A systematic review and meta-analysis of Woven EndoBridge single layer for treatment of intracranial aneurysms

Abstract

Background and purpose

The Woven EndoBridge is an intrasaccular device for the treatment of intracranial aneurysms. The first generation consisted of a high-profile double-layer braid. This review aims to evaluate the outcomes of the new generation low-profile Woven EndoBridge single layer device for intracranial aneurysm treatment.

Methods

A systematic review was conducted with Medline, Embase, and Web of Science Conference Proceedings databases. The search strategy provided 589 articles, 15 articles were included.

Results

Fifteen articles were identified reporting the use of Woven EndoBridge single-layer devices in 963 aneurysms, mostly wide-necked bifurcation aneurysms. Procedural aneurysm rupture was reported in 8 of 963 patients (0.83%; 95%CI 0.39–1.66%) and thromboembolic events in 54 of 963 patients (5.61%, 95CI 4.31–7.26%). Cumulative morbidity was 2.85% (27/949, 95%CI 1.95–4.12%) and mortality 0.93% (9/963, 95%CI 0.46–1.80%). The overall rate of adequate aneurysm occlusion at last follow-up was 83.3% (613/736; 95%CI 80.4–85.8%). Retreatment was reported in 38 aneurysms in eight studies with 450 aneurysms with follow-up (38/450; 8.4%, 95CI 6.2–11.4%). In 12 studies comprising 644 aneurysms with follow-up, rebleeds occurred in three patients in three studies with mean follow-up between 3.3 and 14.4 months (0.47%, 95%CI 0.09–1.43%)

Conclusion

Woven EndoBridge single-layer is a promising new low-profile device especially for wide-neck bifurcation aneurysms, both ruptured and unruptured. No antiplatelet medication is needed which is a great advantage, especially in ruptured aneurysms. Efficacy and safety compare favorably with (stent-assisted) coiling. However, no direct comparison with other treatments is available as yet.

Introduction

Endovascular therapy has become the first-line treatment modality for intracranial aneurysms over surgical clipping.^1–3 Wide-necked aneurysms, especially those located at arterial bifurcations, are generally not suited for simple coiling. For these aneurysms, stent- or balloon-assisted techniques and flow diverters have been developed. However, these endovascular approaches are technically more challenging and are hampered by increased complications compared to simple coiling.⁴ Besides, with stents and flow diverters, longstanding double antiplatelet therapy is needed.

The Woven EndoBridge device (WEB; Sequent Medical, Aliso Viejo, CA) is developed to overcome these limitations and improve the safety of the treatment of wide-necked bifurcation aneurysms without the need for supporting stents and concomitant dual antiplatelet therapy. The WEB consists of a self-expanding, oblong or spherical braid of platinum-cored nitinol wires intended to implant inside the aneurysmal sac, and it can be electro thermally detached. After deployment, the mesh covers the neck of the aneurysm, resulting in flow disruption in the sac and thrombosis of the aneurysm.

The WEB was introduced in Europe in 2010, and in January 2019 the US Food and Drug Administration approved the device. Since its introduction in 2010, the WEB has evolved from a high-profile dual-layer (WEB-DL) to a low-profile single-layer (WEB-SL and WEB-SLS) construction.

The WEB-DL contained a second nitinol braid and was the first available WEB device for clinical use. These double-layered devices were delivered through high profile 0.027, 0.033 and 0.038-in microcatheters. From November 2013, WEB-SLS that could be delivered through 0.027-in microcatheters for WEB sizes 4–7 mm replaced WEB-DL. In February 2015, the WEB 21 system (0.021-in microcatheters for WEB sizes 4–7 mm) was introduced. The WEB 17 system (0.017-in microcatheter for WEB sizes 3–7 mm) followed in December 2016.

The constructional improvements have enormously expanded the technical application possibilities of the WEB device. While the high profile microcatheters needed for the WEB-DL could only navigate in vessels with a straight course, the WEB 21 and 17 SL and SLS navigate through tortuous vasculature. These WEBs are also suitable for small aneurysms from 2 mm. The technical improvements resulted in an expansion of the indication for the use of the WEB. Aneurysm population characteristics in earlier studies with WEB-DL (unruptured wide-neck bifurcation aneurysms) were different from those in later studies with WEB-SLS (also more distal and sidewall aneurysms, ruptured and unruptured). Recent meta-analyses of clinical use of the WEB device have included early studies with WEB-DL.^5–8 Since WEB-DL is no longer used, these reviews might not reflect current clinical practice.

In this systematic review, we aim to assess the safety and effectiveness of the current WEB-SL and SLS device for endovascular therapy of both ruptured and unruptured intracranial aneurysms.

