E2025.09.001

Futile recanalization after mechanical thrombectomy in patients with acute ischemic stroke and large ischemic core

Yuichiro Tsuji¹

, Kohei Tsujino², Ryokichi Yagi¹, Ryo Hiramatsu¹, Yoshitaka Yamada³, Masahiko Wanibuchi¹

¹Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka, Japan

²Department of Neurosurgery, Shimizu Hospital, Kyoto, Japan

³Department of Neurosurgery, Nishinomiya Kyoritsu Neurosurgery Hospital, Nishinomiya, Hyogo, Japan

Correspondence to Yuichiro Tsuji Department of Neurosurgery, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi Takatsuki-city, Osaka, Japan Tel +81726831221 Fax +81726813723 E-mail yuuichirou.tsuji@ompu.ac.jp

Received September 8, 2025 Revised December 8, 2025 Accepted December 8, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Multiple randomized controlled trials have demonstrated the efficacy of mechanical thrombectomy (MT) for acute ischemic stroke with a large ischemic core caused by large-vessel occlusion. Despite successful recanalization, more than half of the patients do not achieve a favorable prognosis, a phenomenon referred to as futile recanalization (FR). We aimed to identify the risk factors for, and incidence of, FR in patients with large ischemic cores.

Methods

Eighty-four patients with a large ischemic core who underwent MT between January 2015 and December 2024 at three hospitals were retrospectively reviewed. Patients were divided into two groups—FR and no-FR—according to functional independence at 90 days (modified Rankin Scale (mRS) score ≥4). Factors influencing FR were identified using multivariate logistic regression and receiver operating characteristic curve analyses.

Results

Eighty-four patients fulfilled the inclusion criteria, and FR was observed in 57 patients (67.9%). Multivariable regression analysis revealed that older age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.01-1.18; P=0.011), concomitant diabetes (OR, 11.2; 95% CI, 1.13-111.1; P=0.012), diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (OR, 0.32; 95% CI, 0.11-0.79; P=0.012), and an increased number of passes (OR, 1.91; 95% CI, 1.00-4.16; P=0.046) were independently associated with FR after MT.

Conclusions

Older age, concomitant diabetes, diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score, and an increased number of passes are independently associated with FR after MT in patients with a large ischemic core.

Keywords: Ischemic stroke, Mechanical thrombectomy, Futile recanalization, Large ischemic core, Large vessel occlusion

INTRODUCTION

Multiple randomized controlled trials have shown that, compared to medical therapy, mechanical thrombectomy (MT) for acute ischemic stroke with a large ischemic core due to large-vessel occlusion (LVO) improves functional prognosis [2,4,13,16,24,25]. However, the rate of favorable outcomes remains low at only 20-30%.

In addition, despite successful recanalization, approximately half of patients do not achieve a favorable prognosis, a condition referred to as “futile recanalization” (FR) [20]. Several studies have examined FR and reported associated factors [3,14,27]. However, patients with large ischemic changes were excluded from these studies, and the incidence of FR and related factors when MT is performed in such patients remains unclear. It is clinically important to investigate predictors of FR, particularly in patients with large ischemic changes, as they are expected to have a higher likelihood of FR. In this study, we examined the risk factors for, and incidence of, FR after MT in patients with large ischemic cores.

MATERIALS AND METHODS

Study participants

In this study, we retrospectively analyzed consecutive patients who experienced anterior circulation LVO stroke and underwent MT at three hospitals between January 2015 and December 2024. The inclusion criteria were as follows: treatment initiated within 24 h after symptom onset; confirmed occlusion of the internal carotid artery or the M1 segment of the middle cerebral artery; National Institutes of Health Stroke Scale (NIHSS) score ≥6; diffusion-weighted imaging (DWI)-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of three to five; successful recanalization (modified thrombolysis in cerebral infarction score of 2b or 3); and pre-stroke modified Rankin Scale score of zero to two. This study did not perform perfusion studies using computed tomography (CT) or magnetic resonance imaging (MRI) images. Furthermore, the present study excluded cases of tandem occlusion and medium-vessel occlusion. The Institutional Review Board (IRB) approved this study, which was conducted according to the ethical standards laid down by the Declaration of Helsinki (IRB no. 2024-099), and informed consent was obtained from all patients.

Data collection

The following information was collected: age, sex, medical history (hypertension, atrial fibrillation, diabetes mellitus [DM], and hyperlipidemia), clinical data (baseline blood pressure, Trial of ORG 10172 in Acute Stroke Treatment classification, NIHSS score, and ASPECTS at admission), and laboratory data within 24 hours. Surgery-related data, assessed and recorded by the surgical team, included the time from symptom onset to puncture, time from puncture to revascularization, site of the occluded vessel, and revascularization grade. A history of DM or an HbA1c ≥6.5% was considered diagnostic for DM.

