Large Core Thrombectomy: Feasibility of Simplified Protocol in Resource‐Limited Settings

Abstract

BACKGROUND

Several trials have demonstrated the benefits of endovascular thrombectomy (EVT) for large‐core strokes (Alberta Stroke Program Early CT [Computed Tomography] Score <6). However, its effectiveness in lower‐middle‐income countries with resource‐limited settings remains uncertain. This study evaluated the feasibility of EVT for large‐core strokes using a simplified imaging protocol with noncontrast CT and CT angiography in a resource‐constrained environment.

METHODS

We conducted a prospective, single‐center, observational study at Da Nang Hospital, Vietnam (May 2023–May 2024). Patients with anterior circulation large‐vessel occlusion strokes, Alberta Stroke Program Early CT Score <6 on noncontrast CT, admission National Institutes of Health Stroke Scale score ≥6, and EVT within 24 hours were included. The primary outcome was the modified Rankin Scale score at 90 days. Functional independence was defined as modified Rankin Scale score 0–2 and ambulatory independence as 0–3. Safety outcomes included symptomatic intracranial hemorrhage and 90‐day mortality. Post‐hoc indirect comparisons of ambulatory independence and mortality were made against the Large Stroke Therapy Evaluation EVT arm and the best medical treatment cohorts from 6 published “large core” randomized controlled trials.

RESULTS

Among 157 EVT‐treated patients, 52 (33.1%) had Alberta Stroke Program Early CT Score <6. Median age was 62.5 years, and 57.7% were male. Median onset‐to‐hospital time was 4.1 hours, admission National Institutes of Health Stroke Scale score15, and initial Alberta Stroke Program Early CT Score was 4. Successful reperfusion (modified Treatment in Cerebral Infarction≥2b) was 78.9%. At 90 days, the median modified Rankin Scale score was 3.5. Functional and ambulatory independence were 23.1% and 50%, respectively. Symptomatic intracranial hemorrhage occurred in 9.6%, mortality was 25%. Successful reperfusion was the only independent predictor of ambulatory independence (odds ratio [OR], 14.7; 95% CI, 1.6–134). Indirect comparisons showed higher ambulatory independence in our cohort compared with the Large Stroke Therapy Evaluation EVT arm (50.0% versus 33.5%, P = 0.033) and the pooled best medical treatment cohort from 6 published randomized controlled trials (50.0% versus 19.89%, P<0.001), with no significant mortality difference.

CONCLUSIONS

EVT is feasible for patients with large‐core stroke in lower‐income countries using a simplified noncontrast CT ‐CTA protocol. Successful reperfusion is a key determinant of improved outcomes.

CLINICAL TRIAL REGISTRATION INFORMATION

This study is a substudy of the multicenter PROMISE (Predictors of Good Outcomes in Thrombectomy for Large Infarct Core Stroke Evaluation) cohort, registered on ClinicalTrials.gov (NCT06016348, https://clinicaltrials.gov/study/NCT06016348), using data from patients enrolled at Da Nang Hospital.

Endovascular thrombectomy (EVT) is the gold standard for treating selected patients with acute ischemic stroke caused by large vessel occlusions. Current guidelines recommend the highest level of evidence for EVT in patients with acute large vessel occlusions who have a small to medium infarct core, defined by an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 6 or higher within a 24‐hour window. ¹ Patients with acute large infarct core (LIC) are not typically candidates for endovascular treatment, although they account for ∼25%. ² In recent years, the benefits of EVT for acute LIC stroke have been demonstrated in high‐quality trials. ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ However, these trials have been conducted exclusively in high‐ or upper‐middle‐income countries and have primarily relied on magnetic resonance imaging (MRI) or perfusion imaging for patients' selection.

In practical clinical scenarios, particularly in lower‐income countries with limited resources, advanced imaging modalities are not widely available in emergency situations. Noncontrast computed tomography (NCCT)–computed tomography angiography (CTA) is still the most practical and accessible imaging approach for stroke evaluation. Despite their widespread use, the application of NCCT‐based selection for EVT in large‐core infarct patients remains a subject of ongoing debate. Additionally, in these countries, comprehensive stroke centers are often overwhelmed, along with a lack of experience and robust evidence on the outcomes of large‐core thrombectomy, leading to cautious implementation in clinical practice. Consequently, the efficacy of large‐core thrombectomy has not been sufficiently proven and continues to be a subject of uncertainty in lower‐income countries.

