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Direct comparison of Neuroform and Enterprise stents in the treatment of wide-necked intracranial aneurysms
Clinical Radiology 69 (2014) e471ee476
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Direct comparison of Neuroform and Enterprise stents in the treatment of wide-necked intracranial aneurysms C.R. Durst a, *, P. Khan b, J. Gaughen a, J. Patrie c, R.M. Starke d, P. Conant e, K.C. Liu d, M.E. Jensen a, A.J. Evans a a
Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA Batra Hospital and Medical Research Centre, New Delhi, India c Department of Public Health Services, University of Virginia, Charlottesville, VA, USA d Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA e Department of Cardiology, University of Virginia, Charlottesville, VA, USA b
art icl e i nformat ion Article history: Received 5 May 2014 Received in revised form 10 July 2014 Accepted 25 July 2014
AIM: To compare the complications and outcomes of Neuroform and Enterprise stents in the treatment of unruptured wide-necked aneurysms. MATERIALS AND METHODS: Under the auspices of the institutional review board, a review of a prospectively collected patient log identified 130 patients who underwent elective stent-assisted coil embolization of a wide-necked aneurysm, including 53 patients treated with an Enterprise stent and 77 patients treated with a Neuroform stent. Immediate and long-term clinical and radiographic outcomes were recorded for all patients. All patient data were handled in accordance with Health Insurance Portability and Accountability Act of 1996 (HIPAA) regulations. RESULTS: The technical success rate was 94%. Overall morbidity was 15% with Enterprise stents and 3% with Neuroform stents (p ¼ 0.020). However, the type of stent used was not predictive of clinical outcomes as measured by the modified Rankin scale. In a multivariate analysis, the use of a Neuroform stent was one of the predictors of retreatment (p ¼ 0.034). CONCLUSION: Multivariate analyses identified the use of Neuroform stents as an independent predictor of the need for retreatment and the use of Enterprise stents as an independent predictor of morbidity. However, the type of stent was not predictive of clinical outcome as measured by the modified Rankin scale. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Self-expandable, flexible stents are a common adjunctive tool for the treatment of complex, wide-necked aneurysms.
* Guarantor and correspondent: C.R. Durst, Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA. Tel.: þ1 434 982 0428; fax: þ1 434 924 8698. E-mail address: [email protected] (C.R. Durst).
When deployed across the neck of wide-necked aneurysms, these stents reconstruct the parent artery and serve as a buttress to prevent coil herniation. The first stent dedicated to intracranial use was the Neuroform microstent (Boston Scientific/Target, Fremont, CA, USA), approved by the Food and Drug Administration (FDA) in 2001. In 2007, the Enterprise Vascular Reconstruction Device and Delivery System (Cordis Neurovascular/Johnson & Johnson, Bridgewater, NJ, USA) was approved by the FDA. Both devices provide
http://dx.doi.org/10.1016/j.crad.2014.07.015 0009-9260/Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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significant improvements over balloon-mounted stents in navigation and deployment within tortuous cerebral vasculature. Technical success rates, complications rates, and clinical outcomes have varied throughout the literature.1e18 However, interoperator variability between the studies limits the ability to evaluate the benefits of one stent over another. This study directly compares the efficacy and safety of the Neuroform and Enterprise stents at a single centre.
Materials and methods Study design Under the auspices of the Institutional Review Board, 130 consecutive patients with wide-necked aneurysms who had been electively treated via stent-assisted coil embolization between December 2002 and June 2012 were identified from the prospectively gathered patient log. Medical and radiographic records were independently reviewed by a member of the research team who did not participate in the treatment of any of the included patients. Patient demographics, details of treatments, effects of treatments, results of follow-up procedures, and complications were recorded.
Patient selection A wide-neck aneurysm was defined as a dome-to-neck ratio of <2 or a neck diameter >4 mm.19e22 Patients who presented with subarachnoid haemorrhage or with blister or dissecting aneurysms were excluded.
Interventional procedure All patients were initiated on standard dual anti-platelet therapy, consisting of 325 mg aspirin and 75 mg clopidogrel, 3e5 days prior to their procedure. Endovascular intervention was performed by one of four neurointerventionalists using a biplane flat panel digital subtraction unit under general anaesthesia. All of the patients included in this study were given a bolus of heparin at the beginning of the procedure to reach an activated clotting time (ACT) of 250e300 s. When possible, the aneurysm was accessed through the stent and coiled under roadmap guidance during the same procedure. However, in just under a third of the cases, the patient was brought back for coiling as part of a staged procedure after the stent was allowed to endothelialize. All patients were monitored in the neurological intensive care unit after the procedure. Upon discharge, all patients were to continue the dual anti-platelet regimen. Starting in October 2007, the VerifyNow system (Accumetrics, San Diego, CA, USA) was used to monitor clopidogrel and aspirin platelet-inhibition levels. Patients resistant to clopidogrel were prescribed 250 mg ticlopidine twice daily. Clopidogrel was typically prescribed for 3 months while aspirin was to be continued for life.