Definition of FR

FR was defined as a poor clinical outcome modified Rankin Scale (mRS) score, 4-6) at 3 months after stroke despite successful recanalization (modified thrombolysis in cerebral infarction score, 2b-3), whereas the non-FR group experienced a good clinical outcome (mRS score, 0-3) at 3 months. Patients were divided into two groups: FR and non-FR.

Statistical analysis

Continuous variables were expressed as median (interquartile range), whereas categorical variables were expressed as frequency (percentage). Student’s t-test and chi-squared test were used to compare the FR and non-FR groups. Factors that were statistically significant in the univariate analysis were included in the multivariate regression analysis. Receiver operating characteristic curve analysis was used to identify predictive factors. Differences were considered statistically significant at P<0.05. Statistical analyses were performed using JMP software (version 17.0; SAS Institute, Inc., Cary, NC, USA).

RESULTS

During the study period, 103 patients with large ischemic cores underwent MT for acute stroke. Nineteen patients were excluded for the following reasons: unsuccessful recanalization (n=9) or a pre-mRS score>3 before onset (n=10). Eighty-four patients fulfilled the inclusion criteria, of whom 57 (67.9%) were assigned to the FR group and 27 (32.1%) to the non-FR group (Fig. 1).

Compared with patients in the non-FR group, those in the FR group were significantly older (median 80 vs. 72 years, P=0.007), had significantly higher NIHSS scores (median 20 vs. 16, P=0.002), had significantly lower DWI-ASPECTS scores (median 4 vs. 5, P=0.046), and had a significantly higher number of passes (median 2 vs. 1, P=0.037) (Tables 1 and 2).

Multivariate analysis revealed that older age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.01-1.18; P=0.011), concomitant diabetes (OR, 11.2; 95% CI, 1.13-111.1; P=0.012), DWI-ASPECTS (OR, 0.32; 95% CI, 0.11-0.79; P=0.012), and number of passes (OR, 1.91; 95% CI, 1.00-4.16; P=0.046) were determined to be independently associated with the occurrence of FR after MT in patients with a large ischemic core (Table 3).

Using the receiver operating characteristic curves from logistic regression analysis, the predictive accuracies of age, diabetes, dominant side, NIHSS score, DWI-ASPECTS score, number of passes, and symptomatic intracerebral hemorrhage (sICH) were identified. This model exhibited the best performance with an area under the curve of 0.86 (P<0.05).

DISCUSSION

MT has been shown to be more effective than medical therapy for acute ischemic stroke with a large ischemic core caused by LVO [2,4,13,16,24,25]. Conversely, previous studies have reported that the proportion of FR ranged from 49.7% to 66.6% in LVO of the anterior circulation with a large ischemic core [6,22], and the incidence of FR was also very high (approximately 68%) in the present study. Although meta-analyses of FR-related factors were performed [3,14], patients with low DWI-ASPECTS scores were excluded. In this study, older age, lower DWI-ASPECTS, concomitant diabetes, and an increased number of passes were independently associated with the occurrence of FR.

Our results demonstrated that the OR for FR was 1.08 per year of advancing age, with a cutoff of 72 years. Previous meta-analyses have confirmed that age is an important factor associated with FR, which is consistent with this result [3,14,15]. Kim et al. showed that older age is a risk factor for FR in cases with a large ischemic core [6]. Yi et al. reported that, among patients with a large ischemic core, those older than 68 years had a threefold higher risk of FR [22]. If similar results are reported in the future, the indications for MT may be reconsidered in older patients with large ischemic cores. The possible mechanisms include cerebrovascular self-regulation and collateral blood flow disorders caused by aging [10]. In addition, increased comorbidities, increased incidence of complications, and decreased rehabilitation efficiency are more likely to occur in older patients than in younger patients [8,15].

Results of this study revealed that DWI-ASPECTS score ≤3 was associated with FR. To the best of our knowledge, this is the first study to show an association between the DWI-ASPECTS and FR in LVO with a large ischemic core. In the post-hoc analysis of RESECU-Japan Limit, the efficacy of endovascular treatment was not demonstrated in the group with DWI-ASPECTS ≤3 compared to medical treatment [18]. In patients with large ischemic cores, a DWI-ASPECTS score of ≤3 may be specified as a cutoff point related to treatment outcomes in the future. Conversely, Yoshimoto et al. suggested that the threshold for ischemic core volume associated with poor prognosis is ≥71 mL and that a DWI-ASPECTS score of four points may be a cutoff point for treatment [23]. In the present study, we did not evaluate the volume of the ischemic core using perfusion imaging. Because we performed evaluations based on DWI-ASPECTS, it is important to note that there is a possibility of overestimating acute ischemic lesions in the perforating arterial region of the middle cerebral artery (MCA) compared with observations using computed tomography.