NCCT is a simple, rapid, and readily available imaging modality for assessing early ischemic changes, making it a key part of stroke assessment in most centers worldwide. The TENSION (Efficacy and Safety of Thrombectomy In Stroke with Extended Lesion and Extended Time Window) trial demonstrated that NCCT‐based selection for EVT in patients with ASPECTS scores of 3–5 was effective within a 12‐hour window. ⁶ Similarly, although the TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke) trial yielded negative results for patients with ASPECTS of 2–5 in the 24‐hour window, it still suggests a potential role for thrombectomy using NCCT‐based selection within this timeframe. ⁸

Given the widespread availability of NCCT and its practicality in resource‐limited settings, its role in guiding EVT decisions for patients with LIC warrants further investigation. In this single‐center, real‐world observational study conducted in Vietnam–a lower‐middle‐income country–we aimed to evaluate the efficacy and safety of EVT within 24 hours in patients with nonrestrictive acute large‐core stroke (ASPECTS<6) based on NCCT selection.

METHODS

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Nonstandard Abbreviations and Acronyms

LASTE

Large Stroke Therapy Evaluation

LIC

large infarct core

CLINICAL PERSPECTIVE

What Is New?

• This study demonstrates the feasibility of endovascular thrombectomy for large‐core infarct strokes (Alberta Stroke Program Early Computed Tomography Score<6) in a resource‐limited setting using a simplified imaging protocol with noncontrast computed tomography and computed tomography angiography. The results indicate that successful reperfusion (modified Treatment in Cerebral Infarction≥2b) is a key determinant of improved outcomes.

What Are the Clinical Implications?

• Noncontrast computed tomography‐computed tomography angiography‐based selection is a feasible alternative to advanced imaging for endovascular thrombectomy in large‐core infarct patients, particularly in low‐resource settings, expanding treatment access. Successful reperfusion remains the key determinant of improved outcomes, emphasizing the importance of optimizing endovascular thrombectomy strategies in resource‐limited settings.

Study Design and Eligible Patients

This study was designed as a prospective, single‐center, observational study over a 1‐year period from May 2023 to May 2024, conducted at Da Nang Hospital, Vietnam. The data for this analysis were derived from patients enrolled at our center as part of the multicenter PROMISE (Predictors of Good Outcomes in Thrombectomy for Large Infarct Core Stroke Evaluation) cohort (ClinicalTrials.gov Identifier: NCT06016348). A detailed list of the primary resources and clinical scales used in this study is provided in Supplemental Materials (Table S1).

Inclusion criteria were age ≥18; acute ischemic stroke due to large vessel occlusion in the anterior circulation, confirmed by CTA showing occlusion of the internal carotid artery or the M1 segment of the middle cerebral artery, or tandem occlusion; LIC, defined as an ASPECTS<6 on NCCT at admission; moderate to severe neurological deficit, with an admission National Institutes of Health Stroke Scale (NIHSS) score≥6; underwent EVT within 24 hours from symptom onset. Exclusion criteria were prestroke disability (mRS score≥3); multiple or bilateral ischemic strokes; severe or end‐stage medical conditions; severe coagulation disorders; and inability to provide consent or follow‐up.

The primary efficacy outcome was evaluated by the mRS at 90 days post EVT. Functional independence was defined as an mRS score of 0–2, and ambulatory independence was described as an mRS score of 0–3. Safety outcomes included symptomatic intracranial hemorrhage, as per the SITS‐MOST (Safe Implementation of Thrombolysis in Stroke‐Monitoring Study) criteria, ⁹ and the overall mortality within 90 days.