Methods

Search strategy and article selection

We performed a systematic review of the literature to identify studies reporting on clinical experience with WEB devices for intracranial aneurysms. For inclusion, we considered single- and multicenter retrospective and prospective cohort studies reporting on safety and outcome. This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.⁹ We searched Medline, Embase, and Web of Science Conference Proceedings databases. The WEB device was introduced in 2010 and articles published before that time were excluded. For the search strategy, key researchers and trials were identified in a scoping search and included in the search strategy on WEB devices. The search strategy was made with help from a librarian (JD) and described in Supplementary Table 1. Figure 1 shows the resulting flowchart. After importing the articles into Rayyan QCRI, we removed duplicates. Two authors (SBR and WR) independently screened titles and abstracts for articles reporting on the clinical use of the WEB device for intracranial aneurysms. For full-text screening, we selected articles in English language reporting on the clinical and imaging outcomes of aneurysms treated with a WEB device. We excluded case reports, congress abstracts, commentaries, and reviews. We included studies that reported on the use of both WEB-DL and SLS if results could be stratified. With overlapping cohorts, we included only the largest and most recent cohort was included. We consulted Web of Science for additional articles, and we checked references of selected articles for possible further relevant studies. Finally, three recent studies were added.^10–12

Data extraction

The following variables, when available, were extracted from the full text of each study: study design, number of patients, number of aneurysms treated, number of ruptured aneurysms, aneurysm type, successful WEB device placement, WEB-DL, WEB-SL/S, use of additional devices, anticoagulation protocol, thrombo-embolic complications, other complications, length of follow-up, complete aneurysm occlusion, aneurysm neck remnant, adequate occlusion (complete occlusion and neck remnant), aneurysm remnant, retreatment, and rerupture.

Results

The search identified 589 articles (Figure 1). After removing duplicates and screening for title and abstract, we excluded 562 articles and reviewed the full texts of 26 articles. Subsequently, 15 studies were included in the review,^{10,13–24,11,12} with 963 aneurysms treated with WEB SL/S. Study characteristics are displayed in Supplementary Table 1.

Figure 1.

Flowchart search strategy.

Five studies reported on the results of both WEB-DL and WEB-SL/S allowing stratification of the results.^{14,17,22–24} In one study with comparative data from WEB 17 and previous WEB versions, only the WEB 17 data could be used.¹¹

Feasibility

Eleven of 15 studies reported on feasibility. Of 986 attempted aneurysm treatments with the WEB SL/S, 953 were successful (96.7%, 95%CI 95.3–97.6%).

Additional devices

Twelve studies with a total of 832 aneurysms reported the use of additional coils and/or stents in 64 cases (7.7%) with a wide range between studies from 0% (0 of 148)¹⁰ to 15.3% (15 of 98).¹⁸ The reasons to use additional devices (primary treatment or bail-out procedure) were not elucidated in the studies.

Anticoagulation

All studies reported on anticoagulation. There was a wide variation between studies and between operators. In unruptured aneurysms, mostly heparin was used either alone,²⁰ or in combination with preloaded and prolonged single or dual antiplatelet medication. In ruptured aneurysms, the anticoagulation protocol varied between heparin in the pressure bags only^16,21 and bolus heparin followed by single or dual antiplatelet medication after the procedure.

Complications

All studies described complications and adverse events associated with WEB SL/S device placement. Procedural aneurysm rupture occurred in 8 of 963 patients (0.83%; 95%CI 0.39–1.66%). Thromboembolic events associated with the procedure happened in 54 of 963 patients (5.61%, 95CI 4.31–7.26%). Cumulative morbidity was 2.85% (27/949, 95%CI 1.95–4.12%) and mortality 0.93% (9/963, 95%CI 0.46–1.80%). Rebleeds were reported in 12 studies with 644 aneurysms with follow-up. Only three patients in three studies with mean follow-up of 3.3 and 14.4 months^15,17,22 had a rebleed (0.47%, 95%CI 0.09–1.43%).

Aneurysm occlusion and retreatment at follow-up

The overall rate of adequate aneurysm occlusion (complete occlusion or neck remnant) at last reported follow-up in 13 studies reached 83.3% (613/736; 95%CI 80.4–85.8%). Eight studies reported on retreatment during follow-up. Of 450 aneurysms with follow-up, 38 were retreated (8.4%, 95CI 6.2–11.4%).

Ruptured aneurysms

Specific outcomes for ruptured aneurysms treated with WEB-SL/S were described in two retrospective studies^16,19 and one prospective cohort study.²¹ The first retrospective study¹⁶ included 33 aneurysms, 21 of which had a mean follow-up of 14 months. Of these 21 aneurysms, 15 (71.4%) were adequately occluded, and 6 (28.6%) showed a remnant. WEB-related mortality was 12% (4/33), and morbidity was 3% (1/33). In the other retrospective study,¹⁹ no morbidity and mortality occurred in 33 aneurysms in 33 patients. Six months follow-up was available in 26 aneurysms. Adequate occlusion was reported in 25/26 (96%), and one aneurysm (4%) had a remnant. The prospective cohort study²¹ comprised 100 ruptured aneurysms. Procedure-related morbidity was 3% (3/100) and mortality 1% (1/100). At three months follow-up, 71/74 aneurysms (96%) were adequately occluded and three had a remnant (4%). Two aneurysms were retreated. Of note, in the three studies reporting on ruptured aneurysms only, no rebleeds occurred during follow-up. Comparison of outcomes of ruptured versus unruptured aneurysms treated with WEB SL/S was not possible due to study heterogeneity and lack of outcome stratification in studies reporting on cohorts with both ruptured and unruptured aneurysms.

