Safety of stent-assisted coiling for the treatment of wide-necked ruptured aneurysm: A systematic literature review and meta-analysis of prevalence

Abstract

Background

Stent-assisted coil embolization of ruptured wide-necked aneurysms is a controversial treatment modality due to concerns on the peri-procedural safety of anti-platelet therapy in the setting of acute subarachnoid hemorrhage. Our aim was to systematically review the literature on stent-assisted coil embolization of acutely ruptured wide-neck aneurysms to calculate the pooled prevalence of clinical outcome, thromboembolic and hemorrhagic complication rates and overall mortality.

Methods

We searched PubMed and Google Scholar for articles published between 2009 and 2019 and stratified selected articles based on risk of publication bias. Data on thromboembolic and hemorrhagic complications, clinical outcomes and mortality rates were analyzed using quality-effects model and double arcsine transformation.

Results

24 articles were included featuring a total of 1582 patients. Thromboembolic and hemorrhagic complication rates were witnessed in 9.1% [95% CI: 6.0% – 12.7%; I² = 72.8%] and 8.7% [95% CI: 5.4 – 12.6%; I² = 77.2%] of patients, respectively. 245 patients received external ventricular drains, of which 33 (13.5%) had EVD-related hemorrhages. Total complication rate was 20.8% [95% CI: 14.2 – 28.1%; I² = 87.0%]. 57% of aneurysms were completely occluded and a favorable clinical outcome was reported in 74.7% [95% CI: 66.4 – 82.2%; I² = 86.0] of patients. Overall mortality rate came at 7.8% [95% CI: 4.8 – 11.6%; I² = 76.9%].

Conclusion

Stent-assisted coiling of ruptured intracranial aneurysm is a technically feasible procedure with controlled thromboembolic complication rate but may be associated with higher hemorrhagic and total complication rates compared to coiling alone. While stent-assisted coiling of ruptured wide-necked aneurysm seems to yield a lower rate of favorable clinical outcome, overall mortality is comparable to that of endovascular coiling alone.

Introduction

Stent-assisted coil (SAC) embolization is a popular treatment for unruptured wide-necked aneurysms, defined as aneurysms with neck ≥4 mm or dome-to-neck ratio ≤2, and has demonstrated superior long-term outcomes, higher complete occlusion and lower recurrence rates compared to endovascular coiling alone or balloon-assisted coiling.^1–3 However, stent deployment, unlike endovascular coiling alone, necessitates the administration of dual anti-platelet therapy (DAPT) to avoid thromboembolic complications.⁴ This has resulted in fierce debate regarding the safety of stent-assisted coiling and administration of DAPT in the setting of acute subarachnoid hemorrhage (SAH) for the treatment for acutely ruptured wide-necked intracranial aneurysms.⁵ On one hand, aggressive anti-platelet therapy may result in more frequent and severe hemorrhagic complications, especially if further surgical intervention is needed post-stenting. On the other hand, inadequate anti-platelet therapy may increase the risk of thromboembolic complications.⁴,⁶ As a result of this controversy, the 2012 AHA/ASA guidelines for the management of aneurysmal SAH recommend stent-assisted coiling only as a last resort for the management of acutely ruptured wide-necked aneurysms.⁷ Several case series and cohorts have been published in the past decade that outline various institutions’ experience in treating acutely ruptured wide-necked aneurysms with stent-assisted coiling. The objective of this systematic review is to analyze these studies to determine the pooled prevalence of hemorrhagic and thromboembolic complications of stent-assisted coil embolization in acutely ruptured wide-necked aneurysms. The study also aims to determine if there is an increased hemorrhagic complication rate associated with extra-ventricular drain (EVD) insertion in patients that underwent stent-assisted coil embolization for acutely ruptured wide-neck aneurysm. Finally, this article will analyze and summarize the overall clinical and radiologic outcomes and mortality rate of the patients that underwent stent-assisted coil embolization for ruptured intracranial aneurysms in the acute setting.