ASPECTS was initially assessed by 2 board‐certified neurologists and subsequently confirmed by an experienced radiologist in case of disagreement. Early neurological deterioration was defined as an increase in the NIHSS score by ≥ 4 points within 24 hours after thrombectomy. Collateral score was evaluated using the Tan et al. score (0–3), which classifies collaterals as “good” if they are seen in ≥50% of the middle cerebral artery territory based on CTA. ¹⁰

A 2‐step imaging protocol using NCCT and CTA was applied for patient selection (Figure S1). No MRI or perfusion imaging was required. Recombinant tissue plasminogen activator was considered for patients presenting within the 4.5‐hour time window, with administration determined at the discretion of the treating physician. EVT techniques were performed at the discretion of the neurointerventionist. The degree of reperfusion was assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) scale, with successful reperfusion defined as mTICI≥2b. ¹¹ The 90‐day follow‐up mRS assessment was conducted via telephone or during outpatient visits.

This study was approved by the Ethics Committee of Da Nang Hospital (institutional review board No. 2449/BVDN‐HDYD). Informed consent was obtained from patients or their family members before inclusion in the study. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.

Statistical Analysis

All statistical analyses were conducted using Stata 17 (StataCorp LLC, College Station, TX, USA). Continuous variables were expressed as medians with interquartile ranges (IQRs), and categorical variables were presented as frequencies and percentages. Group comparisons were performed using the chi‐square test or Fisher's exact test for categorical variables and the Mann–Whitney U test or independent t‐test for continuous variables, depending on data distribution. To determine independent predictors of favorable outcomes (mRS score 0–3 at 90 days), multivariable logistic regression analysis was conducted, adjusting for potential confounders. Patient characteristics were analyzed and compared across time windows (<6 hours versus >6 hours), ASPECTS (0–2 versus 3–5), and mTICI (0–2a versus 2b–3) to identify differences between subgroups. Additionally, post‐hoc indirect comparisons of 90‐day ambulatory independence (mRS score 0–3) and mortality between our EVT cohort and 2 external groups were performed. The primary comparison was with the EVT arm of the LASTE (Large Stroke Therapy Evaluation) trial ⁷ owing to similar patient characteristics, given the inclusion of patients in a similar time window with an ASPECTS of 0–5 on unenhanced CT. This comparison was performed to indirectly assess the safety of the intervention in this cohort when compared to a closely matched cohort. A second comparison was conducted against a pooled best medical treatment cohort from 6 randomized controlled trials (Liu et al.) ¹² to indirectly assess efficacy against a more broadly matched cohort, where efficacy may be more variable (and higher) than in the BMT arm of LASTE alone. Data for both comparisons were analyzed using a 2‐sample test of proportion and results were interpreted with caution due to the unadjusted and indirect nature of these analyses. Statistical significance was set at P<0.05.

RESULTS

Patient Characteristics

From May 2023 to May 2024, we screened 157 patients with acute ischemic stroke due to large vessel occlusions who underwent EVT within 24 hours of stroke onset. Of these, 52 patients (33.1%) had LIC with an ASPECTS of <6 and met the study criteria. The 90‐day follow‐up was completed in August 2024, with no missing data for the primary outcome.

The median age was 62.5 years (IQR 58.5–71), and 57.7% (30/52) of patients were men. The median NIHSS score at admission was 15 (IQR 13–19.75), and the median ASPECTS on NCCT before the procedure was 4 (IQR 3–4) (Table 1).

Table 1.

Baseline Characteristics

Characteristics of the patients	n = 52
Age, y–median (IQR)	62.5 (58.5–71.0)
Male sex–no.(%)	30 (57.7%)
Pre‐mRS–median (IQR)	0 (0‐0)
History–no.(%)
TIA/stroke	7 (13.5%)
Hypertension	42 (80.8%)
Atrial fibrillation	16 (30.8%)
Diabetes	6 (11.5%)
Anticoagulant	8 (15.4%)
Antiplatelet	10 (19.2%)
Baseline NIHSS score–median (IQR)	15.0 (13–19)
Systolic blood pressure–median (IQR)	140 (120–150)
Baseline ASPECTS–median (IQR)	4 (3–4)
0–2–no.(%)	11 (21.2%)
3–no.(%)	14 (26.9%)
4–no.(%)	15 (28.8%)
5–no.(%)	12 (23.1%)
Intravenous thrombolysis–no.(%)	16 (30.8%)
Occlusion site ‐ no.(%)
ICA	5 (9.6%)
M1 segment of MCA	33 (63.5%)
Tandem	14 (26.9%)
Collateral score–Median (IQR)	2 (1–2)
Stroke etiology–no.(%)
Large‐artery atherosclerosis	26 (50%)
Cardioembolic	18 (34.6%)
Undetermined or other	8 (15.4%)
Median time from onset to admission (IQR) (h)	4.1 (1.8–7.9)
$\le$6 h–no.(%)	35 (67.3%)
6–24 h–no.(%)	17 (32.7%)
Median duration (IQR) (min)
Door to needle time	40 (35–50)
Door to puncture time	111 (83.0–134.5)
Door to reperfusion	146.5 (124–185.5)