Outcomes Clinical and imaging outcomes were recorded for each case. Immediate treatment outcomes were documented in all cases via bi-planar digital subtraction angiography. At discharge, patients were scheduled for 6 and 12 month angiographic follow-up with intent to image via CTA, MRA, or additional angiographic studies at 24 months. The followup imaging was evaluated for stability, recurrence, retreatment, or progressive/delayed occlusion of the aneurysm. For the purposes of this study, delayed complete occlusion was defined as no residual filling of an aneurysm at follow-up after having been previously documented to have a residual. Progressive occlusion was defined as interval decrease in the size of a previously documented residual aneurysm. In cases of remnant or recurrent aneurysms, the aneurysm was classified according to the Raymond classification.23 Morbidity was defined as any haemorrhage, infarction, or dissection that was directly related to the procedure and resulted in permanent clinical sequelae. Morbidity was further divided into periprocedural morbidity, defined as those events occurring within 30 days of the procedure, and late morbidity, occurring after the first 30 days. Technical complications were divided into those causing clinical sequelae versus those that were clinically silent.
Statistical analyses Data are presented as median or mean and range for continuous variables, and as frequency and percent for categorical variables. Calculations of normality were carried out by ladder of powers and assessed graphically. Statistical analyses of categorical variables was carried out using Chisquare, Fisher’s exact test, and ManteleHaenszel test for linear association as appropriate. Statistics of means were carried out using unpaired Student’s t-test, both with and without equal variance (Levene’s test) as necessary and Wilcoxon rank sum tests when variables were not normally distributed. The following dependent variables were assessed in univariate and multivariate analysis: periprocedural complications, retreatment in patients with greater than 12 months of follow-up, aneurysm occlusion (>95%) in patients with greater than 12 months of followup, and favourable follow-up functional outcome [modified Rankin scale (mRS) 0e2]. The following patient, aneurysm, and treatment variables were assessed to determine predictors of the above dependent outcomes: gender, age, presentation, initial treatment or recurrence, mRS at presentation, aneurysm location, aneurysm vascular territory, parent artery diameter, maximal aneurysm diameter, aneurysm volume, maximum aneurysm neck diameter, dome-to-neck diameter ratio, aneurysm neck-to-parent vessel diameter ratio, volume of Cerecyte, hydrogel, and platinum coils, total coil volume, packing density, type of stent, and size of stent. Covariates predictive in univariate analysis (p < 0.20) were included in multivariable logistic regression analysis. Clinically significant variables and interaction expansion covariates were further assessed through stratification and logistic multivariable analysis as
C.R. Durst et al. / Clinical Radiology 69 (2014) e471ee476
deemed relevant. p-Values of 0.05 were considered statistically significant. All statistical analyses were performed by a biostatistician using the Stata, version 8.0 software (StataCorp LP, College Station, TX, USA).
Results
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distal tines to open (one Neuroform first-generation stent), and failure of the stent delivery system (Neuroform3). In comparison, the Enterprise stents were successfully deployed in 52 of 53 cases (98%). The single technical failure was due to an inability to navigate a tortuous vessel.
Complications
Patient demographics and aneurysm characteristics Between December 2002 and June 2012, 130 patients meeting the criteria for an unruptured wide-necked aneurysm underwent elective stent-assisted coil embolization. The average age of all patients was 56.8 years (range 20e84 years; Table 1). Eighty-one percent of the patients were female with a statistically significant difference in univariate analysis between the Enterprise and Neuroform cohorts (p ¼ 0.023). Of the 130 aneurysms in this study, 20 were included due to a neck diameter greater than 4 mm, 39 were included for a dome-to-neck ratio <2, and 71 met both criteria.