Diabetic complications were also associated with FR. Hyperglycemia in patients with acute ischemic stroke leads to mechanisms, such as altered blood-brain barrier permeability [12], increased intracellular acidosis due to the accumulation of lactic acid [11], and increased oxidative stress response [19]. Consequently, inflammatory responses are accelerated, leading to impaired vascular endothelial function. It also causes complications, such as reperfusion injury and hemorrhagic infarction [21]. Yi et al. also reported that diabetes was associated with FR after MT in patients with a large ischemic core [22]. Furthermore, elevated serum glucose levels on admission are associated with poor prognosis in patients with a large ischemic core [7]. However, in the present study, there was no correlation between blood glucose levels at admission and FR.

This study showed that an increased number of passes was associated with FR. The association between the number of passes and FR has been reported previously [1,9], and our earlier study showed similar results [17]. The first-pass effect has been shown to be associated with good clinical outcomes 90 days after MT [5]. The median number of passes in the non-FR group was one, suggesting a higher first-pass effect in that group. In general, an increased number of passes correlates with P2R; however, in this study, no correlation was found between the number of passes and P2R or O2R over time. In addition, an increased number of passes has been associated with hemorrhagic infarction [26]. In this study, the higher percentage of sICH in the FR group suggests an association with the number of passes.

To confirm predictive factors, this research must be further developed, which requires randomized controlled trials. However, identifying these factors might lead to the following medical ethical issue: The problem is that MT would not be presented as a treatment option for patients with low therapeutic efficacy. As the aging population progresses, the issue of patient selection could become more significant.

The present study had several limitations. The first was its three-center, retrospective, observational design. As such, prospective and multicenter studies are required. Second, the small sample size may have limited statistical power and may have introduced selection bias and errors. Third, this study did not evaluate ischemic core volume using perfusion images, assessing only DWI-ASCPTES. Ischemic core volume from perfusion images could potentially be a contributing factor to FR, but this data was lacking in this study.

CONCLUSIONS

Our results demonstrate that the incidence of FR was high, affecting nearly 70% of patients with large ischemic cores. Older age, concomitant diabetes, lower DWI-ASPECTS score, and an increased number of passes were independent predictors of FR.

NOTES

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Fig. 1.

Flow diagram of this study. FR, futile recanalization; mRS, modified Rankin Scale; MT, mechanical thrombectomy

Table 1.

Comparisons of characteristics between futile recanalization (FR) and non-FR groups

Variables	FR (n=57)	Non-FR (n=27)	P-value
Age (years), median (IQR)	80 (74-87)	72 (67-80)	0.007
Female, n (%)	28 (49.1)	13 (48.1)	0.93
Risk factors, n (%)
Hypertension	34 (59.6)	16 (59.2)	0.97
Diabetes mellitus	12 (21.0)	1 (3.7)	0.052
Dyslipidemia	13 (22.8)	4 (14.8)	0.56
Arterial fibrillation	43 (75.4)	20 (74.0)	0.89
TOAST classification, n (%)
Large arterial atherosclerosis	3 (5.2)	1 (3.7)	0.75
Cardioembolism	47 (82.4)	21 (77.7)	0.76
Undetermined etiology	6 (10.5)	5 (18.5)	0.32
Occlusion location, n (%)
ICA	30 (52.6)	16 (59.2)	0.64
MCA (M1)	27 (47.3)	11 (40.7)	0.64
Left side	30 (52.6)	8 (29.6)	0.061
Laboratory data and clinical findings
SBP, mmHg	147 (130-166)	148 (144-169)	0.25
DBP, mmHg	90 (76-104)	91 (81-107)	0.22
Baseline blood glucose, mmol/l	6.8 (5.8-9.9)	6.7 (6.2-8.0)	0.19
NIHSS score	20 (17-25)	16 (13-21)	0.002
DWI-ASPECTS score	4 (3-5)	5 (4-5)	0.046

FR, futile recanalization; TOAST, Trial of Organ Acute Stroke Treatment; ICA, internal cerebral artery; MCA, middle cerebral artery; SBP, systolic blood pressure; DBP, diastolic blood pressure; NIHSS, National Institutes of Health Stroke Scale; DWI-ASPECTS, Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores

Table 2.