ASPECTS indicates Alberta Stroke Program Early CT [Computed Tomography] Score; ICA, internal carotid artery; IQR, interquartile range; MCA, middle cerebral artery; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; and TIA, transient ischemic attack.

Regarding ASPECTS distribution, 11 patients (21.2%) had ultra‐LIC (ASPECTS 0–2), and 41 patients (78.8%) had ASPECTS 3–5. The median time from the last known well to hospital admission was 4.1 hours (IQR 1.8‐7.9), with 32.7% (17/52) of patients presenting in the late window (beyond 6 hours from stroke onset).

Intravenous thrombolysis was used as a bridging therapy in 30.8% (16/52) of patients. Most patients had occlusions in the M1 branch of the middle cerebral artery, with 63.5% (33/52), internal carotid artery occlusions occurred in 9.6% (5/52), and tandem lesions in 26.9% (14/52). The median collateral score was 1 (IQR 1–2), with 44.2% (23/52) of patients having good collaterals. The median number of passes was 2 (IQR 1–3.5). Two patients (3.8%) underwent rescue intracranial angioplasty/stenting. Successful recanalization (mTICI≥2b) was achieved in 78.8% (41/52) of patients. The median door‐to‐puncture time was 110 minutes (IQR 83–134.5), and the median door‐to‐reperfusion time was 146.5 minutes (IQR 124–185.5).

Outcomes

At 90 days, the median mRS score was 3.5 (IQR 3–5.5) (Figure 1). Functional independence (mRS score 0–2) was achieved by 23.1% (12/52) of patients, and 50% (26/52) achieved an ambulatory outcome (mRS score 0–3) (Table 2). Early neurological deterioration occurred in 20 patients (38.5%). Decompressive craniectomy was performed in 5 patients (9.6%) within 7 days.

Figure 1.

Distribution of mRS scores at 90 days. mRS indicates modified Rankin Scale.

Table 2.

Efficacy and Safety Outcomes and Treatment Effects

Outcomes	n = 52
Functional outcome
Median mRS score at 90 d (IQR)	3.5 (3–5.5)
mRS score 0–2 at 90 d–no. (%)	12 (23.1%)
mRS score 0–3 at 90 d–no. (%)	26 (50%)
Safety outcomes
Symptomatic intracranial hemorrhage–no.(%)	5 (9.6%)
Any intracranial hemorrhage–no.(%)	31 (59.6%)
Death within 90 d–no.(%)	13 (25%)
Early neurological deterioration–no.(%)	20 (38.5%)
Decompressive hemicraniectomy–no.(%)	5 (9.6%)
Treatment effects
Final mTICI–no.(%)
0–2a	11 (21.2%)
2b‐3	41 (78.8%)
Median pass of EVT (IQR)	2 (1.0–3.5)
Median NIHSS score at 24 h (IQR)	17.5 (12.0–24.0)
Median NIHSS score at 7 d or discharge (IQR)	15.0 (9.0–31.0)

EVT indicates endovascular thrombectomy; IQR, interquartile range; mRS, modified Rankin scale; mTICI, modified Treatment in Cerebral Infarction; and NIHSS, National Institutes of Health Stroke Scale.