Treatment Stent-assisted coil embolization was technically successful in 122 of 130 cases (94%). In seven cases, more than one stent were required. A total of 139 stents were used in the treatment of these aneurysms. In 70 of the 77 Neuroform cases (91%), the stent was successfully deployed (eight first-generation, one Neuroform Treo, 26 Neuroform3, and 35 Neuroform EZ stents). The unsuccessful attempts were due to inability to navigate the vasculature (two Neuroform first-generation stents), migration of the stent due to user error (two Neuroform first-generation stents), premature deployment of the stent within the catheter due to user error (one Neuroform first-generation stent), failure of the
As seen in Table 2, technical complications were encountered in 16 cases (12%). Five of the 16 cases (4% overall) were clinically significant, resulting in permanent morbidity. Overall, technical complications were more common with Neuroform stents (14%) than with Enterprise stents (9%), although this was not statistically significant (p ¼ 0.588). The disparity in technical complications is due in large part to the inherent difficulty in navigating firstgeneration Neuroform stents. Deployment of firstgeneration Neuroform stents resulted in a 43% technical complication rate, whereas subsequent generations were deployed with a combined 5% technical complication rate. As a comparison, there was a 9% technical complication rate with the Enterprise stent. The rate of morbidity following stent-assisted coil embolization of a wide-necked aneurysm was 8% overall. The 15% morbidity following Enterprise stent placement was significantly higher than the 3% morbidity following Neuroform deployment (p ¼ 0.020). All eight of the morbid cases in the Enterprise cohort were due to infarctions. Two of these eight cases occurred as a result of early in-stent thrombosis within 48 h of stent deployment, whereas two additional infarctions occurred as a result of delayed instent thrombosis at 45 and 102 days. The other four cases had small infarctions in the same vascular territory as the stent after stent deployment. Three of these four patients had documented evidence that they had discontinued
Table 1 Patient demographics and aneurysm characteristics of patients treated for an unruptured wide-necked aneurysm using Enterprise and Neuroform stents. Variable
Total (n ¼ 130)
Enterprise (n ¼ 53)
Neuroform (n ¼ 77)
56.8 11.2 [20e84] 105 (81)
57 11.7 [20e77] 48 (91)
56.7 11.6 [23e84] 57 (74)
48 32 21 14 13
14 (26) 14 (26) 11 (21) 6 (11) 5 (9)
34 (44) 18 (23) 10 (13) 8 (10) 8 (10)
Patient demographics Age (mean SD) [range] Female, n (%) Presentation (five most common) Incidental, n (%) Recurrence Headache Vertigo or ataxia Visual disturbance Aneurysm characteristics (mean SD), [range] Aneurysm diameter (mm) Aneurysm neck (mm) Dome-to-neck ratio Neck-to-parent artery ratio Aneurysm territory Anterior circulation, n (%) Posterior circulation Aneurysm location (five most common) Basilar tip, n (%) Ophthalmic Posterior communicating Paraclinoid Anterior communicating
(37) (25) (16) (11) (10)
8.1 4.5 [1.8e27] 5 2 [1.8e15] 1.6 0.5 [0.4e3.1] 1.8 0.8 [0.5e6.8]
8.5 5.2 1.6 1.9
92 (71) 38 (29)
38 (72) 15 (28)
54 (70) 23 (30)
21 (16) 19 (15) 18 (14) 17 (13) 8 (6)
7 9 8 9 3
14 (18) 10 (13) 10 (13) 8 (10) 5 (7)
(13) (17) (15) (17) (6)
5 [2.6e27] 2.2 [1.9e15] 0.5 [0.7e2.5] 1 [0.6e6.8]
7.7 4.9 1.6 1.7
4.1 1.9 0.5 0.7
[1.8e19) [1.8e10] [0.4e3.1] [0.5e3.5]
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Table 2 Complication rates for Enterprise and Neuroform stents. Variable Technical complication, n (%) With clinical sequelae Without clinical sequelae Morbidity, all Infarction Haemorrhage Periprocedural morbidity Delayed morbidity Mortality In-stent stenosis (50%) Symptomatic Asymptomatic In-stent thrombosis Symptomatic Asymptomatic
Table 3 Outcomes comparison between Enterprise and Neuroform stents.
