Safety and efficacy of the Woven Endo-Bridge-17 device for intracranial aneurysm treatment: A systematic review and meta-analysis

Abstract

Background

The Woven Endo-Bridge (WEB) device revolutionized the treatment of wide-necked bifurcation aneurysms by intrasaccular flow diversion. The latest advancement is the WEB-17 system, offering greater flexibility with fewer wires, enabling treatment of smaller distal aneurysms using smaller microcatheters than the WEB-21 system.

Methods

We conducted a systematic review following preferred reporting items for systematic reviews and meta-analyses guidelines, analyzing data from seven retrospective cohort studies involving 483 aneurysms treated with the WEB-17 device. Statistical analysis computed pooled prevalence rates and 95% confidence intervals using appropriate models for each outcome and R software version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Technical success was achieved in 475 out of 483 aneurysms treated with the WEB-17 device, with a success rate of 98.34% (95% confidence interval (CI) = 96.72–99.17). Among the successful cases, 4.97% (95% CI = 1.60–14.39) required adjunctive devices. Adequate occlusion, defined as complete occlusion or neck remnants, was observed in 94.41% (95% CI = 88.17–97.46) of cases. Periprocedural complications were infrequent, with thromboembolic complications occurring in 4.93% (95% CI = 3.29–7.30) of cases, hemorrhagic complications in 1.28% (95% CI = 0.58–2.83), and postprocedural neurologic complications in 0.99% (95% CI = 0.31–3.14). Procedure-related morbidity was observed in 1.71% (95% CI = 0.86–3.39) of cases, and there was one procedure-related mortality reported at 0.21% (95% CI = .03–1.50). Mortality unrelated to the procedure occurred in 1% (95% CI = 0.23–4.15).

Conclusion

Our findings suggest that the WEB-17 device is associated with a high rate of technical success, favorable angiographic outcomes, and a low rate of periprocedural complications. Further research, including prospective trials, is needed to confirm these findings and establish its safety and efficacy definitively.

Introduction

Endovascular intervention has emerged as is increasingly considered for managing both ruptured and unruptured intracranial aneurysms (IAs), attributed to its low complication rates, favorable functional outcomes, and diminished morbidity.^1,2 Among the diverse spectrum of IAs, wide-neck bifurcation aneurysms represent a significant subset, accounting for approximately one-third of all IAs. ¹ While endovascular techniques have proven highly effective, surgical clipping traditionally remained the preferred choice for complex aneurysms such as wide-neck bifurcation aneurysms. ¹

The advent of the Woven Endo-Bridge (WEB) device has revolutionized IA management, particularly for wide-neck aneurysms. ² This innovative device comprises a self-expanding, braided wire, intrasaccular implant that disrupts blood flow within the aneurysmal neck.^2,3 The concept of intrasaccular flow disruption using the WEB device was first reported in 2011 and received approval from the US FDA in late 2018.^2–4 Numerous studies have reported durable and stable long-term occlusion outcomes following WEB deployment. ¹ However, until now, there has been a paucity of evidence regarding the long-term efficacy and safety of the WEB device. ¹ An additional advantage of the WEB device lies in its unique mechanism of action, obviating the need for dual antiplatelet therapy. The device is deployed within the aneurysmal sac to seal the neck, inducing subsequent thrombosis by creating intrasaccular blood flow stasis, all without direct contact with the parent vessel. ⁵ While several trials have assessed the WEB device's safety and efficacy through both single and multicenter retrospective and prospective series, such as the WEB clinical assessment of intrasaccular aneurysm therapy (WEBCAST), WEBCAST-2, WEB intrasaccular therapy (WEB-IT), and the French trial (French observatory), the evaluation of the newer WEB 21 and WEB 17 systems remains limited, primarily due to the restricted number of retrospective single or multicenter series available. ⁵

The recent introduction of the low-profile WEB 17 system, specifically designed for very small aneurysms, marks a noteworthy development. The WEB 17 is available in smaller sizes, commencing at 3 mm, and offers shallower devices with a 2 mm height and sizes ranging from 3 to 5 mm. Compared to the WEB 21, the WEB 17 features fewer wires (72–108 versus 144) but maintains similar metal coverage at the neck. ⁶ Considering the relative scarcity of comprehensive studies on the WEB-17 device thus far, we have undertaken this investigation to provide pooled evidence of the early-center experiences assessing the safety and efficacy of the device.