Regarding safety outcomes, any intracerebral hemorrhage within 24 hours after EVT occurred in 59.6% (31/52) of patients, and symptomatic intracerebral hemorrhage was observed in 5 patients (9.6%). The mortality rate was 25% (13/52).

Multivariable logistic regression analysis identified successful recanalization as the only factor independently associated with ambulatory independence (mRS score 0–3; odds ratio [OR] 14.7, 95%CI 1.6–134), after adjusting for age, admission NIHSS score, and door‐to‐groin time (Table S2).

A significant difference in 90‐day mRS scores was observed between the successful group (median 3, IQR 2–4) and unsuccessful recanalization (median 6, IQR 5–6, P = 0.0008) (Table S3). The rate of ambulatory independence was 61% (25/41) versus 9.1% (1/11), respectively (P = 0.005) (Figure 2). The mortality rate was significantly lower in the successful recanalization group, 17.1% (7/41), compared with the unsuccessful recanalization group, 54.6% (6/11), with P = 0.019. Although any intracerebral hemorrhage and symptomatic intracerebral hemorrhage occurred more frequently in the successful recanalization group, the difference was not statistically significant.

Figure 2.

Comparison of ambulatory independence across subgroups. ASPECTS indicates Alberta Stroke Program Early CT [Computed Tomography] Score; mRS, modified Rankin Scale; and mTICI, Modified Treatment in Cerebral Infarction.

In the ASPECTS 3–5 group, 58.5% (24/41) of patients achieved an ambulatory outcome, compared with 18.2% (2/11) in the ASPECTS 0–2 group (P = 0.017) (Figure 2). The ASPECTS 0–2 group also had higher rates of death, symptomatic intracerebral hemorrhage, and any intracerebral hemorrhage compared with the ASPECTS 3–5 group. We found no significant differences between the early (≤6 hours) and late window (>6 hours) groups in an ambulatory outcome [54.3% (19/35) versus 41.2% (7/17), respectively, P = 0.375] as well as other safety outcomes (Figure 2).

Post‐hoc indirect comparative analyses showed that our EVT cohort (n = 52) had higher ambulatory independence at 90 days compared with the EVT arm of the LASTE trial ⁷ (50.0% versus 33.5%, P = 0.033) and lower, though nonsignificant, mortality (25.0% versus 36.1%, P = 0.141). Compared with the pooled BMT cohort from Liu et al., ¹² ambulatory independence was also significantly higher (50.0% versus 19.89%, P<0.001), with a trend toward lower mortality (25.0% versus 36.80%, P = 0.085).

DISCUSSION

Our study provides real‐world evidence suggesting that endovascular thrombectomy, guided by a simplified NCCT‐CTA imaging protocol, is a feasible therapeutic option for patients with LICs in resource‐limited settings.

Although EVT has been established as effective for LICs within a 24‐hour window in well‐resourced countries through large clinical trials, its application under resource constraints warrants specific investigation. The meta‐analysis of 6 large clinical trials showed that EVT compared with BMT was associated with improved mRS score at 90 days (generalized OR, 1.6, 95% CI 1.4–1.8) and higher odds of independent ambulation (risk ratio 1.9; 95% CI 1.5–2.5), further validating EVT's role in patients with LICs. ¹² NCCT is the most commonly available stroke imaging modality worldwide, and its speed, accessibility, and cost‐effectiveness make it a valuable tool for EVT decision‐making. NCCT is not only applicable within the standard 6‐hour window but has also been proven noninferior to advanced imaging and is broadly accepted for selecting patients with large vessel occlusion and non‐LIC in the extended 6‐ to 24‐hour window, making it a viable alternative in centers with limited access. ¹³ , ¹⁴ In our study, NCCT was used to assess LIC volume with ASPECTS<6, and CTA confirmed vessel occlusion, eliminating the need for advanced imaging. The feasibility of this approach is essential for expanding EVT eligibility in lower‐resource stroke centers, where MRI and CT perfusion are often unavailable or impractical due to cost, infrastructure limitations, and prolonged acquisition times in an already overwhelmed emergency setting. The TENSION trial, which exclusively used NCCT‐based ASPECTS (3–5) selection, confirmed that EVT is beneficial in patients with LICs without the need for MRI or perfusion imaging. ⁶ When comparing our results with other large randomized controlled trials (Table 3), the functional independence rate (mRS score 0–2 at 90 days) in large‐core trials has ranged from 13.3% to 30%, and our study's 23.1% functional independence rate aligns with these findings. The results in this study were particularly comparable to the ANGEL‐ASPECT (Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core) trial in terms of ambulatory outcomes and were better than other trials, with 50% of patients achieving mRS score 0–3 at 90 days. This is likely due to similarly lower baseline NIHSS scores and a younger patient cohort, which may have contributed to improved recovery potential. Another important aspect of our study is the treatment time window, as the majority of our patients (65.4%) underwent EVT within 6 hours of symptom onset, a higher proportion than in other trials. This is particularly relevant as recent meta‐analyses suggest that EVT effectiveness may decline in late‐window patients, underscoring the need to explore whether NCCT‐based selection remains valid beyond the conventional 6‐hour window. ¹⁵