Materials and methods

A systematic literature review was conducted in compliance with the PRISMA protocol. The literature was obtained via the PubMed and Google Scholar search engines. Keeping in mind that interventional neuroradiology is a rapidly advancing field that has witnessed several major breakthroughs and advancements in the past decade, we decided to include in our literature search articles published between 2009 and 2019 with the following inclusion terms: “ruptured”, “intracranial”, “aneurysm”, “endovascular”, “hemorrhage”, “thromboembolic”, “coil”, “wide-neck” and “stent”. Articles containing the following terms were filtered from the search: “unruptured”, “aortic”, “coronary”, “carotid”, “vertebral”, “dissecting”, “bailout”, “rescue”. The search returned 170 articles, of which 120 articles were excluded following abstract screening. Then, the remaining 50 articles underwent full-text screening, of which 24 were found most relevant to the topic being presented in this systematic review. Articles that included other endovascular techniques besides stent-assisted coiling were excluded, but a few studies that compared stent-assisted coiling with other endovascular techniques were included. 9 articles used the Glasgow Outcome Scale (GOS) and 10 articles used the modified Rankin scale (mRs) to report clinical outcomes. mRs 0 – 2 and GOS 4 – 5 were favorable outcomes while mRs 3 – 5 and GOS 0 – 2 were unfavorable outcomes. The clinical presentation was reported in the context of the Hunt & Hess score at presentation. Most authors referred to the Raymond scale for angiographic categorization of the aneurysm post-stenting, which included complete occlusion (RR 1), residual neck (RR 2), and dome filling/residual aneurysm (RR 3). All articles reported on post-operative complications, generally dividing them into thromboembolic and hemorrhagic complications and if they required additional intervention or not. In addition, all authors described the anti-platelet regiments they deployed on their cohorts, making note of the drugs used, doses given and the duration of anti-platelet therapy prescribed.

We calculated the prevalence and 95% confidence intervals of the outcomes of interest using Double Arcsine transformation⁸ to stabilize the variance and pooled them using a quality-effects model in order to perform a meta-analysis of prevalence. We chose to use this model a priori instead of the random-effects model to assign each study a different weight in the meta-analysis depending on several factors that may affect heterogeneity, such as study design, biases, etc. By doing so, we took into account that the heterogeneity in our findings was not due to sampling error alone, but also due to differences in the way each study was carried out. A score between 0 (high risk of heterogeneity) and 1 (low risk of heterogeneity) was awarded to each study based on a pre-determined criterion created by Barendregt et al.⁹ We quantified and visualized publication bias using LFK index and Doi plot¹⁰ while the I² index was used to quantify and determine the degree of between-study heterogeneity.¹¹ These calculations were performed based on the number of studies included in the meta-analysis, the number of patients in each study and the proportion of these patients with the variable of interest. I² index values < 25%, 50% and >75% were considered to be low, moderate and high heterogeneity, respectively. A Luis Furuya Kanamori (LFK) index value > 1 or < -1 confirms the presence of asymmetry and deviation to positive or negative publication bias, respectively. Statistical analysis was conducted using MetaXL, version 5.3 (EpiGear, 2019, Rotterdam, The Netherlands).⁹

Results

A total of 24 articles all published between 2009 and 2019, met the above-mentioned criteria and reported a combined total of 1582 patients that presented with ruptured wide-neck aneurysm and treated with stent-assisted coiling in the acute stage. Gender was specified in 1014 (60.8%) patients, of which 66.6% were female. All but one study were retrospective case series done from single or multi-center analyses, as enumerated in Table 1 and Figure 1 for the PRISMA flow diagram of study selection:

Table 1.

Summary of studies selected for systematic review and meta-analysis of prevalence.