Methods

The systematic review for our meta-analysis was conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines to perform a systematic review. A comprehensive search strategy was developed to identify relevant studies using the following search terms: “Aneurysms AND (Woven EndoBridge 17 OR WEB-17)”. The literature search was conducted in the following electronic databases: PubMed, Scopus, Web of Science, and Embase, with tailoring the syntax of each database to optimize the retrieval of relevant articles. The search was limited to articles published in English before 16 June 2023. Moreover, we conducted a thorough manual search to recover any overlooked articles.

Screening and eligibility criteria

Two independent reviewers screened the titles and abstracts of the identified articles to assess their relevance to the study objectives. Moreover, full texts were then reviewed to determine their eligibility. Only original articles that met our pre-determined PICO framework were included. Our study population and intervention were patients diagnosed with IAs and treated with the WEB-17 device. No specific comparison group was required. We extracted all safety and efficacy outcomes of WEB-17 that were reported in at least two studies. We excluded non-original studies, animal studies, case reports, case series with less than five patients, meeting abstracts, and virtual studies.

Data extraction

Two independent authors extracted data from the eligible studies using a standardized data extraction form. The extracted data included the study characteristics, patient demographics (e.g. age, sex), aneurysm characteristics (e.g. size, location), safety outcomes (e.g. complications, adverse events), and efficacy outcomes (e.g. aneurysm occlusion rates, clinical outcomes). Data supporting this study is available to the corresponding author upon a reasonable request. Finally, a senior author thoroughly reviewed the extracted data to confirm its accuracy and quality.

Risk of bias assessment

The risk of bias in included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. This tool evaluates the risk of bias across several domains, including confounding, selection of participants, classification of interventions, deviations from intended interventions, missing data, measurement of outcomes, and selection of reported results.

Data synthesis and analysis

R software version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria) was used to analyze the data. Because of the heterogeneity across the included studies, we used a random-effects model to compute the pooled prevalence (%) and their related 95% confidence intervals (CIs) using the “meta” package. Additionally, we used the generalized linear mixed models method for more stability with small studies and rare events. Using Q statistics and the I² test, heterogeneity was evaluated and found to be significant when the I² value was greater than 50% or the p-value was less than 0.05. Meta-regression and publication bias assessment could not be reliably performed due to the small number of included studies.

Results

The initial search yielded a total of 56 articles. Of them, 36 articles were identified as duplicates and excluded. The remaining 20 articles were screened for title and abstract relevance. Twelve articles were identified for full-text screening. From full-text screening, seven records met our inclusion criteria.^4,5,7–11 After a thorough manual search, we did not find any relevant articles. Finally, we had seven retrospective cohort studies included in our analysis. Details of the screening process are described in the eFigure 1 in the supplement.

Study characteristics and patient demographics

The seven included studies were retrospective cohorts. Four of them were single-armed studies (WEB-17 only),^8–11 while the remaining three had two arms (WEB-17 and other devices).^4,5,7 Pagano et al. ⁵ and König et al. ⁴ compared WEB-17 to WEB-21, while Geortz et al. ⁷ compared it to the predecessor WEB devices. A total of 616 patients with 654 aneurysms were included in our meta-analysis. Four hundred forty-eight patients with 483 aneurysms were treated with WEB-17, while 168 patients with 171 aneurysms were treated using other WEB devices. The mean age of the included patients was 55.35 years. However, one study did not report any demographic information of the patients. ⁴ All studies demonstrated female predominance in the study sample (69.2% vs 30.8%). Furthermore, the postoperative follow-up periods ranged from the immediate postoperative follow-up to 12 months (eTable 1 in the supplement).

Risk of bias assessment

Assessment of the risk of bias using the ROBINS-I tool showed that two studies have a low risk of bias,^5,9 two studies have a moderate risk of bias,^10,11 while the remaining three studies have a serious risk to be biased.^4,7,8 The risk of bias was mainly due to missing data and bias due to confounding and selection of the participants (eFigure 2 in the supplement).

Aneurysm characteristics

Of 483 aneurysms treated with the WEB-17 device, the total number of recurrent aneurysms was 14 (2.9%), and the total number of ruptured aneurysms was 86 (17.8%). The majority of the treated aneurysms were located at the middle cerebral artery (MCA) (N = 161, 33.33%), followed by the anterior communicating artery (Acom) (N = 117, 24.2%), and posterior communicating artery (Pcom) (N = 56, 11.6%). Anterior circulation aneurysms were far more than posterior circulation aneurysms; further information as regards the aneurysm locations is found in eTable 2 in the supplement).

The aneurysm features were variable, with the mean neck width ranging from 2.36 mm to 5.08 mm, the aneurysm width ranging from 3.23 mm to 5.46 mm, and the aneurysm height ranging from 4 mm to 6.58. The mean dome-to-neck (D-N) ratio was reported in three studies^5,7,10 and ranged from 1.21 to 1.46. The wide-neck aneurysms were defined as either neck width ≥4 mm or a D-N ratio ≤2. The total number of wide-neck aneurysms was 140. However, three studies did not report this variable.^4,8,9 Details of the aneurysm traits are described in eTable 3 in the supplement.