Total (n ¼ 130)
Enterprise (n ¼ 53)
Neuroform (n ¼ 77)
16 5 11 10 9 1 7 3 0 5 0 5 5 4 1
5 2 3 8 8 0 5 3 0 4 0 4 5 4 1
11 3 8 2 1 1 2 0 0 1 0 1 0 0 0
(12) (4) (9) (8) (7) (1) (5) (2) (0) (4) (0) (4) (4) (3) (1)
(9) (4) (6) (15) (15) (0) (9) (6) (0) (8) (0) (8) (9) (8) (1)
(14) (4) (10) (3) (1) (1) (3) (0) (0) (1) (0) (1) (0) (0) (0)
clopidogrel just prior to the infarction. Of the two morbid events in the Neuroform cohort, one occurred during the procedure as a result of a micro-guidewire perforation resulting in significant haemorrhage, and the other event was an infarction without in-stent stenosis or thrombosis that occurred on postoperative day 5. A univariate analysis identified Enterprise stents (p ¼ 0.020), increasing mRS at presentation (p ¼ 0.001), decreasing diameter of the parent artery (p ¼ 0.056), aneurysm volume (p ¼ 0.052), increasing size of the aneurysm neck (p ¼ 0.166), increasing neck-to-parent artery ratio (p ¼ 0.045), and increasing total coil volume (p ¼ 0.019) as predictors of a morbid event. In a multivariate analysis, Enterprise stents (OR ¼ 5.86, 95% CI: 1.02e33.58, p ¼ 0.047), and increasing pretreatment mRS (OR ¼ 3.716, 95% CI: 1.38e9.98, p ¼ 0.009) were statistically significant independent predictors of a morbid event (p < 0.001).
Clinical outcomes The average clinical follow-up time for all patients was 33 months (range 0e123 months). Eight patients were lost to follow-up. Approximately 95% of patients had a good clinical outcome (mRS 0e2) at discharge, and 90% of patients maintained a good clinical outcome through follow-up (Table 3). A univariate analysis identified increasing pretreatment mRS (p ¼ 0.003), increasing neck diameter (p ¼ 0.170), and increasing aneurysm volume (p ¼ 0.150) as predictors of worse clinical outcomes (mRS 3e6). In a multivariate analysis, only pretreatment mRS was predictive of unfavourable clinical outcomes (p ¼ 0.039).
Immediate imaging outcomes Of the 130 aneurysms, complete occlusion was achieved in 19 (15%) of all cases as seen in Table 3. Greater than 95% occlusion at the time of initial coiling was achieved in 55 cases (42%). In 51 cases (39%), only a tiny neck remnant was present after the initial treatment. A univariate analysis identified increasing aneurysm diameter (p ¼ 0.020), increasing aneurysm volume
Variable, n (%)
Total
Enterprise
Neuroform
126 (97) 4 (3)
50 (94) 3 (6)
76 (99) 1 (1)
123 (95) 7 (5)
48 (91) 5 (9)
75 (97) 2 (3)
110 (90) 12 (10)
44 (88) 6 (12)
66 (92) 6 (8)
130 19 (15) 51 (42) 51 (39) 87 (67) 30 (35) 36 (41) 18 (21) 16 (19)
53 7 (13) 24 (43) 24 (45) 38 (72) 14 (37) 18 (47) 6 (16) 5 (13)
77 12 32 27 49 16 18 10 10
Clinical outcomes Pretreatment mRS 0e2 mRS 3e6 Discharge mRS 0e2 mRS 3e6 Follow-up mRS 0e2 mRS 3e6 Imaging outcomes Immediate outcomes Complete occlusion >95% Immediate occlusion Neck remnant Follow-up >12 months Unchanged Progressive/delayed thrombosis Recurrence Retreatment
(16) (42) (35) (64) (33) (37) (22) (22)
mRS, modified Rankin scale.
(p ¼ 0.084), increasing neck diameter (p ¼ 0.008), increasing neck-to-parent artery ratio (p ¼ 0.126), increasing total coil volume (p ¼ 0.060), and increasing stent size (p ¼ 0.139) as predictors of a less than 95% obliteration of the aneurysm at the end of the procedure. In a multivariate analysis, increasing neck diameter (OR ¼ 0.76, 95% CI: 0.62e0.94, p ¼ 0.012) was a statistically significant independent predictors of a <95% obliteration of the aneurysm at the end of the procedure.