Article	Nature of article	Date published	No. of participants	Quality score*
Tähtinen et al.12	Retrospective	2009	61	0.7
Taylor et al.13	Retrospective	2010	42	0.7
Gao et al.14	Retrospective	2011	232	1.0
Kung et al.15	Retrospective	2011	131	0.8
Lodi et al.16	Retrospective	2011	22	0.7
Amenta et al.17	Retrospective	2012	65	0.8
Golshani et al.18	Retrospective	2012	36	0.8
Alurkar et al.18	Retrospective	2012	42	0.8
Santillan et al.19	Retrospective	2012	20	0.6
Li et al.20	Retrospective	2013	19	0.6
Giyek et al.21	Retrospective	2013	70	0.9
Chung et al.22	Retrospective	2014	72	0.8
Bechan et al.23	Prospective	2015	45	0.9
Li et al.24	Retrospective	2015	38	0.7
Yang et al.25	Retrospective	2015	211	0.8
Cai et al.26	Retrospective	2016	65	0.8
Zhao et al.27	Retrospective	2016	23	1.0
Muto et al.28	Retrospective	2016	40	0.7
Liu et al.29	Retrospective	2016	218	0.9
Liu et al.30	Retrospective	2017	113	0.9
Ho et al.31	Retrospective	2018	29	0.8
Zuo et al.32	Retrospective	2018	133	1.0
Roh et al.33	Retrospective	2019	38	0.8
Kim et al.34	Retrospective	2019	11	0.7

*Each article was assigned a quality score to stratify them based on risk of heterogeneity, 0 being high risk and 1 being low risk.

Figure 1.

PRISMA flow diagram of the study selection.

All but six publications, comprising 1289 (81.4%) of the 1582 patients, specified the stent they used. 509 (39.5%) of the 1289 patients received a NeuroForm stent (Stryker Neurovascular, Kalamazoo, MI, USA), 482 (37.4%) of 1289 patients received Enterprise stent (Cordis Neurovascular, Miami, FL, USA), 207 of 1289 (16.1%) received Solitaire stent (Solitaire AB neurovascular remodeling device, eV3, Inc., Irvine, CA, USA), 27 of 1289 (2.1%) received LEO stent (Balt Extrusion, Montmorency, France), 5 of 1289 received Acclino stent (Acandis, Pforzheim, Germany), 4 patients received LVIS stent (MicroVention, Tustin, California) and 14 patients received balloon-expandable stent.

Clinical outcome following stent-assisted coil embolization was recorded in 1339 (84.6%) of 1582 patients using either the modified Rankin scale (mRs) or the Glasgow Outcome Scale (GOS). The mRs scale was used to assess 643 (48.0%) of the 1339 patients: A good score (mRs 0 – 2) was given to 531 (81.4%) of the 510 patients at discharge. Glasgow Outcome Scale (GOS) was used to grade the clinical status of 499 (37.2%) of the 1339 patients in this study: A good outcome (GOS 4 – 5) was given to 439 (88.0%) of the 499 patients at discharge. One article used neither mRs or GOS scales, but mentioned that 25 patients had a full recovery at discharge. Overall, 995 (74.3%) of the 1339 patients whose clinical status was recorded had favorable clinical outcomes at discharge.

Details on the nature of the post-procedural thromboembolic and hemorrhagic complications are detailed in Table 2. Non-specific thromboembolic events were the most common thromboembolic complication while intra-procedure re-rupture was the most common hemorrhagic complication. Pooled prevalence of thromboembolic and hemorrhagic complication rates was 9.1% [95% CI: 6.0% – 12.7%; I² = 72.8%] and 8.7% [95% CI: 5.4 – 12.6%; I² = 77.2%] of patients, respectively. Among the hemorrhagic complications, 61 (3.9%) patients suffered from intraprocedural re-rupture and 39 (2.5%) patients suffered from acute re-rupture. Forty-one (2.6%) patients suffered from vasospasms, bringing the total complication rate to 20.8% [95% CI: 14.2 – 28.1%; I² = 87.0%]. Favorable clinical outcome (mRs 0 – 2 or GOS 4 – 5) had a pooled prevalence of 74.7% [95% CI: 66.4 – 82.2%; I² = 86.0] of patients and overall mortality rate came at 7.8% [95% CI: 4.8 – 11.6%; I² = 76.9%] (Table 3 and Figure 2).

Table 2.

Summary of the types of thromboembolic and hemorrhagic complications reported in the selected studies and their prevalence as a percentage of the total thromboembolic and hemorrhagic complication rates.