Comparison of endovascular treatment outcomes between futile recanalization (FR) and non-FR groups

Variables	FR (n=57)	Non-FR (n=27)	P-value
Intravenous tPA, n (%)	9 (15.7)	8 (29.6)	0.15
Type of device used for MT, n (%)
Aspiration catheter	15 (26.3)	10 (37.0)	0.32
Stent retriever	13 (22.8)	6 (22.2)	0.95
Aspiration catheter plus stent retriever	29 (50.8)	11 (40.7)	0.48
Number of passes (IQR)	2 (1-3)	1 (1-2)	0.043
First pass effect	21 (36.8%)	15 (55.5%)	0.15
Time parameters, min, median (IQR)
From onset to puncture	209 (143-411)	240 (111-358)	0.38
From puncture to reperfusion	44 (30-66)	33 (23-56)	0.13
From onset to reperfusion	266 (196-438)	267 (153-376)	0.29
Symptomatic ICH	12 (21.0%)	1 (3.7%)	0.052

FR, futile recanalization; tPA, tissue-type plasminogen activator; MT, mechanical thrombectomy; ICH, internal cerebral hemorrhage

Table 3.

Multivariable regression analysis for futile recanalization (FR)

Variables	Adjusted OR (95% CI)	P-value
Age	1.09 (1.02-1.18)	0.013
Diabetes mellitus	9.90 (1.03-94.9)	0.046
DWI-ASPECTS score	0.10 (0.01-0.62)	0.019
Left side	2.21 (0.57-8.48)	0.24
NIHSS	1.10 (0.97-1.28)	0.13
Number of passes	1.96 (1.03-4.28)	0.036
Symptomatic ICH	2.31 (0.18-28.9)	0.51

DWI-ASPECTS, Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores; NIHSS, National Institutes of Health Stroke Scale; ICH, internal cerebral hemorrhage

REFERENCES

1. Baek JH, Kim BM, Heo JH, Nam HS, Kim YD, Park H, et al. Number of stent retriever passes associated with futile recanalization in acute stroke. Stroke. 2018 Sep;49(9):2088-95.

2. Chen H, Lee JS, Michel P, Yan B, Chaturvedi S. Endovascular stroke thrombectomy for patients with large ischemic core: A review. JAMA Neurol. 2024 Oct;81(10):1085-93.

3. Deng G, Xiao J, Yu H, Chen M, Shang K, Qin C, et al. Predictors of futile recanalization after endovascular treatment in acute ischemic stroke: A meta-analysis. J Neurointerv Surg. 2022 Sep;14(9):881-5.

4. Huo X, Ma G, Tong X, Zhang X, Pan Y, Nguyen TN, et al. Trial of endovascular therapy for acute ischemic stroke with large infarct. N Engl J Med. 2023 Apr;388(14):1272-83.

5. Jadhav AP, Desai SM, Zaidat OO, Nogueira RG, Jovin TG, Haussen DC, et al. First pass effect with neurothrombectomy for acute ischemic stroke: Analysis of the systematic evaluation of patients treated with stroke devices for acute ischemic stroke registry. Stroke. 2022 Feb;53(2):e30-e2.

6. Kim H, Kim JT, Choi KH, Yoon W, Beak BH, Kim SK, et al. Futile recanalization after endovascular treatment in acute ischemic stroke with large ischemic core. BMC Neurol. 2024 Oct;24(1):395.

7. Li Y, Tao H, Liu H, Fan X, Zhong MY, Huang J, et al. Endovascular therapy and medical management of large-core infarcts: Prognostic determinants in a retrospective cohort. Front Neuro. 2025 Jun;16:1595054.

8. Marini C, Baldassarre M, Russo T, Santis FD, Sacco S, Ciancarelli I, et al. Burden of first-ever ischemic stroke in the oldest old: Evidence from a population-based study. Neurology. 2004 Jan;62(1):77-81.

9. Ni H, Liu X, Hang Y, Jia Z, Cao Y, Shi H, et al. Predictors of futile recanalization in patients with acute ischemic stroke undergoing mechanical thrombectomy in late time windows. Front Neurol. 2022 Sep;13:958236.

10. Reinhard M, Rutsch S, Lambeck J, Wihler C, Czosnyka M, Weiller C, et al. Dynamic cerebral autoregulation associates with infarct size and outcome after ischemic stroke. Acta Neurol Scand. 2012 Mar;125(3):156-62.