Follow-up imaging outcomes In the present study, the average imaging follow-up for all patients was 25 months (range 0e98 months). One hundred and two patients (78%) presented for a 6 month follow-up and 87 patients (67%) presented for at least a 12 month follow-up evaluation. Overall, there was no statistical difference in long-term occlusion rates between the Enterprise and Neuroform stents in patients with at least 12 months of follow-up (Table 3). In total, 57 of the 87 patients (65.5%) with at least 12 months of follow-up imaging had greater than 95% occlusion of the aneurysm on their most recent study. Four patients in the Enterprise group (7.5%) were found to have in-stent stenosis, three of which were mild (5.6%) and one of which was moderate (1.9%). Only one patient in the Neuroform cohort was found to have in-stent stenosis, which was considered moderate (1.3%). In patients with at least 12 months of follow-up imaging, recanalization and retreatment rates were slightly higher with Neuroform as compared to Enterprise (Table 3). A univariate analysis identified the Neuroform stent (p ¼ 0.126), increasing pretreatment mRS (p ¼ 0.150), increasing aneurysm diameter (p ¼ 0.074), and increasing aneurysm neck diameter (p ¼ 0.140) as predictors of retreatment. In a multivariate analysis, aneurysm volume (OR ¼ 1.00, 95% CI: 0.99e1.00, p ¼ 0.143) and the use of a Neuroform stent (OR ¼ 3.08, 95% CI: 0.86e8.28, p ¼ 0.089)
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were statistically significant independent predictors of the need for retreatment (p ¼ 0.034).
Discussion In the present study, the use of an Enterprise versus Neuroform stent was not predictive of the likelihood of technical success or immediate occlusion rates. However, in both univariate and multivariate analyses, the use of an Enterprise stent was predictive of a morbid event, whereas the use of a Neuroform stent was predictive of a need for retreatment. Historically, complication rates have been higher in patients requiring a stent.24,25 The 8% overall morbidity in the present study is well within the 2.8e21% range of morbidity reported in the literature.1,7e10,13,15,17,24 However, the complication rates in the present study were significantly higher with Enterprise stents as compared to Neuroform stents at 15% and 3%, respectively. Both a univariate (p ¼ 0.020) and multivariate analysis (p < 0.001) identified the use of an Enterprise stent as an independent predictor of a morbid event. Other studies investigating Neuroform and Enterprise stents individually have found similar rates of clinically significant thromboembolic events, 1.8e11%4e8,10 and 1.9e4%,14,17,18 respectively, although most of these studies focused on a single type of stent. In a direct comparison of complication rates between Enterprise and Neuroform stents, Kadkhodayan et al.26 and Izar et al.27 both reported increased risk of major complications with Enterprise stents. Izar et al. reported increased morbidity with Enterprise stents as compared to Neuroform at 4.2% and 1.9%, respectively. Kadkhodayan et al. found a statistically significant increased rate of complications with Enterprise as compared to Neuroform stents at 8.7% and 1.4%, respectively. The present results are similar, with a fivefold increase in morbidity with Enterprise stents. In both the present study and that of Kadkhodayan et al., thromboembolic events were significantly more common with Enterprise stents than with Neuroform stents. The open cell design of the Neuroform stent (Fig. 1b) allows it to conform to the curvature of the native vessel with good wall apposition.21,28 Conversely, the Enterprise stent (Fig. 1a) uses a closed cell design, which has been demonstrated to result in ovalization and kinking or buckling. This design can result in poor apposition to the vessel wall.21,29 In a study evaluating MR angiographic outcomes following Enterprise and Neuroform stent placement, a semilunar signal pattern along the outside of the stent signalled poor wall apposition. This finding, termed the crescent sign, was identified in only the Enterprise cohort and was correlated with ipsilateral DWI signal abnormalities.30 Narrowing and kinking are likely to alter flow dynamics whereas poor wall apposition can lead to stagnation of blood, providing an impetus for thrombus formation. Despite the correlation between morbidity and the use of an Enterprise stent, there was no statistically significant difference in post-procedural or long-term clinical outcomes between the Enterprise and Neuroform cohorts as
Figure 1 (a) The Enterprise stent (top) uses a closed cell design while the (b) Neuroform stent (bottom) uses an open cell design.