Thromboembolic complications (N = 152)	Hemorrhagic complications (N = 148)
• Thromboembolic event: 72 (47.0%)	• Intra-procedure re-rupture: 61 (41.2%)
• In-stent thrombosis: 35 (23.0%)	• Post-procedure re-rupture: 39 (26.4%)
• Post-op ischemic event: 31 (20.4%)	• EVD-related hemorrhage: 33 (22.3%)
• Stent-unrelated thrombosis: 7 (4.6%)	• Other hemorrhagic complications: 14 (9.5%)
• Infarction: 7 (4.6%)	• Remote intra-parenchymal hemorrhage: 1 (0.7%)

Table 3.

The pooled prevalence of different outcomes of interest.

Outcome of interest	Pooled prevalence	LCI 95%	HCI 95%	I2	LFK index
Favorable clinical outcome*	0.747 (74.7%)	0.664 (66.4%)	0.822 (82.2%)	86.008	−1.14
Thromboembolic complications	0.091 (9.1%)	0.060 (6.0%)	0.127 (12.7%)	72.784	+1.62
Hemorrhagic complications	0.087 (8.7%)	0.054 (5.4%)	0.126 (12.6%)	77.162	+1.13
Total complication rate**	0.208 (20.8%)	0.142 (14.2%)	0.281 (28.1%)	87.008	+2.16
Mortality rate	0.078 (7.8%)	0.048 (4.8%)	0.116 (11.6%)	76.917	+2.33

LCI: lower limit of confidence interval; HCI: higher limit of confidence interval.

*Four (Kung et al.,¹⁵ Santillan et al.,¹⁹ Giyek et al.,²¹ Liu et al.²⁹) of the 24 included studies were excluded from this statistical analysis as they did not specify the number of patients that underwent SAC with good clinical outcomes despite reporting overwhelmingly favorable clinical outcomes. Hence, it is safe to assume that the pooled prevalence of favorable clinical outcomes is under-estimated.

**To avoid under-estimating complication rate, we included symptomatic and asymptomatic complications in this meta-analysis.

Figure 2.

Forest plots of pooled prevalence of the following outcomes of interest: (a) favorable clinical outcome, (b) thromboembolic complications, (c) hemorrhagic complications, (d) total complications and (e) mortality rates.

EVD insertion was reported in 17 of the 24 included studies comprising 970 (64.7%) of 1582 patients. 245 (28.4%) of the 970 patients received EVD, of which 33 (13.4%) patients suffered from EVD-related hemorrhage. The total mortality rate was 9.2% (135 of 1582 patients) at the time of discharge.

Details of technical success were mentioned for 459 (23.8%) of 1582 patients and angiographic occlusion data was provided for 1412 (88.2%) of the 1582 patients. Most publications, comprising 1212 patients, opted to describe the angiographic result of the embolization using the Raymond-Roy classification system: 768 patients (53.0%) had a Raymond 1 score, 272 patients (19.2%) had a Raymond 2 score and 172 patients (12.1%) had a Raymond 3 score. Six patients had no coiling and 200 patients were assessed using a classification system different than Raymond-Roy: 51 patients had complete (>99%) occlusion, 74 patients had near-complete (90 – 99%) occlusion and 75 patients had incomplete occlusion (<90%) of the aneurysm.

Angiographic follow-up was reported in all but three articles and was done after an average of 16.6 months post-stent-assisted coiling. 1073 of 1582 (67.8%) patients had angiographic follow-up and magnetic resonance follow-up was done in 20 patients, of which 802 (74.7%) patients had favorable radiologic findings (Raymond-Roy grade 1 and complete occlusion).

All studies reported on the anti-platelet and anticoagulation regimens they used on their respective cohorts. As of yet, there is no evidence-based anticoagulation protocol for stent-assisted coiling of ruptured intracranial aneurysms and all regimens given are based on studies done for coronary stenting in the setting of acute coronary syndrome.

