Long-term efficacy and safety of endovascular thrombectomy for acute ischemic stroke with large vessel occlusion: a systematic review and meta-analysis

Abstract

Background:

Endovascular thrombectomy (EVT) improves functional outcomes at 90 days in patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO). However, its long-term efficacy and safety beyond 90 days remain unclear.

Objective:

We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of EVT plus best medical treatment (BMT) versus BMT alone beyond 90 days in patients with AIS and LVO.

Methods:

PubMed, Embase, and Cochrane Central databases were searched to identify randomized controlled trials (RCTs) comparing EVT plus BMT versus BMT alone in AIS patients with LVO. Primary outcomes included functional independence (mRS ≤2), independent ambulation (mRS ≤3), death or dependency (mRS 4–6), and all-cause mortality beyond 90 days. We applied a random-effects model and pooled risk ratios (RRs) along with 95% confidence intervals (CIs) using the Cochrane RoB2 tool for assessing risk of bias in randomized trials.

Results:

Seven RCTs with 2358 patients (56% males) were included. The mean age of the patients was 69.5 years and mean follow-up duration was 1.2 years. The results showed that EVT combined with BMT improved functional independence (mRS ≤2) (RR 2.08, CI: 1.55–2.80; P < 0.00001), independent ambulation (mRS ≤3) (RR 1.71, CI: 1.36–2.15; P < 0.00001), and quality of life (SMD 0.36; CI: 0.19–0.54; P < 0.00001) beyond 90 days compared to BMT alone. Moreover, the EVT plus BMT group also had a significantly reduced death or dependency (mRS 4–6) (RR 0.78, CI: 0.73–0.84; P < 0.00001) and all-cause mortality (RR 0.83, CI: 0.76–0.90; P < 0.0001) beyond 90 days than the BMT group. All RCTs were rated as having a low risk of bias.

Conclusion:

EVT combined with BMT significantly improves long-term functional outcomes and quality of life and reduces mortality in AIS patients with LVO compared to BMT alone.

Key recommendations for Future Research:

• Multicenter validation of endovascular thrombectomy (EVT) outcomes in diverse patient populations.

• Standardized reporting guidelines for EVT studies.

• Inclusion of patients with low Alberta Stroke Program Early CT (ASPECT) scores and large ischemic cores.

• Control for and report post-EVT factors like rehabilitation protocols, medication adherence, follow-up care, and lifestyle modifications.

• Large-scale randomized controlled trials with diverse patient populations.

• Investigation of optimal treatment windows and imaging criteria for EVT.

Introduction

Acute ischemic stroke (AIS) accounts for approximately 87% of all strokes and is the fifth leading cause of death in the USA^[1]. It is a critical medical emergency characterized by sudden loss of blood flow to the brain, leading to significant morbidity and mortality^[2]. Large vessel occlusion (LVO) is a specific type of AIS characterized by the blockage of one of the major cerebral arteries, resulting in significant damage to brain tissue. It is reported that the mean prevalence of LVO in patients with AIS is found to be 31.1%. The presence of LVO in AIS patients results in worse functional outcomes than in patients with occlusion of proximal arteries, highlighting the need for timely intervention and management^[3]. In this regard, endovascular therapies are of utmost importance, as these occlusions can lead to severe brain tissue damage if not promptly addressed. Clinical trials have reported that endovascular therapies show positive functional outcomes as compared to standard medical therapy^[4]. Additionally, endovascular therapies can be performed within a timeframe of 6–12 hours post-symptom onset, allowing speedy recovery of brain tissue and saving it from irreversible damage^[4].

Endovascular thrombectomy (EVT), a specific type of endovascular therapy, has emerged as a critical intervention for AIS patients with LVO over the last few decades^[4,5]. EVT has been shown to result in better clinical outcomes than in patients who did not receive this intervention; it has also decreased mortality rates among patients with LVO^[5]. Pivotal trials including SWIFT PRIME, EXTEND-IA, and REVASCAT established the effectiveness of EVT, mainly when it is performed within the first 6 hours of stroke onset^[1]. It is considered the standard treatment for anterior circulation stroke due to LVO^[6]. However, recent studies have also demonstrated its efficacy in posterior circulation strokes^[7].