measured by the mRS. This is likely explained by the good recovery of five of the eight patients who experienced an infarction in the Enterprise cohort. In the present study, the initial occlusion rates were 15% for complete occlusion and 42% for 95% occlusion. There was no statistically significant difference in occlusion rates between the two stents. These rates of occlusion are less than that reported in the literature for aneurysms without a wide neck.31 As postulated by Piotin et al.,24 the lower rate of primary occlusion with stent assistance may be due to two main factors: a lack of manoeuvrability afforded to the microcatheter, which limits the ability to tightly pack the aneurysm with coils, and anti-thrombotic agents present at the time of coiling. In theory, not only do stents act as a buttress against coil migration, but they also serve to alter flow dynamics within the parent vessel and provide a scaffolding upon which endothelial cells may grow.1,32 Given these effects, it is reasonable to expect that aneurysms treated with stents would have a tendency to occlude progressively with time. In the present study, 47% of the Enterprise cohort and 37% of the Neuroform cohort saw continued thrombosis over time, similar to previously reported results.2,8,10,15,17,33 At 21 and 19%, the observed recanalization and retreatment rates in the present study, respectively, were on the higher end of the 8.1e20% recanalization rate cited in the literature.1,8,9,17,24,27,33,34 Although the recanalization rates are high with stented wide-necked aneurysms, they are lower than what has been observed with some series of non-stented wide-necked aneurysms.24,34 In a multivariate analysis, the use of a Neuroform stent was one of the predictors of retreatment (p ¼ 0.034). A similar result was reported in a recent study of 508 patients.35 Prior studies have shown that the open cell design of the Neuroform stent makes it more susceptible to “gator backing.”28 Although this helps the stent to better conform to the curvature of the vessel, it may also disrupt endothelialization and allow for continued blood flow into the aneurysm in a tortuous vessel. The major limitation of the present study is its retrospective, non-randomized design. The present authors were not aware of a selection bias related to the type of stent used based on any of the aneurysm characteristics. However, as
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each neuro-interventionalist was allowed to choose the type of stent used based on his/her experience and preference, there is a potential for selection bias. No statistically significant differences in technical success rates or immediate imaging outcomes were observed between the two stents. Multivariate analyses identified the use of Neuroform stents as an independent predictor of the need for retreatment and the use of Enterprise stents as an independent predictor of morbidity. However, despite the correlation between stent type and morbidity, the type of stent was not predictive of clinical outcome as measured by the mRS scale.
References 1. Biondi A, Janardhan V, Katz JM, et al. Neuroform stent-assisted coil embolization of wide-neck intracranial aneurysms: strategies in stent deployment and midterm follow-up. Neurosurgery 2007;61:460e8. discussion 468e469. 2. Fiorella D, Albuquerque FC, Han P, et al. Preliminary experience using the Neuroform stent for the treatment of cerebral aneurysms. Neurosurgery 2004;54:6e16. discussion 16e17. 3. Fiorella D, Albuquerque FC, Woo H, et al. Neuroform in-stent stenosis: incidence, natural history, and treatment strategies. Neurosurgery 2006;59:34e42. discussion 34e42. 4. Fiorella D, Albuquerque FC, Woo H, et al. Neuroform stent assisted aneurysm treatment: evolving treatment strategies, complications and results of long term follow-up. J Neurointerv Surg 2010;2:16e22. 5. Kadkhodayan Y, Somogyi CT, Cross 3rd DT, et al. Technical, angiographic and clinical outcomes of Neuroform 1, 2, 2 Treo and 3 devices in stentassisted coiling of intracranial aneurysms. J Neurointerv Surg 2012;4:368e74. 6. Lessne ML, Shah P, Alexander MJ, et al. Thromboembolic complications after Neuroform stent-assisted treatment of cerebral aneurysms: the Duke Cerebrovascular Center experience in 235 patients with 274 stents. Neurosurgery 2011;69:369e75. 7. Lylyk P, Ferrario A, Pasbon B, et al. Buenos Aires experience with the Neuroform self-expanding stent for the treatment of intracranial aneurysms. J Neurosurg 2005;102:235e41. 8. Maldonado IL, Machi P, Costalat V, et al. Neuroform stent-assisted coiling of unruptured intracranial aneurysms: short- and midterm results from a single-center experience with 68 patients. AJNR Am J Neuroradiol 2011;32:131e6. 9. Raslan AM, Oztaskin M, Thompson EM, et al. Neuroform stent-assisted embolization of incidental anterior communicating artery aneurysms: long-term clinical and angiographic follow-up. Neurosurgery 2011;69:27e37. discussion 37. 10. Tahtinen OI, Vanninen RL, Manninen HI, et al. Wide-necked intracranial aneurysms: treatment with stent-assisted coil embolization during acute (<72 hours) subarachnoid hemorrhagedexperience in 61 consecutive patients. Radiology 2009;253:199e208. 11. Higashida RT, Halbach VV, Dowd CF, et al. Initial clinical experience with a new self-expanding nitinol stent for the treatment of intracranial cerebral aneurysms: the Cordis Enterprise stent. AJNR Am Neuroradiol 2005;26:1751e6. 12. Lubicz B, Francois O, Levivier M, et al. Preliminary experience with the enterprise stent for endovascular treatment of complex intracranial aneurysms: potential advantages and limiting characteristics. Neurosurgery 2008;62:1063e9. discussion 1069e1070. 13. Lv X, Li Y, Xinjian Y, et al. Results of endovascular treatment for intracranial wide-necked saccular and dissecting aneurysms using the Enterprise stent: a single center experience. Eur J Radiol 2011. 14. Mocco J, Fargen KM, Albuquerque FC, et al. Delayed thrombosis or stenosis following enterprise-assisted stent-coiling: is it safe? Midterm results of the interstate collaboration of enterprise stent coiling. Neurosurgery 2011;69:908e13. discussion 913e904.