Table 3.

Baseline Characteristics and Outcomes of Large Core Thrombectomy Trials and This Study

	Yoshimura et al. RESCUE‐JAPAN LIMIT n = 101	A. Sarraj et al. SELECT2 n = 178	Huo et al. ANGEL‐ASPECT n = 230	Bendszus et al. TENSION n = 125	V. Costalat et al. LASTE n = 159	Zaidat et al. TESLA n = 152	This study n = 52
Study location	Japan	North America, Australia	China	Europe, Canada	Europe	United States	Vietnam
Median age (IQR) (y)	76.6 (SD 10)	66 (58–75)	68 (61–73)	73 (65–81)	73 (66–79)	65.5 (54–74)	62.5 (58.5–71)
Sex: male, n (%)	55 (54.5)	107 (60.1)	135 (58.7)	59 (55)	82 (51.6)	77 (50.7)	30 (57.7)
Time from onset to randomization or admission, median (IQR), min	229 (144–459) (random) 190 (85–390) (admission)	544 (316–920) NR	453 (299–712) 338 (199–629)	120 (72–210) NR	271 (199–351) NR	652.5 (333–942) NR	245 (107.5–469.5)
Time window <6h≥6h	71 (70.3) 30 (29.7)	NR	82 (35.7) 148 (64.3)	78 (62.4) 47 (37.6)	NR	42 (27.6) 110 (72.4)	35 (67.3) 17 (32.7)
ASPECTS baseline median (IQR)	3 (3–4)	4 (3–5)	3 (3–4)	4 (3–5)	2 (1–3)	4 (3–5)	4 (3–4)
NIHSS at admission median (IQR)	22 (18–26)	19 (15–23)	16 (13–20)	19 (16–22)	21 (18–24)	19 (15–23)	15 (13–19.75)
IVT, n (%)	27 (26.7)	37 (20.8)	66 (28.7)	49 (39)	55 (34.6)	31 (20.4)	16 (30.8)
mTICI 2b/3, n (%)	86/100 (86)	142 (79.8)	183/226 (81)	104 (83)	130/151 (86.1)	107/146 (73.3)	41 (78.8)
mRS score at 90 d median (IQR)	NR	4 (3–6)	4 (2–5)	4 (3–6)	4 (3–6)	5 (3–6)n = 151	3.5 (3–5.5)
mRS score 0–2 at 90 d, n (%)	14 (14)	36 (20.3)	69 (30)	21/124 (17)	21/158 (13.3)	22/151 (14.6)	12 (23.1)
mRS score 0–3 at 90 d, n (%)	31 (31)	67 (37.9)	198 (47)	39/124 (31)	53/158 (33.5)	45/151 (29.8)	26 (50)
Mortality at 90 d, n (%)	18 (18)	68 (38.4)	50 (21.7)	49 (40)	57/158 (36.1)	53/150 (35.3)	13 (25)
sICH (SITS‐MOST), n (%)	9 (9)	1 (0.6)	14 (6.1) (HBC)	7 (5)* (HBC)	5/157 (3.2) 15/157 (9.6) HBC	6/151 (4)	5 (9.6)
Any intracranial hemorrhage, n (%)	58 (58)	NR	113 (49.1)	68/124 (54.8)	113/157 (72)	86/148 (58.1)	31 (59.6)
Decompression, n (%)	10 (10)	NR	17 (7.4)	11 (9)	14 (8.8)	33 (21.9)	5 (9.6)