Assessing outcomes beyond the 90-day period in AIS patients treated with EVT is crucial for understanding the sustained benefits and potential late complications of this treatment. A longer follow-up duration beyond 90 days offers crucial insights into sustained recovery, potential delayed benefits, and late adverse effects in EVT-treated patients, ultimately informing clinical decision-making, patient counseling, and secondary prevention strategies. This information can inform clinical decision-making, enabling healthcare providers to tailor treatment plans and rehabilitation strategies to individual patients’ needs. Moreover, longer-term outcome data can optimize resource allocation, improve patient care, and enhance the design of future clinical trials. By evaluating outcomes beyond 90 days, clinicians and researchers can gain a more comprehensive understanding of the benefits and limitations of EVT, ultimately leading to improved patient outcomes and quality of life.

Clinical outcomes of AIS are typically assessed by the modified Rankin Scale (mRS) at 90 days^[8–10]. Multiple studies have reported improved functional outcomes, including functional independence and independent ambulation, at 90 days post-EVT^[11,12]. However, uncertainties remain regarding EVT’s benefits in AIS patients with different infarct sizes, especially beyond the 90-day period. Recently published trials on the long-term outcomes of EVT have demonstrated its efficacy and safety beyond 90 days as well^[8,9]. Our objective was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) focusing on the long-term follow-up of EVT beyond 90 days in AIS patients with LVO.

Methods

This systematic review and meta-analysis were performed in alignment with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Cochrane Handbook for Systematic Reviews of Interventions^[13,14]. This review has been reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (assessing the methodological quality of systematic reviews) guidelines. The protocol of this review has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) with identifier CRD42024580763.

HIGHLIGHTS

• Improved long-term functional outcomes: Endovascular thrombectomy (EVT) plus best medical treatment (BMT) significantly improved functional independence (mRS ≤2) and independent ambulation (mRS ≤3) beyond 90 days in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO).

• Enhanced quality of life and reduced mortality: EVT combined with BMT also improved quality of life and reduced death or dependency (mRS 4–6) and all-cause mortality beyond 90 days compared to BMT alone.

• Low risk of bias and consistent results: The systematic review and meta-analysis included seven randomized controlled trials with 2358 patients, and all trials were rated as having a low risk of bias. The results consistently demonstrated the long-term efficacy and safety of EVT plus BMT in AIS patients with LVO.

Eligibility criteria

The studies were included if they met the following eligibility criteria: (1) RCTs; (2) enrolling AIS patients with LVO; (3) comparing EVT plus medical therapy with medical therapy alone; (4) follow-up duration ≥6 months; and (5) reporting at least one of the outcomes of interest. Our literature search included studies published in any language, with no restrictions. Studies without a control group, non-RCTs (case reports, case series, observational studies, reviews), non-human studies, preliminary reports, and studies not reporting any of the primary study outcomes were excluded.

Search strategy and data extraction

A systematic literature search was performed across PubMed, Embase, and Cochrane Central spanning from inception to 12 January 2025. The Medical Subject Headings (MeSH) keywords employed included “thrombectomy,” “endovascular thrombectomy,” “mechanical thrombectomy,” “ischemic stroke,” “acute ischemic stroke,” “cerebrovascular accident,” “stroke,” and “randomized controlled trial.” Additionally, the reference lists of all selected articles were scrutinized for other potential studies. The detailed search strategy is provided in Supplementary Digital Content Table 1, available at: http://links.lww.com/MS9/A917.

All studies obtained from our search were imported into EndNote v20, with duplicates subsequently eliminated. Two independent authors evaluated the titles and abstracts of all studies, excluding those that failed to fulfill our inclusion criteria. The remaining articles underwent eligibility assessment through a review of their full texts. Any disagreements were deliberated and resolved by consensus or the involvement of a third author.