Technical success and adjunctive devices

Technical success was obtained in 475 aneurysms with a rate of 98.34% (95% CI = 96.72–99.17) of the cases, and no heterogeneity was observed (I²= 0%, p = 0.528), Figure 1. Of the 475 successful cases, 4.97% (95% CI = 1.60–14.39) required an adjunctive device. In addition, moderate heterogeneity was observed (I²= 48%, p = 0.075), Figure 2.

Figure 1.

Forest plot of technical success rates.

Figure 2.

Forest plot of adjunctive device usage rates.

Use of adjunctive devices

All the studies, except for Mihalae et al., ⁹ reported using adjunctive devices to stabilize the WEB device, preserve the parent artery, and achieve complete occlusion. Stenting and coiling were the most frequently used techniques (5.7% and 2.7%, respectively). Pagano et al. described using FDs, stenting, coiling, remodeling balloons (RMs), and combinations of FD-coils or RM-stent as adjunctive devices to WEB-17. ⁶ The frequency of adjunctive device usage is summarized in eTable 4 in the supplement.

Angiographic outcomes

We included the latest follow-up results in our analysis because of the variability in the postoperative follow-up in the included studies. The angiographic outcomes (the occlusion rates) were reported in all studies. Most of the included articles mainly reported the occlusion rates at 12 months. However, Goertz et al. assessed the occlusion rates among their patients immediately postoperatively, while Rooij et al. and König et al. evaluated them at 3 months postoperatively. Our analysis showed complete occlusion ranged from 65.48% (95% CI = 45.31–75.52) to 91.67% (95% CI = 73.00–98.97). The pooled complete occlusion was achieved in 72.54% (95% CI = 63.44–80.08). However, there was moderate heterogeneity (I²= 49%, p = 0.083), Figure 3. Moreover, adequate occlusion (complete occlusion/neck remnants) ranged from 86.90% (95% CI = 77.78–93.28) to 100% (95% CI = 85.75–100). The pooled adequate occlusion was identified in 94.41% (95% CI = 88.17–97.46) of the cases. There was no heterogeneity (I²= 0%, p = 0.528), Figure 4.

Figure 3.

Forest plot of complete occlusion rates.

Figure 4.

Forest plot of adequate occlusion rates.

Safety outcomes and mortality

In safety terms, periprocedural complications were not common. Thromboembolic complications were the most frequent, with a rate of 4.93% (95% CI = 3.29–7.30), followed by hemorrhagic complications with an occurrence of 1.28% (95% CI = 0.58–2.83), while the postprocedural neurologic complications were found to be very rare (0.99% (95% CI = 0.31–3.14)). Moreover, the procedure-related morbidity rate was 1.71% (95% CI = 0.86–3.39). Additionally, only Pagano et al. ⁵ reported a single procedure-related mortality with a rate of 0.21% (95% CI = .03–1.50), while the mortality unrelated to the procedure was higher with a rate of 1% (95% CI = 0.23–4.15). Finally, there was no heterogeneity of these reported outcomes, Figure 5.

Figure 5.

Forest plot of safety outcomes.

Recanalization and retreatment

Only three of the seven studies reported retreatment either due to recanalization or incomplete occlusion of the aneurysms at follow-up among their patients.^5,8,10 Rooij et.al. reported the recanalization in four aneurysms, however only three of them underwent retreatment at 3-month follow-up. Two of the three retreated cases required additional coiling, and one required a second WEB device implantation. ¹⁰ Maurer et al. described the retreatment of three aneurysms as well. One was retreated using stent-assisted coiling, while the other required balloon-assisted coiling. ⁸ Pagano et al. reported that none of their cases required retreatment. ⁵ The pooled recanalization rate of the three studies was 4.11% (95% CI = 1.56–10.36), with no heterogeneity among the included studies (I²= 0%, p = 0.962) (eFigure 3 in the supplement).

Procedure-related morbidity

Pagano et al. and Zimmer et al. found no procedure-related morbidities in their patients.^5,11 Overall, Ischemic stroke was the most frequently occurring procedure-related morbidity resulting in clinical deterioration in the form of mild hemiparesis or reduction of concentration and mental capacity. These procedure-related morbidities mainly resulted from either thromboembolic complications or hemorrhagic complications sub-arachnoid hemorrhage. The details of the procedure-related mortality are summarized in eTable 5 in the supplement.

