Basilar artery occlusion (BAO) is a rare but life-threatening subtype of ischemic stroke, accounting for nearly 1% of all strokes and approximately 10% of posterior circulation infarctions [1]. It is associated with high mortality and poor functional outcomes, with up to 80% of patients left severely disabled or deceased if left untreated [2]. Endovascular treatment (EVT) has become the mainstay for large vessel occlusions (LVO), especially in the anterior circulation, but its role in posterior circulation strokes, including BAO, has been supported by fewer randomized trials [3].

In anterior circulation stroke management, bridging therapy—defined as intravenous thrombolysis (IVT) followed by EVT—has been considered effective in improving early reperfusion and clinical outcomes [4]. The proposed benefit of bridging therapy in BAO lies in IVT’s potential to lyse the clot before EVT or assist in removing distal emboli not accessible by mechanical means [5]. However, the clinical benefit of bridging over EVT alone remains uncertain, particularly in BAO, where evidence is mostly derived from observational studies and registry data [6].

While some studies have reported improved rates of successful recanalization and functional independence with bridging therapy, others have failed to demonstrate significant differences in outcomes. Furthermore, IVT use may increase the risk of symptomatic intracranial hemorrhage (SICH) and delay the initiation of EVT [7]. The decision to administer IVT before EVT is also influenced by time windows, contraindications, and institutional protocols, contributing to wide variations in clinical practice.

Given the potential impact on morbidity and mortality in BAO, it is imperative to evaluate whether bridging therapy confers additional benefit over EVT alone. To date, literature lacks consensus, and a comprehensive meta-analysis is needed to guide clinical decision-making. Therefore, this meta-analysis aims to compare the efficacy of EVT combined with IVT versus EVT alone in BAO patients.

This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [8] and followed the Cochrane Handbook for Systematic Reviews of Interventions [9]. The protocol of this review was registered on PROSPERO under the ID: CRD420251108752.

Two authors (A.W. and S.R.) independently performed the initial search, and the retrieved articles were imported into the EndNote software. After removing the duplicates, the remaining articles were screened for titles and abstracts. The articles that remained after the primary screening were subjected to secondary screening through a full-text review. Any disagreements were resolved through discussion with a third reviewer (M.H.W.). The detailed study selection process is depicted in the PRISMA flowchart (Fig. 1).

Eligible studies are randomized controlled trials (RCTs) or observational studies which enrolled adult patients (aged ≥ 18 years) with radiologically confirmed acute BAO and compared outcomes between EVT + IVT and EVT alone. Included studies reported at least one of the outcomes being analyzed, mortality, or symptomatic intracerebral hemorrhage (sICH). Non-comparative studies, pediatric populations, and studies without treatment-group-specific outcomes were excluded. Additionally, the lack of consensus regarding the initiation timing of EVT in BAO led to the inclusion of studies without a specified time limit.

Two authors independently (Z.U.A. and M.A.) extracted data on an Excel sheet. The baseline characteristics extracted were study ID, study design, location, sample size, age, percentage of males, median National Institutes of Health Stroke Scale (NIHSS) score, occlusion sites, etiologies, history of previous stroke, atrial fibrillation, hypercholesterolemia, hypertension, myocardial infarction (MI), diabetes and current smoking.

The endpoints extracted were functional independence, independent ambulation, successful recanalization, mortality and sICH. Functional independence is defined as a modified Rankin score (mRS) of ≤ 2, whereas independent ambulation is defined as an mRS score of ≤ 3. The successful recanalization is defined as modified treatment in cerebral ischemia (TICI) score of 2b-3.

Randomized controlled trials were assessed using the Cochrane Risk of Bias (RoB) 2.0 tool [10], whereas the observational studies were evaluated with the Newcastle-Ottawa Scale [11]. RoB 2.0 has five domains: bias from randomization, deviations from interventions, missing data, outcome measurement, and result selection. NOS judges studies based on selection, comparability, and outcome.

The initial database search yielded 1,666 records. After removing 250 duplicates, 1,416 unique records remained for preliminary screening. Title and abstract screening led to the exclusion of 1,232 records. The remaining 184 articles were then thoroughly assessed against predefined inclusion criteria. Of these, 170 were excluded, and ultimately, fourteen studies [3, 14–26] met the inclusion criteria and were incorporated into the meta-analysis. The entire selection process is illustrated in the PRISMA flow diagram (Fig. 1).

This systematic review and meta-analysis included a total of fourteen studies, encompassing 3,745 participants – 1,422 patients with EVT and IVT and 2,323 patients with EVT alone. The ages of patients ranged from 60.5 to 72 years, whereas the median NIHSS score ranged from 13 to 28. The baseline characteristics of the included studies are reported in Table 1.