15. Mocco J, Snyder KV, Albuquerque FC, et al. Treatment of intracranial aneurysms with the Enterprise stent: a multicenter registry. J Neurosurg 2009;110:35e9. 16. Peluso JP, van Rooij WJ, Sluzewski M, et al. A new self-expandable nitinol stent for the treatment of wide-neck aneurysms: initial clinical experience. AJNR Am J Neuroradiol 2008;29:1405e8. 17. Weber W, Bendszus M, Kis B, et al. A new self-expanding nitinol stent (Enterprise) for the treatment of wide-necked intracranial aneurysms: initial clinical and angiographic results in 31 aneurysms. Neuroradiology 2007;49:555e61. 18. Yang PF, Liu JM, Huang QH, et al. Preliminary experience and short-term follow-up results of treatment of wide-necked or fusiform cerebral aneurysms with a self-expanding, closed-cell, retractable stent. J Clin Neurosci 2010;17:837e41. 19. Cloft HJ, Joseph GJ, Tong FC, et al. Use of three-dimensional Guglielmi detachable coils in the treatment of wide-necked cerebral aneurysms. AJNR Am J Neuroradiol 2000;21:1312e4. 20. Debrun GM, Aletich VA, Kehrli P, et al. Aneurysm geometry: an important criterion in selecting patients for Guglielmi detachable coiling. Neurol Med Chir (Tokyo) 1998;38(Suppl.):1e20. 21. Fernandez Zubillaga A, Guglielmi G, Vinuela F, et al. Endovascular occlusion of intracranial aneurysms with electrically detachable coils: correlation of aneurysm neck size and treatment results. AJNR Am J Neuroradiol 1994;15:815e20. 22. Hope JK, Byrne JV, Molyneux AJ. Factors influencing successful angiographic occlusion of aneurysms treated by coil embolization. AJNR Am J Neuroradiol 1999;20:391e9. 23. Roy D, Raymond J, Bouthillier A, et al. Endovascular treatment of ophthalmic segment aneurysms with Guglielmi detachable coils. AJNR Am J Neuroradiol 1997;18:1207e15. 24. Piotin M, Blanc R, Spelle L, et al. Stent-assisted coiling of intracranial aneurysms: clinical and angiographic results in 216 consecutive aneurysms. Stroke 2010;41:110e5. 25. Yahia AM, Gordon V, Whapham J, et al. Complications of Neuroform stent in endovascular treatment of intracranial aneurysms. Neurocrit Care 2008;8:19e30. 26. Kadkhodayan Y, Rhodes N, Blackburn S, et al. Comparison of enterprise with neuroform stent-assisted coiling of intracranial aneurysms. AJR Am J Roentgenol 2013;200:872e8. 27. Izar B, Rai A, Raghuram K, et al. Comparison of devices used for stentassisted coiling of intracranial aneurysms. PloS One 2011;6:e24875. 28. Krischek O, Miloslavski E, Fischer S, et al. A comparison of functional and physical properties of self-expanding intracranial stents [Neuroform3, Wingspan, Solitaire, Leoþ, Enterprise]. Minim Invasive Neurosurg 2011;54:21e8. 29. Heller RS, Malek AM. Parent vessel size and curvature strongly influence risk of incomplete stent apposition in enterprise intracranial aneurysm stent coiling. AJNR Am J Neuroradiol 2011;32:1714e20. 30. Heller RS, Miele WR, Do-Dai DD, et al. Crescent sign on magnetic resonance angiography revealing incomplete stent apposition: correlation with diffusion-weighted changes in stent-mediated coil embolization of aneurysms. J Neurosurg 2011;115:624e32. 31. Henkes H, Fischer S, Weber W, et al. Endovascular coil occlusion of 1811 intracranial aneurysms: early angiographic and clinical results. Neurosurgery 2004;54:268e80. discussion 280e265. 32. Bendok BR, Parkinson RJ, Hage ZA, et al. The effect of vascular reconstruction device-assisted coiling on packing density, effective neck coverage, and angiographic outcome: an in vitro study. Neurosurgery 2007;61:835e40. discussion 840e831. 33. Hwang G, Park H, Bang JS, et al. Comparison of 2-year angiographic outcomes of stent- and nonstent-assisted coil embolization in unruptured aneurysms with an unfavorable configuration for coiling. AJNR Am J Neuroradiol 2011;32:1707e10. 34. Lawson MF, Newman WC, Chi YY, et al. Stent-associated flow remodeling causes further occlusion of incompletely coiled aneurysms. Neurosurgery 2011;69:598e603. discussion 603e594. 35. Chalouhi N, Jabbour P, Singhal S, et al. Stent-assisted coiling of intracranial aneurysms: predictors of complications, recanalization, and outcome in 508 cases. Stroke 2013;44:1348e53.