Discussion

In this review, we describe the clinical and imaging outcomes of intracranial aneurysms treated with the WEB-SL/S. We identified seven prospective studies and eight retrospective studies totaling 963 aneurysms treated with WEB-SL/S.^{10,13–24,11,12}

We specifically sought for articles reporting on results of WEB-SL/S or articles were results of WEB-DL could be stratified and excluded. The reason why we wanted to exclude the results of aneurysms treated with WEB-DL is twofold. First, the WEB-DL was the first WEB on the market and consisted of a high profile dual-layer device needing large-bore catheters up to 0.038-in for placement. The indications were limited to difficult proximal aneurysms on arterial bifurcations that could not be treated otherwise. Second, at the beginning of the use of the WEB, it was not yet clear that oversizing the device was imperative to obtain a satisfactory occlusion over time. Over the years, the WEB evolved into a single layer device with a progressive lower profile now suitable for 0.017-in catheters. This mechanical and technical progression has expanded the range of aneurysms that can be treated and procedures are technically easier with potentially lower complication rates. A recent review by Lv et al.⁸ showed that studies with a higher proportion of WEB-DL treatments had higher morbidity figures.

Although we succeeded in extracting results for WEB-SL/S only, direct comparison with previous reviews is not possible because of heterogeneity in reporting and wide confidence intervals. Adequate occlusion rate for WEB SL/S on last follow-up was 83.3% (613/736; 95%CI 80.4–85.8%) and was in the same range as in the reviews by Lv et al.⁸ (81% (95%CI 76–85%)) and Tau et al.⁷ (81% (95%CI, 73%–88%)). In a recent meta-analysis of coiling of wide-necked bifurcation aneurysms with or without stenting,²⁵ long-term adequate occlusion rate was with 71.9% remarkably lower, but confidence intervals were still overlapping. The retreatment rate of WEB SL/S treated aneurysms in the current study was 8.4% (95%CI 6.2–11.4%). This is in the same range as the 5.2% (95% CI, 1.9–8.4%) reported for (stent-assisted) coiling.²⁶

In the current study, cumulative morbidity for WEB SL/S was 2.85% (27/949, 95%CI 1.95–4.12%) and mortality 0.93% (9/963, 95%CI 0.46–1.80%). This was not different from the review by Lv et al.⁸ (morbidity 3% (95% CI, 1–4%) and mortality 2% (95% CI, 1–3%)).

An advantage of WEB treatment for wide-neck aneurysms over stent-assisted coiling is that periprocedural and prolonged dual antiplatelet therapy is not necessary. This is in particular advantageous in the setting of ruptured wide-neck aneurysms. With stent-assisted coiling and anticoagulation, complications are higher than with simple coiling with more hemorrhagic and ischemic complications and higher mortality, especially in ruptured aneurysms.^26–30 Even though anti-platelet medication is not recommended for WEB treatment, in this review anti-coagulation protocol varied widely between studies and between ruptured versus unruptured aneurysms. Most operators used periprocedural single or dual antiplatelet therapy in unruptured aneurysms as a preventive measure with the possible use of a stent as a bailout for protrusion of the WEB over the parent vessel. When no stent was used, the antiplatelet medication was mostly discontinued. In the three studies^16,19,21 reporting on ruptured aneurysms only treated with WEB SL/S, antiplatelet medication was not used. In one study,¹⁹ heparinization was used while in the other two studies^16,21 only heparin in the pressure bags for flushing was administered.

The WEB device is a promising innovative endovascular treatment device. It is originally designed for wide-neck and bifurcation aneurysms that are technically challenging for endovascular treatment. The WEB device has shown promising results in four multicenter prospective trials.^10,15,22,23 With the progressive technical improvement of the WEB with lower profiles, smaller sizes, and low-profile catheters, indications are no longer limited to wide-neck bifurcation aneurysms. Also, sidewall aneurysms and aneurysms on distal locations are now more and more treated with the WEB. Mid-term occlusion rates are in the same range as for stent-assisted coiling, and complication rates tend to be lower, especially in ruptured aneurysms since the antiplatelet medication is not needed.^26–30 The imperative use of dual antiplatelet medication with the use of stents or extra-saccular flow diverters³¹ imposes patients with ruptured aneurysms to a significant risk of rebleed and other hemorrhagic complications.

A limitation of this review is that most included studies were single- or multicenter cohort studies with self-reported data and short follow-up. However, the included studies provide the presently best available data. Long-term results remain unknown, and no direct comparison is made yet with currently available treatment alternatives such as stent-assisted coiling, flow diversion or clipping. In the future, well-designed studies are necessary to determine the real added value of treating intracranial aneurysms with a WEB device.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

SBT van Rooij https://orcid.org/0000-0001-7163-0737

J Daams https://orcid.org/0000-0002-8025-4961

WJ van Rooij https://orcid.org/0000-0001-5931-1186

Supplemental material

Supplemental material for this article is available online.