ANGEL ASPECT indicates Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core; ASPECTS, Alberta Stroke Program Early CT [Computed Tomography] Score; HBC, Heidelberg Bleeding Classification; IVT, intravenous thrombolysis; mRS, modified Rankin Scale; mTICI, Modified Treatment in Cerebral Infarction; NIHSS, National Institutes of Health Stroke Scale; NR, Not Reported; RESCUE‐JAPAN LIMIT, Recovery by Endovascular Salvage for Cerebral Ultra‐acute Embolism Japan Large Ischemic core Trial; SELECT2, A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke; sICH, symptomatic intracranial hemorrhage; SITS‐MOST, Safe Implementation of Thrombolysis in Stroke‐Monitoring Study; TENSION, Efficacy and Safety of Thrombectomy In Stroke with Extended Lesion and Extended Time Window; and TESLA, Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke.

In terms of safety, this study reported an overall intracerebral hemorrhage rate of 59.6% and a symptomatic intracerebral hemorrhage rate of 9.6%, comparable to other large clinical trials, particularly in Asia (RESCUE‐JAPAN LIMIT [Recovery by Endovascular Salvage for Cerebral Ultra‐acute Embolism Japan Large Ischemic core Trial]: 9%, ANGEL‐ASPECT: 6.1%). ³ , ⁵ This finding is crucial, as concerns about hemorrhagic risk have been a major barrier to expanding EVT in patients with LICs. Additionally, our study found a 25% mortality rate, which was lower than in Western trials (SELECT2 [A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke], TENSION, LASTE, TESLA) and similar to Asian trials (RESCUE‐JAPAN LIMIT, ANGEL‐ASPECT), indicating that NCCT‐based selection is a reliable approach and did not appear to increase mortality risk in our cohort compared with these trials. These findings suggest that simplified EVT protocols based on NCCT‐CTA could be adopted in low middle‐income countries to expand access to thrombectomy, even for patients with LICs.

Our study also highlighted that successful recanalization (mTICI≥2b) was the strongest predictor of favorable outcomes. This finding is consistent with previous studies that emphasize the central role of achieving optimal reperfusion in determining EVT success, irrespective of infarct core size. A retrospective analysis of data from the German Stroke Registry also showed similar results, with 348 patients with LICs, of whom 83.3% achieved mTICI 2b–3 recanalization. The successful reperfusion (mTICI 2b–3) group demonstrated better functional outcomes and lower mortality compared with the unsuccessful reperfusion group (mTICI 0–2a). ¹⁶ A recently published multicenter retrospective aggregate cohort study on large ischemic volume thrombectomy further confirmed that the successful recanalization group had a significantly higher rate of favorable functional outcome (mRS score 0–3) than the unsuccessful recanalization group (47.6% versus 15.3%; OR, 5.02; 95% CI, 2.87–8.76; P<0.01). ¹⁷ That study also demonstrated a significant reduction in mortality with successful recanalization, without an associated increase in the rate of symptomatic intracranial hemorrhage. ¹⁷ These findings underscore the importance of achieving reperfusion to preserve salvageable tissue, which may play a more significant role in functional recovery than the initial infarct core volume. Collectively, they provide compelling evidence that successful recanalization is a key determinant of improved functional outcomes and reduced mortality, even in patients with LICs.