Discussion

In this literature review, we analyzed a relatively large cohort of patients that were treated for acute subarachnoid hemorrhage due to ruptured wide-necked aneurysms using stent-assisted coiling with anti-platelet therapy. The ISAT trial established that endovascular coiling of ruptured intracranial aneurysms was associated with higher independent survival within one year, a lower risk of seizures and a lower mortality at 7-year follow-up compared to surgical clipping.³⁵ However, there is much controversy on whether these findings would be carried over if the ruptured aneurysm was wide-necked and necessitated the utilization of a stent. In addition to being considered poor surgical candidates, wide-necked aneurysms are also very challenging to treat endovascularly, with the most feared complication being coil protrusion into the parent vessel and subtotal occlusion of the aneurysm.⁴ To avoid such disastrous complications, a stent may need to be used to achieve complete occlusion, lower recurrence rate and better durability of the coiling. In fact, Brinjkijki et al. were the first to report that a fundus-to-neck ratio < 1.2 was the strongest predictor for the need for stenting, a finding that was later confirmed by Cai et al.⁴,²⁶

Theoretically, SAC of acutely ruptured wide-necked aneurysm should be associated with a high hemorrhagic complication rate because of the need to administer antiplatelet therapy in an acute setting. However, proponents of this treatment modality argue that the use of anti-platelet therapy in this setting does not necessarily increase the risk of hemorrhagic complications because the aneurysm has already been coiled and secured. Several studies have shown that the thromboembolic complication rate in coiling without stenting of intracranial aneurysm ranges from 2 – 15%,^36–38 while hemorrhagic complication rate ranged from 1 – 5%.³⁹,⁴⁰ Bodily et al. published a systematic review in 2011 on this topic that featured 339 patients with acutely ruptured wide-necked intracranial aneurysms treated with stent-assisted coil embolization and reported an 8% hemorrhagic, 6% thromboembolic and 13% total complication rates.⁴¹ Our findings demonstrate a pooled prevalence of 9.1% [95% CI: 6.0% – 12.7%; I² = 72.8%] for thromboembolic complications and 8.7% [95% CI: 5.4 – 12.6%; I² = 77.2%] for hemorrhagic complications. Pooled prevalence of total complication rate came to 20.8% [95% CI: 14.2 – 28.1%; I² = 87.0%], higher than the 5.87 – 18.9% complication rate of ruptured intracranial aneurysms treated via coiling alone reported in other studies, including ISAT.^1,41–44 Intraprocedural rupture and acute re-rupture rates came at 3.9% and 2.5%, respectively. These findings are in concordance with the previous literature, which demonstrated that intraprocedural rupture can range from 3.0 – 5.0%, while acute re-rupture complication rate can range from 1.0%–3.6%.^45–47 Overall, our findings suggest that stent-assisted coiling of acutely ruptured wide-necked aneurysms has a thromboembolic complication rate comparable to what is reported in the literature for endovascular coiling alone, but higher hemorrhagic and total complication rates. However, we cannot determine if this difference in complication rates is clinically significant and if there are other confounding variables, such as the technical complexities of this aneurysm and the aggressive use of anti-platelet therapy, that may have contributed to these findings.

Bechan et al. conducted a prospective study comparing the complication rate of stent-assisted coiling in 45 patients with ruptured and 47 patients with unruptured wide-necked aneurysms. They demonstrated that ruptured wide-necked aneurysms treated with stent-assisted coiling in the acute setting were 10x more likely to have complications than those treated with coiling alone.²³ In a similarly designed study, Liu et al. reported an 11.5% complication rate for the SAC group vs a 9.0% complication rate for the non-SAC group that were treated for ruptured wide-necked aneurysms, but also found that the SAC group had 100% complete occlusion rate at follow-up vs a 53.8% complete occlusion rate for the non-SAC group, suggesting that stent-assisted coiling is associated with more durable coiling than coiling alone despite having a higher complication rate.³⁰ We report in our review that 73.6% of the 942 patients that underwent radiologic follow-up had stable or improved radiologic findings.