Discussion

Our comprehensive systematic review and meta-analysis scrutinized angiographic outcomes, technical success rates, safety outcomes, and mortality associated with using the WEB-17 device. Our systematic review and meta-analysis of 616 patients with 654 aneurysms, of which 483 aneurysms underwent treatment with the WEB-17 device, contributes significantly to the growing body of literature exploring the impact of WEB devices on the landscape of endovascular aneurysm treatment. Our analysis reveals that technical success was achieved at a rate of 98.34%, with only 4.97% of the 475 successful cases requiring adjunctive devices for completion. Based on data pooled from studies employing previous-generation WEB devices, systematic reviews^1,2 reported adequate occlusion rates of 87.1–91.1% and a complete occlusion rate of 67.10%. In contrast, our examination of aneurysms treated with the WEB-17 device yielded a pooled adequate occlusion rate of 94.41% and a complete occlusion rate of 72.54%. The higher occlusion rates could be attributed to possible attrition bias since most of the included studies have multiple patients not reported in the last angiographic follow-up, which would be more prominent in studies with small sample sizes. ¹² Another possible explanation is the relatively small mean aneurysm length (<5 mm) compared to the studies in the literature.

Notably, periprocedural complications were infrequent, with thromboembolic complications being the most prevalent, occurring at a rate of 4.93%. Only one procedure-related death was reported. ⁵ A multicenter retrospective study conducted across three high-volume German institutions further corroborated the safety and efficacy of the WEB-17 system in treating small, broad-based aneurysms. The advantages of the WEB-17 over its predecessor versions were evident in terms of enhanced treatment feasibility and a reduced thromboembolic event rate, signifying improved safety. This study underscored the WEB-17's superior navigability and diminished complications compared to earlier iterations. ⁷

Another German retrospective study, which analyzed data from two centers, comparing the use of WEB-17 with the previous-generation WEB-21 in aneurysms with a maximum width of 3–6 mm, revealed comparable technical success rates, periprocedural complication rates, and utilization of additional devices between the two systems. Notably, the WEB-17 group exhibited a higher overall complete occlusion rate at 3 months, with a pronounced difference observed in the subgroup of unruptured MCA aneurysms, highlighting the potential superiority of the WEB-17 in specific aneurysm locations. ⁴ An additional retrospective study conducted by a French group led by Pagano et al. yielded results that aligned with the aforementioned studies, demonstrating improved efficacy at 12 months, including complete and adequate occlusion, using the WEB-17 device. ⁵

The introduction of the WEB-17 system, characterized by a construct featuring fewer platinum-cored nitinol wires compared to its predecessor, the WEB-21, has facilitated the treatment of more challenging, distally located aneurysms, spanning a range from wide-necked to smaller ones. However, this innovation has also prompted inquiries and hypotheses regarding potential differences in occlusion rates compared to previous device versions. Our systematic review and meta-analysis synthesized evidence from seven retrospective cohort studies investigating the efficacy and safety of the WEB-17 device. This comprehensive analysis encompassed various parameters, including risk of bias assessment, aneurysm characteristics, technical success, angiographic outcomes, and safety considerations. Despite its reduced number of platinum-cored nitinol wires, the WEB-17 device exhibited exceptional performance as a flow-disruptive device. Furthermore, it introduced noteworthy technical advancements, such as enhanced distal navigation facilitated by the VIA 17 microcatheter compared to the more rigid VIA 27 microcatheter, improved conformity to aneurysm shape, and enhanced microcatheter navigability.^5,8

However, it is crucial to acknowledge the limitations of the current work. All seven studies included in our analysis were retrospective in nature, carrying inherent limitations typical of retrospective studies, including potential information bias due to missing data. Additionally, the inability to do subgroup analysis based on rupture status and the heterogeneity in patient populations, follow-up durations, and reported outcomes complicate the interpretation of our results. Akin to that, the number of patients lost to angiographic follow-up, and the relatively smaller aneurysm widths could have affected the pooled occlusion rates. Furthermore, almost all studies did not comprehensively summarize the treated aneurysms’ characteristics, which is essential for properly assessing the outcomes. Prospective randomized trials with long-term follow-up are imperative to further establish the indications, safety profile, and efficacy of WEB-17 in the armamentarium of aneurysm treatment.

Conclusion

While our systematic review and meta-analysis of retrospective studies offer promising insights into the utility of the WEB 17 device for IA treatment, the absence of randomized controlled trials necessitates caution in interpreting these findings. The short follow-up in some studies and the retrospective nature of the included studies underscore the need for future well-designed prospective trials to provide more robust evidence on the long-term safety and efficacy of the WEB 17 device.