Two researchers independently extracted data into a pre-established data collection template using Microsoft Excel. The data extracted from the studies included: study title, lead author’s name, year of publication, study setting, total number of participants, and each treatment cohort. Patient characteristics were also documented, including demographic factors such as age and gender, alongside comorbid conditions, which included diabetes, hypertension, atrial fibrillation, heart failure, as well as disease characteristics like the National Institutes of Health Stroke Scale (NIHSS) score upon admission.

Endpoints and subgroup analysis

The primary efficacy outcomes evaluated beyond 90 days included functional independence (mRS score ≤2) and independent ambulation (mRS score ≤3). The primary safety outcomes assessed were all-cause mortality, and death or dependency (mRS 4–6) beyond 90 days. Moreover, secondary outcomes of our study included mean mRS score and quality of life (EQ-5D index score).

Subgroup analysis were performed to assess the effectiveness of EVT in patients stratified by Alberta Stroke Program Early CT Score (ASPECTS >6 vs. ASPECTS <5) and different follow-up periods (12 and 24 months).

Quality assessment

Quality assessment of the included RCTs was performed by two independent authors using the Revised Cochrane risk of bias tool for RCTs (RoB2)^[15]. The studies were categorized as exhibiting low risk, some concerns, or high risk of bias based on their randomization methodology, deviations from the intended interventions, missing outcome data, measurement of outcomes, and any reporting biases. Any inconsistencies in the bias evaluation were addressed and reconciled with the aid of a third author.

Statistical analysis

Pooled risk ratios (RRs) accompanied by 95% confidence intervals (CIs) were computed for dichotomous outcomes. The Mantel–Haenszel method utilizing a random effects model was employed to consolidate the RRs. Cochrane Q test and I² statistics were implemented to detect any significant heterogeneity across the various trials and between subgroups. The Cochrane Handbook for Systematic Reviews of Interventions, section 10.10^[15], was referenced for the interpretation of I² values. The statistical analysis was performed using Review Manager (RevMan, Version 5.4; The Cochrane Collaboration, Copenhagen, Denmark) software.

Results

Study selection

The initial search yielded 1583 articles. After the removal of duplicates, 926 articles were assessed for eligibility based on the inclusion criteria. Based on initial screening of titles and abstracts 875 articles were excluded, and the remaining 51 articles were selected for full-length review. Ultimately, 7 RCTs were selected for inclusion in the meta-analysis^[16–22]. The details of the screening process are provided in Figure 1 in the form of PRISMA flowsheet. See Supplementary Digital Content, available at: http://links.lww.com/MS9/A918 files for PRISMA and AMSTAR checklist.

Figure 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) flow chart of the screening process.

Baseline characteristics

Seven RCTs with a total of 2358 patients (1236 in the EVT group and 1122 in the BMT group) were included. Among the patients, 56% were male. Three studies had patients with ASPECTS of less than 5 (large sized infarcts)^[17–19] while the other four studies included patients with ASPECTS >6 (mild to moderate ischemic infarcts)^[16,20–22]. Regarding the arterial tertiary involvement, three of the studies had both internal carotid artery (ICA) and middle cerebral artery (MCA) involvement^[17–19], three studies had mainly MCA involvement^[20–22], and one study had basilar artery involvement leading to stroke^[16]. The detailed characteristics of all the included RCTs are provided in Table 1.

Table 1.