Previous literature had demonstrated that EVD-related hemorrhage was one of the most prominent independent risk factors for peri-procedural complications in SAC of ruptured wide neck aneurysm, especially given the need for prolonged administration of dual antiplatelet therapy.^48,49 Bauer et al. published a meta-analysis on 2428 ventriculostomy procedures performed in various settings that showed an overall hemorrhagic complication rate of 7.0% (95% CI: 4.5–9.4%), of which 0.8% (95% CI: 0.2–1.4%) were clinically significant.⁵⁰ Cagnazzo et al. concluded that EVD placement after starting antiplatelet therapy was associated with a 25.1% incidence of hemorrhage versus 9.1% if EVD was inserted before endovascular therapy and started anti-platelets. But they also established that EVD placement before endovascular therapy increased the risk of aneurysm re-bleed by 12.4% as compared to if EVD was inserted after endovascular therapy. Another finding by Cagnazzo et al., later confirmed by Lim et al., was that performing EVD before endovascular coiling was effective at minimizing the risk of ventriculostomy-related hemorrhagic complications and was not associated with a higher risk of re-bleeding or other EVD-related complications, but anti-platelet therapy and stent placement are still independent risk factors for hemorrhagic complications.^51,52 Nonetheless, Roh et al. discovered that SAC patients only have a slightly higher, but clinically insignificant, rate of EVD-related hemorrhagic complications compared to endovascular coiling alone and that stent use is not an independent risk factor for EVD-related hemorrhage.³³ In our systematic review, 245 EVDs were inserted and resulted in 33 (13.5%) EVD-related hemorrhages compared to the 10% EVD-related hemorrhage reported by Bodily et al.⁴¹ Most articles did not specify if the EVD-related hemorrhages occurred in those who received EVD before stenting or after stenting, thus we could not determine if there was a temporal relationship between EVD-related hemorrhage and stenting. In addition, several studies did not report on EVD-related complications, so we could not determine if DAPT resulted in a significant increase in EVD-related hemorrhage. Based on the data presented in our series and data from past literature, we cannot assume that surgical procedures done to patients on dual antiplatelet therapy is associated with a significantly increased risk of hemorrhagic complications.

Pooled prevalence of favorable clinical outcome was 74.7% [95% CI: 66.4 – 82.2%; I² = 86.0]. A retrospective study by Chalouhi et al. demonstrated that 47 patients with ruptured intracranial aneurysms treated with SAC had a 51% favorable clinical outcome compared to 99% favorable outcome in stenting for unruptured intracranial aneurysms,⁵³ while Bodily et al. reported a 67% favorable outcome rate in their review.⁴¹ Thus, compared to previous literature, our findings report a higher rate of favorable clinical outcome when stenting was used in acutely ruptured wide-necked aneurysms, but still lower than when coiling alone is used for ruptured aneurysms. In addition, Chalouhi et al. and Yang et al. demonstrated that older age (>65 years), ruptured aneurysm, Hunt and Hess grade IV – V and female sex were independent risk factors for unfavorable clinical outcome when treating wide-necked aneurysm with stent-assisted coiling.^25,53 In this systematic review, most of the patients were female, the average age was 56.2 years and 257 (19.1%) patients had H&H grade IV – V, which may explain the lower cumulative rate of favorable clinical outcomes.

The pooled prevalence of mortality in our systematic review came at 7.8% [95% CI: 4.8 – 11.6%; I² = 76.9%], which was only slightly higher than the 7.0% mortality rate of coiling without stenting group in the ISAT trials, but lower than the 19% mortality rate reported by Bodily et al.^35,41 It is worth mentioning that Bodily et al.’s review featured a much smaller number of patients and was published almost ten years ago when stenting hardware, techniques and resources were less robust, which may explain the relatively high mortality rate. Studies on stent-assisted coiling of unruptured aneurysms resulted in combined morbidity-mortality rates ranging from 1.8 – 2.9%.^54–56 Chalouhi et al. reported a morbidity-mortality rate of 12.7% and Bechan et al. reported a morbidity-mortality rate of 13% in patients with acutely ruptured aneurysms treated with SAC.^23,53 Overall, our findings in this systematic review demonstrate higher mortality in stent-assisted coil embolization compared to endovascular coiling without stenting. However, the mortality rate seems to be lower when compared to previous smaller studies done on stent-assisted coiling of acutely ruptured wide-necked aneurysms.