Extended thrombectomy to the 24‐hour window has been demonstrated in clinical trials since 2018. ¹⁸ , ¹⁹ In recent years, a simple selection protocol using NCCT‐CTA for thrombectomy in the late window (beyond 6 hours) has shown effectiveness in patients with small to medium‐sized infarct cores (ASPECTS ≥6). ¹³ , ²⁰ Two NCCT‐based clinical trials have explored extending the endovascular treatment window for patients with LICs. ⁶ , ⁸ The TENSION trial showed benefit for ASPECTS 3–5 within 12 hours, ⁶ whereas TESLA (ASPECTS 2–5, up to 24 hours) did not meet its primary endpoint but suggested potential efficacy. ⁸ In our study, the ambulatory outcome in late‐window patients (41.2%) was comparable to early‐window patients, with no increase in symptomatic intracranial hemorrhage or mortality. However, the number of patients in the late window, particularly those treated 12–24 hours after stroke onset, which limits generalizability. Regarding ultra‐large cores (ASPECTS 0–2), our findings indicated poor outcomes despite EVT, suggesting that expanding treatment to this subgroup may not be appropriate.

To contextualize our findings, post hoc indirect comparisons were performed with the EVT arm of the LASTE trial ⁷ and a pooled BMT cohort from 6 randomized controlled trials (Liu et al. ¹² ). Our EVT cohort showed a higher rate of 90‐day ambulatory independence (50.0%) compared with both the LASTE EVT group (33.5%, P = 0.033) and the BMT cohort (19.89%, P<0.001). Mortality in our cohort (25.0%) was not statistically different from the LASTE EVT (36.1%, P = 0.141) and BMT groups (36.8%, P = 0.085). These observations, particularly the higher rate of functional independence, are encouraging. However, they warrant cautious interpretation. Although both studies enrolled patients without restricting infarct core size, our cohort was younger and had lower NIHSS scores and higher ASPECTS, all factors linked to better prognosis. Additionally, our study used NCCT‐CTA for selection, whereas LASTE mostly used MRI, potentially influencing patient profiles. As a single‐center, observational study, selection bias likely contributed to the favorable outcomes observed. Although the comparison with BMT suggests a potential benefit of EVT in our setting, the inherent limitations of indirect comparisons across trials with differing methodologies, populations, and imaging strategies must be acknowledged. These exploratory analyses primarily highlight the feasibility and potential effectiveness of our simplified imaging protocol and underscore the need for prospective, controlled studies in similar resource‐limited environments.

Based on the results of this study, our findings suggest that applying the NCCT‐CTA protocol for EVT in patients with LICs is feasible in our limited‐resource setting and is associated with encouraging outcomes and an acceptable safety profile. This is particularly meaningful for countries and centers with limited resources, as it helps expand EVT eligibility for more patients with stroke, providing them with greater treatment opportunities. However, several limitations should be acknowledged. First, this was a single‐center study, which may limit the generalizability of our findings to other hospitals with different stroke care infrastructures. Second, our sample size was relatively small (n = 52), highlighting the need for larger multicenter studies to confirm these results, especially in special patient subgroups, such as the late‐window patients (beyond 6 hours) or those with ultra‐LICs (ASPECTS 0–2). Third, our study lacked a control group of patients with LICs who did not undergo EVT, preventing a direct comparison between EVT and medical management alone. Future comparative studies are needed to further validate the effectiveness and safety of EVT in patients with LICs, particularly in resource‐limited settings in low‐middle‐income countries. Fourth, and importantly, selection bias is a significant limitation. As an observational study, patients may have been selected based on a higher likelihood of favorable outcomes despite large infarcts. This potential bias could influence observed outcomes and complicate comparisons with other trial populations, warranting cautious interpretation.

CONCLUSION

Our findings suggest that NCCT‐CTA‐based selection is a feasible alternative to advanced imaging for EVT in patients with LICs, particularly in low‐resource settings. The results indicate that NCCT may be a reliable tool to guide EVT decision‐making, with functional outcomes and safety profiles that appear comparable to those reported in trials using advanced imaging modalities. Our findings also highlight that successful reperfusion (mTICI ≥2b) remains the strongest predictor of favorable outcomes, reinforcing its crucial role in improving functional recovery and reducing mortality, even in patients with LICs selected by NCCT.

Sources of Funding

There was no funding for this study.

Disclosure

None.

Supporting information

Supporting Information

Table S1: The Major Resource Table

Table S2: Results of binary logistic regression analysis for factors associated with ambulatory independence (mRS score 0–3)

Table S3: Characteristics of the patients by reperfusion status

Figure S1: Acute stroke protocol at Da Nang Hospital