Baseline characteristics of included studies

Study	No of patients, n	Mean age in years (SD)	Male %	Follow-up (yr)	Aspect score at admission, median (IQR)		Occlusion location				Diabetes %	Hypertension %	Atrial fibrillation %	NIHSS at admission
					Intervention	Control	Internal carotid artery (%)	Middle cerebral artery M1 (%)	Middle cerebral artery M2 (%)	Basilar artery (%)				Intervention	Control
MR CLEAN-LATE 2024	502	72.86 (12.20)	48	2	9 (7–10)	8 (7–9)	2.3	52	31	N/R	14.8	52.1	20.8	10[6–15]	10[6–16]
TENSION 2024	253	72.8 (11.9)	51	1	N/R	N/R	30.8	67.5	0.39	N/R	23.3	80.7	33.6	19 (4.5001)	18.3515 (5.2486)
SELECT-2 2024	352	66.4 (12.6)	58.8	1	4 (3–5)	4 (4–5)	41.4	54.2	4.26	N/R	30.6	73.8	24.14	19 (5.9792)	18.6489 (5.2328)
LASTE 2024	324	72.8 (10.5)	52.4	0.5	2 (1–3)	2 (1–3)	44.1	55.2	NR	N/R	NR	NR	NR	21 (4.4888)	21 (4.4873)
ATTENTION 2024	330	66.1 (15.07)	68.8	1	9 (8–10)	10 (8–10)	N/R	N/R	N/R	100	N/R	N/R	N/R	23 (13−35)	25 (13−35)
MR CLEAN 2017	391	66.45(10.44)	58.5	2	9 (8–10)	9 (8–10)	0.5	64.9	7.41	N/R	13.8	NR	24.8	17.351 (5.2283)	18 (5.9745)
REVASCAT 2017	206	NR	52.9	1	7 (6–9)	8 (6–9)	0.4	63.5	8.73	N/R	19.9	65	34.9	17 (4.5113)	15.9443 (5.2632)

Efficacy outcomes

All included trials reported the primary efficacy outcome of functional independence (mRS score ≤2) and independent ambulation (mRS score ≤3) with Revascat 2017 trial reporting mRS score ≤2 at two intervals, both of which were considered as separate cohorts^[20]. The results showed that EVT combined with BMT significantly improved the likelihood of functional independence (mRS ≤2) (RR 2.08, CI: 1.55–2.80; P < 0.00001 I² = 71%) and independent ambulation (mRS ≤3) (RR 1.71, CI: 1.36–2.15; P < 0.00001, I² = 74%), for patients with AIS beyond 90 days compared with BMT alone. The results for the efficacy outcomes; functional independence (mRS ≤2) and independent ambulation (mRS ≤3) are shown in Figures 2 and 3, respectively.

Figure 2.

Forest plot showing that endovascular thrombectomy combined with best medical therapy is superior to best medical therapy (BMT) alone in achieving functional independence (mRS ≤2). (i) Revascat 2017 reported outcomes at both 6 months and 1 year and both were included in the analysis as separate cohorts.

Figure 3.

Forest plot showing that endovascular thrombectomy combined with best medical therapy is superior to best medical therapy (BMT) alone in achieving independent ambulation (mRS ≤3).

Safety outcomes

The safety outcomes of all-cause mortality, and death or dependency (mRS 4–6) were reported by seven and six trials, respectively. For all-cause mortality, fewer events were observed in the EVT group than the BMT group (492 vs. 524). The risk of all-cause mortality beyond 90 days was significantly lower in patients receiving EVT combined with BMT (RR 0.83, CI: 0.76–0.90; P < 0.0001, I² = 0%) than BMT alone. Similarly, the rate of death or dependency (mRS 4–6) (RR 0.78, CI: 0.73–0.84; P < 0.00001, I² = 0%) was also significantly reduced for the EVT group. The results for these outcomes are shown in Figures 4 and 5.

Figure 4.

Forest plot showing that endovascular thrombectomy combined with best medical therapy is associated with lower all-cause mortality compared to best medical therapy (BMT) alone.

Figure 5.

Forest plot showing that endovascular thrombectomy combined with best medical therapy is associated with lower risk of death or dependency (mRS 4–6) compared to best medical therapy (BMT) alone.

Secondary outcomes

The results for secondary outcomes of mean mRS score and quality of life showed that mean mRS was significantly higher in AIS patients receiving EVT plus BMT compared to the control group BMT alone (SMD −0.33; CI: −0.43 to −0.22; P < 0.00001; I² = 19%). The quality of life was also found to be significantly better in the EVT plus BMT group compared to BMT alone (SMD 0.36; CI: 0.19–0.54; P < 0.0001; I² = 66%). These results are shown in Figures 6 and 7.