The two RCTs (BASICS 2021 [3] and BAOCHE 2022 [24]), assessed using the RoB 2.0 tool, showed low risk of bias across all domains except the ATTENTION trial [23], which showed high risk of bias due to bias arising from the randomization process and measurement of outcomes. Observational studies were evaluated using NOS, with scores ranging from 6 to 9. Guo et al. (2024 [14] and Nie et al. (2022) [21] achieved full scores (9/9), indicating high quality. Most other studies demonstrated good selection and comparability, though a few had limitations in outcome assessment and follow-up. Overall, the studies were of moderate to high quality. The RoB 2.0 traffic plot and the NOS quality assessment are given in Fig. 2 and Supplementary Table 2.

BAO remains one of the most severe forms of ischemic stroke, often resulting in devastating outcomes without effective intervention. While EVT has revolutionized management for LVO, the added benefit of IVT prior to EVT—known as “bridging therapy”—for BAO continues to generate debate. Our meta-analysis of 14 studies evaluated the impact of EVT + IVT versus EVT alone across key outcomes, including functional independence (mRS ≤ 2), independent ambulation (mRS ≤ 3), successful recanalization, mortality, and sICH.

The finding of improved functional independence with EVT + IVT is consistent with the findings of Maïer et al. [25], who analyzed a multicenter cohort and found a trend toward better functional outcomes in the EVT + IVT group, suggesting potential benefit in certain populations, despite statistical insignificance in their cohort. Similarly, the BAOCHE trial by Tao et al. demonstrated a favorable shift in the mRS distribution in the EVT + IVT group, though statistical significance was not achieved for mRS ≤ 2 as a dichotomous outcome [27]. In contrast, the BASICS trial by Langezaal et al. failed to demonstrate a functional advantage with IVT pretreatment, possibly due to high crossover rates and variable selection criteria [3].

The analysis of independent ambulation further supports the potential benefit of bridging therapy. Although the observed RR of 1.10 indicates a modest improvement, it was statistically significant. This aligns with data from Ren et al., who reported that pre-treatment with IVT led to partial clot fragmentation and facilitated thrombectomy, potentially enhancing early ambulation and neurologic recovery [28]. However, Maïer et al. noted that this effect might be confounded by earlier presentation times in the EVT + IVT group [25].

In terms of successful recanalization, no significant difference was found between EVT + IVT and EVT alone in the pooled analysis. This finding is mirrored in a study by Mueller et al. [29], who showed that prior IVT did not significantly impact angiographic success rates. The BAOCHE and BASICS trials similarly found no added benefit of IVT in terms of final TICI scores [3, 24]. This lack of effect may be due to the nature of thrombi in the posterior circulation, which are often larger and more resistant to lytic therapy, or due to the rapid efficacy of modern thrombectomy techniques.

A notable and clinically meaningful finding in this meta-analysis is the significant reduction in mortality with EVT + IVT. This effect was particularly evident in observational studies. Nappini et al. reported lower mortality rates in the bridging group, suggesting that thrombolysis may contribute to microvascular reperfusion even when macrovascular recanalization is achieved through EVT [20]. Ding et al. proposed that IVT could help dissolve distal emboli and reduce infarct volume, thus lowering the risk of fatal brainstem infarction—a plausible explanation for the survival benefit observed in our analysis [30].

However, not all studies agree. Nie et al., in their 2022 retrospective study of Chinese patients with BAO, observed no significant difference in mortality between EVT + IVT and EVT alone, raising questions about patient selection and stroke pathophysiology across different populations [21]. The higher prevalence of intracranial atherosclerotic disease (ICAD) in Asian populations may reduce the effectiveness of IVT, as clots in these patients tend to be platelet-rich and less responsive to alteplase [31]. This geographic variability reinforces the need for individualized treatment strategies.

Safety concerns, particularly regarding sICH, were unfounded in this analysis. No significant difference was observed between EVT + IVT and EVT alone, aligning with the findings of large cohort studies such as those by Goyal et al. and Kaesmacher et al., which demonstrated similar bleeding risks between treatment strategies [32, 33]. In the posterior circulation, where the brainstem’s critical structures elevate the risk of catastrophic outcomes from hemorrhage, the absence of increased sICH provides reassurance for clinicians. A study by Desilles et al. provided valuable insight by showing that IVT may reduce thrombus adhesion and stiffness, thereby enhancing EVT success without significantly increasing hemorrhagic complications [34]. Moreover, while clot migration is a theoretical concern with IVT, Ren et al. showed that such events rarely led to worse outcomes and were, in some cases, associated with improved procedural efficiency [28].

Our meta-analysis supports the use of bridging IVT in appropriately selected patients undergoing EVT for BAO. Significant benefits were observed in functional outcomes and mortality without added risk of hemorrhage. These findings align with a growing body of data suggesting that IVT can complement EVT when administered judiciously. However, the neutral findings from RCTs remind us that patient selection, stroke etiology, and treatment logistics remain crucial variables. Future trials focusing on individualized treatment pathways are needed to further refine these strategies.