As of yet, there are no standardized regimens for antiplatelet therapy for endovascular stenting of intracranial aneurysms, so institutions extrapolate antiplatelet regimens from studies done on coronary stenting. The authors of the articles featured in this literature review were fairly heterogenous with the timing, dosing and combination of antiplatelets that they decided on administering to their patients. Antiplatelet therapy is a known risk factor for extra- and intracranial bleeding, yet they are a necessity in stent-assisted techniques to counteract the thrombogenicity of the stent. Studies have shown that a Clopidogrel is dose-dependent and that a loading dose of 600 mg causes major anti-platelet activity within two hours, while Aspirin is not dose-dependent and a loading dose of 100 mg is enough to cause effective anti-platelet activity within one hour.^57,58 Dual antiplatelet therapy increases the risk of bleeding by 40 – 50%, while Aspirin alone increases the risk of all types of bleeding by 1.5 – 2.5%.⁵⁹ Cagnazzo et al. reported that single antiplatelet administration (clopidogrel or ASA) was associated with a 6.3% lower rate of hemorrhagic complications than dual antiplatelet (clopidogrel and ASA) in the setting of endovascular therapy.⁶⁰ The authors of the studies featured in this literature review all utilized dual antiplatelet therapy (Clopidogrel + ASA), using Tirofiban for post-op rescue only in case of thromboembolism. However, since the protocols, dosages and timeframes they used were very heterogenous, it was difficult to determine the extent to which the reported complications were related to the antiplatelet therapy.

The most significant limitation in this systematic review is the high heterogeneity of the statistical results and the presence of publication bias, which is reflected in the LFK index >1 or <-1 and the I² numbers >75. This is because the articles included in this systematic review were mostly limited case series published by different authors in different countries and in different periods of time. In addition, the data published in these studies was independently assessed by the authors themselves with focus on different variables and outcomes. Some authors omitted certain details, such as clinical outcome or reported complication rate, which may have affected the accuracy of our findings. There may be selection bias, where many cases with catastrophic outcomes were unpublished. Aside from the findings on hemorrhagic complication rate, all other findings resulted LFK index >1 or < −1, which confirms the presence of positive or negative publication bias, respectively. Our findings on favorable clinical outcomes produced an LFK index of −1.14, which means there may exist a minor negative publication bias and that the favorable clinical outcomes are actually higher than what is stated. Overall mortality rate had an LFK index 2.33, which indicates major positive publication bias and implies that overall mortality rate may actually be higher than what is being reported by these studies. The same is noted for the thromboembolic and total complication, which have a minor positive bias. Another limitation to this study is the lack of control for various confounding variables, such as clinical presentation of patients, age, gender and other comorbidities that may have influenced our findings.

Conclusion

The findings in this systematic review indicate that stent-assisted coil embolization of acutely ruptured wide-necked aneurysms appear to have thromboembolic complication rate comparable to what is reported in the literature for coil embolization alone, but higher hemorrhagic and total complication rates. It remains to be determined if this increase in hemorrhagic complications is clinically significant and carries real implications on the clinical outcome of the patient. We could not determine if EVD-related hemorrhage was significantly increased among patients that underwent stenting because several studies did not report on EVD-related complications and did not specify the time of EVD insertion. We also found that stent-assisted coil embolization does not seem to be associated with higher mortality rate when compared to endovascular coiling alone. While we do not recommend drawing any major conclusions from this study alone, we believe that stent-assisted coil embolization is a relatively safe and effective treatment modality for ruptured wide-necked aneurysms in the acute setting. We call for wider investigation of this technique in the management of such complex intracranial aneurysms, especially if they are not candidates for other treatment options. Further studies are needed with control arms, larger cohorts and less heterogeneity to obtain more accurate data on the safety and efficacy of stent-assisted coil embolization of ruptured wide-necked intracranial aneurysms in the acute setting.

Declaration of conflicting interests

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

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Ayman Bsat https://orcid.org/0000-0001-5200-6111