Figure 6.

Forest plot showing that endovascular thrombectomy combined with best medical therapy results in a lower (better) mean modified Rankin Scale (mRS) score compared to best medical therapy (BMT) alone.

Figure 7.

Forest plot showing that endovascular thrombectomy combined with best medical therapy is associated with improved quality of life compared to best medical therapy (BMT) alone.

Subgroup analysis

Based on ASPECT score

The subgroup analysis was performed based on ASPECT score to assess the long-term efficacy of EVT for AIS patients with different sized ischemic infarcts. Among six trials involving anterior circulation stroke patients, two distinct cohorts emerged: three trials featured patients with large core ischemic infarcts (ASPECTS <5)^[17–19], while the remaining three trials involved patients with mild to moderately sized infarcts (ASPECTS >6)^[20–22]. The detailed subgroup analysis is given in Supplementary Digital Content Figure 1A–F, available at: http://links.lww.com/MS9/A917.

1. Functional independence (mRS score ≤2): The analysis showed that in patients receiving EVT plus BMT, a statistically significant likelihood of functional independence was observed in those with large core ischemic regions (ASPECTS <5) (RR 3.91, CI: 2.55–6.00; P < 0.00001, I² = 0%) than those with mild to moderate sized infarcts (ASPECT >6) (RR 1.47, CI: 1.26–1.73; P < 0.00001, I² = 0%). Shown in Supplementary Digital Content Figure 1A, available at: http://links.lww.com/MS9/A917.

2. Independent ambulation (mRS score ≤3): Patients with large core ischemic infarct (ASPECTS <5) receiving EVT plus BMT had a significantly greater likelihood (P = 0.03) of achieving independent ambulation (RR 2.31, CI: 1.80–2.96; P < 0.00001, I² = 0%) compared to those with mild to moderate sized ischemic regions (ASPECTS >6) (RR 1.31, 95% CI: 1.15–1.48; P < 0.0001, I² = 0%). Shown in Supplementary Digital Content Figure 1B, available at: http://links.lww.com/MS9/A917.

3. Quality of life: A greater improvement in quality of life was observed in patients with ASPECTS <5 (SMD 0.55; CI: 0.38–0.71; P < 0.00001; I² = 0%) than those with ASPECTS >6 (SMD 0.23; CI: 0.11–0.35; P < 0.0003; I² = 0%). Shown in Supplementary Digital Content Figure 1C, available at: http://links.lww.com/MS9/A917.

4. Other Outcomes: All other outcomes including all-cause mortality, death or dependency, and mean mRS score showed statistically insignificant differences between patients based on their ASPECT scores.

Based on duration of follow-up

A subgroup analysis was conducted to examine the impact of follow-up duration (1 year vs. 2 years) on outcomes. Among the seven included trials, one reported 6-month outcomes, four reported 1-year outcomes, and two reported 2-year outcomes. Notably, quality of life was significantly better at 1 year compared to 2 years. However, subgroup analyses for all other outcomes revealed no significant differences between 1-year and 2-year follow-up periods, indicating that the efficacy of EVT is consistent across different follow-up durations. The corresponding forest plots are presented in Supplementary Digital content, Figure 2A–F, available at: http://links.lww.com/MS9/A917.

Quality assessment

All of the included RCTs were rated as having low risk of bias. The quality assessment of the individual RCTs is shown in Supplementary Digital Content Table 2, available at: http://links.lww.com/MS9/A917. Due to the limited number of studies (<10) included in the analysis, publication bias could not be performed.