11. Robbins NM, Swanson RA. Opposing effects of glucose on stroke and reperfusion injury: Acidosis, oxidative stress, and energy metabolism. Stroke. 2014 Jun;45(6):1881-6.

12. Rom S, Zuluaga-Ramirez V, Gajghate S, Seliga A, Winfield M, Heldt NA, et al. Hyperglycemia-driven neuroinflammation compromises BBB leading to memory loss in both diabetes mellitus (DM) type 1 and type 2 mouse models. Mol Neurobiol. 2019 Mar;56(3):1883-96.

13. Sarraj A, Hassan AE, Abraham MG, Ortega-Gutierrez S, Kasner SE, Hussain MS, et al. Trial of endovascular thrombectomy for large ischemic strokes. N Engl J Med. 2023 Apr;388(14):1259-71.

14. Shahid AH, Abbasi M, Autro Larco JL, Madhami SI, Liu Y, Brinjikji W, et al. Risk factors of futile recanalization following endovascular treatment in patients with large-vessel occlusion: Systematic review and meta-analysis. Stroke Vasc Interv Neurol. 2022 Nov;2(6):e000257.

15. Singer OC, Haring HP, Trenkler J, Nolte CH, Bohner G, Reich A, et al. Age dependency of successful recanalization in anterior circulation stroke: The ENDOSTROKE study. Cerebrovasc Dis. 2013;36(5-6):437-45.

16. Thomalla G, Fiehler J, Subtil F, Bonekamp S, Aamodt AH, Fuentes B, et al. Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomized trial. Lancet Neurol. 2024 Sep;23(9):883-92.

17. Tsuji Y, Kashiwagi H, Fukumra M, Futamura G, Yagi R, Hiramatsu R, et al. Stress hyperglycemia could influence futile recanalization in patients who undergo mechanical thrombectomy for stroke caused large vessel occlusion. World Neurosurg. 2025 Mar;195:123697.

18. Uchida K, Shindo S, Yoshimura S, Toyoda K, Sakai N, Yamagami H, et al. Association between alberta stroke program early computed tomography score and efficacy and safety outcomes with endovascular therapy in patients with stroke from large-vessel occlusion. JAMA Neurol. 2022 Dec;79(12):1260-66.

19. Won SJ, Tang XN, Suh SW, Yenari MA, Swanson RA. Hyperglycemia promotes tissue plasminogen activator-induced hemorrhage by increasing superoxide production. Ann Neurol. 2011 Oct;70(4):583-90.

20. Xu H, Jia B, Huo X, Mo D, Ma N, Gao F, et al. Predictors of futile recanalization after endovascular treatment in patients with acute ischemic stroke in a multicenter registry study. J Stroke Cerebrovasc Dis. 2020 Oct;29(10):105067.

21. Yao M, Hao Y, Wang T, Xie M, Li H, Feng J, et al. A review of stress-induced hyperglycaemia in the context of acute ischaemic stroke: Definition, underlying mechanisms, and the status of insulin therapy. Front Neurol. 2023 Mar;14:1149671.

22. Yi T, Huo X, Lin X, Wang M, Wu YM, Pan Z, et al. Predictors of futile recanalization in patients with large infarct: A post-hoc analysis of the ANGEL-ASPECT trial. Stroke Vasc Neurol. 2025 Oct;svn-2024-003382.

23. Yoshimoto T, Inoue M, Yamagami H, Fujita K, Tanaka K, Ando D, et al. Use of diffusion-weighted imaging-alberta stroke program early computed tomography score (DWI-ASPECTS) and ischemic core volume to determine the malignant profile in acute stroke. J Am Heart Assoc. 2019 Nov;8(22):e012558.

24. Yoshimura S, Sakai N, Yamagami H, Uchida K, Beppu M, Toyoda K, et al. Endovascular therapy for acute stroke with a large ischemic region. N Engl J Med. 2022 Apr;386(14):1303-13.

25. Zaidat OO, Kasab SA, Sheth S, Ortega-Gutierrez S, Rai AT, Given CA, et al. TESLA trial: rationale, protocol, and design. Stroke Vasc Interv Neurol. 2023;3:e000787.

26. Zhang X, Xie Y, Wang H, Yang D, Jiang T, Yuan K, et al. Symptomatic intracranial hemorrhage after mechanical thrombectomy in Chinese ischemic stroke patients: The ASIAN Score. Stroke. 2020 Sep;51(9):2690-96.

27. Zhou T, Yi T, Li T, Zhu L, Li Y, Li Z, et al. Predictors of futile recanalization in patients undergoing endovascular treatment in the DIRECT-MT trial. J Neurointerv Surg. 2022 Aug;14(8):752-5.