Discussion

Our systematic review and meta-analysis, including seven RCTs and 2358 patients, compared EVT plus BMT with BMT alone in patients with AIS with large vessel occlusion. Our findings demonstrated that patients receiving EVT combined with BMT had a statistically significant likelihood of achieving functional independence (mRS ≤2) and independent ambulation (mRS ≤3) beyond 90 days post-intervention compared to BMT alone. Additionally, safety outcomes, including all-cause mortality and death or dependency (mRS 4–6) beyond 90 days, were also significantly better in the EVT plus BMT group, suggesting it as superior to BMT alone. Secondary outcomes, including mean mRS score and quality of life, were also found to be statistically more significant in the EVT + BMT group than in the BMT group.

Our meta-analysis expands on previous findings from the meta-analysis by Mortezaei et al, which included two trials on long-term (1-year results) based on limited data, including an abstract from the LASTE trial^[17,23]. Our results were consistent with their meta-analyses, which showed that EVT leads to improved functional outcomes, including independent ambulation and functional independence, beyond 90-day period in patients with large ischemic stroke^[23]. However, regarding safety outcomes, they reported no statistically significant difference between the two groups in terms of mortality rate beyond 90-days, which contrasts with our findings of a lower mortality rate beyond 90 days for EVT groups. This difference could be attributed to the limited number of RCTs and data included in their meta-analysis. They also demonstrated that functional independence (mRS 0–2) in the EVT plus BMT group was higher at 90 days than at 1 year, suggesting that large ischemic stroke requires more time for recovery, and EVT results at long-term follow-up (beyond 90 days) may be better compared to short-term follow-up (within 90-day period).

The included studies in our meta-analysis lacked homogeneity, with seven trials featuring varying patient profiles and follow-up durations. Three trials involved patients with large infarcts (ASPECTS <5)^[17–19], while four included patients with mild to moderate infarcts (ASPECTS >6)^[16,20–22]. Follow-up durations ranged from 6 months to 2 years, with three trials reporting 1-year outcomes^[16,18,19]. The trials also differed in stroke location, with three involving both ICA and MCA involvement^[17–19], three mainly involving MCA^[20–22], and one involving basilar artery^[16]. Notably, high heterogeneity was observed in functional independence (I² = 64%) and independent ambulation (I² = 75%) outcomes. To address this, subgroup analyses stratifying by ASPECT score (>6 vs. <5) effectively resolved heterogeneity. For patients with an ASPECT score <5, heterogeneity reduced to 0% for both outcomes. In contrast, heterogeneity decreased to 43% from 71% for patients with ASPECT score >6. While most efficacy and safety measures were consistent across 1- and 2-year follow-ups, the decline in quality of life at 2 years suggests that long-term factors such as recurrent strokes, aging, and post-stroke complications may attenuate the benefits of EVT. This highlights the need for long-term follow-up in future studies to better understand the durability of treatment effects. Moreover, these findings confirm the consistent benefits of EVT across patients with different infarct sizes and follow-up durations, while showing varying relative risks among specific subgroups.

The heterogeneity observed in our meta-analysis may be attributed to several factors, including differences in study populations, such as variability in patient age, stroke severity, or comorbidities, which can impact treatment outcomes. Additionally, variations in EVT techniques, including device type, procedural approach, or operator experience, may influence treatment efficacy. Additionally, differences in patient selection criteria, imaging methods, and adjunctive medical management, such as thrombolysis use, blood pressure control, and antithrombotics, can contribute to heterogeneity. Disparities in rehabilitation intensity and access across healthcare systems, procedural expertise, and post-acute care also play a role. Furthermore, inconsistencies in outcome assessment methods, handling of missing data, and regional differences may further contribute to the observed variability in results across trials. The duration of follow-up also plays a role, as longer follow-up periods may reveal more pronounced treatment effects, while differences in outcome assessment tools or methods can further contribute to heterogeneity. By understanding these potential sources of heterogeneity, we can better interpret our findings and highlight areas for future research, such as standardizing EVT techniques and outcome assessment methods to minimize variability and provide more robust evidence.

Despite the demonstrated long-term benefits of EVT, widespread clinical adoption faces several practical challenges. Integration with electronic health records (EHR) and picture archiving and communication systems (PACS) is critical for timely imaging review and decision-making, yet interoperability issues between institutions can delay treatment initiation – particularly in extended time windows where advanced imaging (e.g., CT perfusion, CTA collaterals) guides patient selection. Regulatory hurdles also pose barriers, especially when introducing new thrombectomy devices or expanding EVT use in broader patient populations (e.g., large core infarcts or older patients), which may require updated national guidelines, reimbursement models, and approvals. Clinician training and resource availability remain uneven, particularly in low-resource settings or non-comprehensive stroke centers. EVT requires specialized neurointerventional expertise and 24/7 team readiness, which is not universally available. These factors contribute to variability in patient access and treatment quality and must be addressed alongside clinical evidence to realize EVT’s full potential in practice.

This systematic review and meta-analysis aimed to comprehensively evaluate the outcomes of EVT beyond 90 days in ischemic stroke patients with a diverse range of infarct sizes and extended follow-up periods. The inclusion of five recently published extended phase trials in 2024 enhances the robustness of our findings, making it the most up-to-date evidence on this topic.

Heterogeneity and limitations

This meta-analysis has some limitations, including variability in patient populations, infarct sizes, and follow-up durations across studies. Despite performing subgroup analyses to account for these variables, the inherent characteristics of the included studies may affect the generalizability of our results. Additionally, due to limited data, the meta-analysis did not account for potential confounding factors, such as variations in post-EVT care, rehabilitation protocols, and patient adherence to medical therapy. Specifically, differences in rehabilitation intensity and duration, medication adherence, and secondary prevention strategies can influence long term patient outcomes.

To address these limitations, future large-scale RCTs should include diverse patient populations – such as those with low ASPECT scores, large ischemic cores, and varying baseline conditions – and should also control for or report key post-EVT factors including rehabilitation protocols, medication adherence, follow-up care, and lifestyle modifications, to generate more robust and generalizable findings that inform best practices for long-term stroke management. Ongoing trials, such as IN-EXTREMIS, extended LASTE, and TESLA, are expected to provide critical insights into optimal treatment windows and imaging criteria for endovascular therapy, potentially yielding conclusive evidence for its broader application.

Conclusion

This systematic review and meta-analysis showed that EVT combined with BMT in ischemic stroke patients was associated with improvements in functional outcomes (mRS score ≤2, ≤3, 4–6), quality of life, as well as reduced all-cause mortality beyond 90 days. These benefits, extending up to 24 months, were consistent across different infarct sizes, showing efficacy in both large and mild-to-moderate ischemic infarcts. Our findings reinforce EVT plus BMT as a key treatment in acute ischemic stroke with large vessel occlusion, with lasting effects beyond the conventional 90-day follow-up period.

Ethical approval

Not applicable since data for this review are taken from publicly available databases.

Consent

Informed consent was not required for this systematic review. No patients/volunteers directly involved.

Source of funding

No funding received.

Author contributions

S.S.: conceptualization, methodology, data collection, formal analysis, writing manuscript, and editing manuscript; M.O.: conceptualization, methodology, data collection, formal analysis, and supervision; M.I.: conceptualization, methodology, data collection, and formal analysis; M.A.A.: conceptualization, methodology, data collection, and formal analysis; S.A.Q., M.S.B.F., and P.K.T.: conceptualization, methodology, data collection, formal analysis; Z.H.: conceptualization, methodology, resources, writing manuscript, editing manuscript, visualization, and supervision; and A.A.D.: conceptualization, methodology, data collection, resources, writing manuscript, editing manuscript, visualization, and supervision.

Conflicts of interest disclosure

The authors have no conflicts of interest to declare.

Guarantor

Sufyan Shahid and Pawan Kumar Thada.

Research registration unique identifying number (UIN)

PROSPERO: CRD42024580763.

Provenance and peer review

No dataset were generated.

Data availability

No datasets were generated during this analysis as all the data used were publicly available.

Financial support and sponsorship

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.