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Direct comparison of Neuroform and Enterprise stents in the treatment of wide-necked intracranial aneurysms C.R. Durst a, *, P. Khan b, J. Gaughen a, J. Patrie c, R.M. Starke d, P. Conant e, K.C. Liu d, M.E. Jensen a, A.J. Evans a a
Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA Batra Hospital and Medical Research Centre, New Delhi, India c Department of Public Health Services, University of Virginia, Charlottesville, VA, USA d Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA e Department of Cardiology, University of Virginia, Charlottesville, VA, USA b
art icl e i nformat ion Article history: Received 5 May 2014 Received in revised form 10 July 2014 Accepted 25 July 2014
AIM: To compare the complications and outcomes of Neuroform and Enterprise stents in the treatment of unruptured wide-necked aneurysms. MATERIALS AND METHODS: Under the auspices of the institutional review board, a review of a prospectively collected patient log identified 130 patients who underwent elective stent-assisted coil embolization of a wide-necked aneurysm, including 53 patients treated with an Enterprise stent and 77 patients treated with a Neuroform stent. Immediate and long-term clinical and radiographic outcomes were recorded for all patients. All patient data were handled in accordance with Health Insurance Portability and Accountability Act of 1996 (HIPAA) regulations. RESULTS: The technical success rate was 94%. Overall morbidity was 15% with Enterprise stents and 3% with Neuroform stents (p ¼ 0.020). However, the type of stent used was not predictive of clinical outcomes as measured by the modified Rankin scale. In a multivariate analysis, the use of a Neuroform stent was one of the predictors of retreatment (p ¼ 0.034). CONCLUSION: Multivariate analyses identified the use of Neuroform stents as an independent predictor of the need for retreatment and the use of Enterprise stents as an independent predictor of morbidity. However, the type of stent was not predictive of clinical outcome as measured by the modified Rankin scale. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Self-expandable, flexible stents are a common adjunctive tool for the treatment of complex, wide-necked aneurysms.
* Guarantor and correspondent: C.R. Durst, Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA. Tel.: þ1 434 982 0428; fax: þ1 434 924 8698. E-mail address: [email protected] (C.R. Durst).
When deployed across the neck of wide-necked aneurysms, these stents reconstruct the parent artery and serve as a buttress to prevent coil herniation. The first stent dedicated to intracranial use was the Neuroform microstent (Boston Scientific/Target, Fremont, CA, USA), approved by the Food and Drug Administration (FDA) in 2001. In 2007, the Enterprise Vascular Reconstruction Device and Delivery System (Cordis Neurovascular/Johnson & Johnson, Bridgewater, NJ, USA) was approved by the FDA. Both devices provide
http://dx.doi.org/10.1016/j.crad.2014.07.015 0009-9260/Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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significant improvements over balloon-mounted stents in navigation and deployment within tortuous cerebral vasculature. Technical success rates, complications rates, and clinical outcomes have varied throughout the literature.1e18 However, interoperator variability between the studies limits the ability to evaluate the benefits of one stent over another. This study directly compares the efficacy and safety of the Neuroform and Enterprise stents at a single centre.
Materials and methods Study design Under the auspices of the Institutional Review Board, 130 consecutive patients with wide-necked aneurysms who had been electively treated via stent-assisted coil embolization between December 2002 and June 2012 were identified from the prospectively gathered patient log. Medical and radiographic records were independently reviewed by a member of the research team who did not participate in the treatment of any of the included patients. Patient demographics, details of treatments, effects of treatments, results of follow-up procedures, and complications were recorded.
Patient selection A wide-neck aneurysm was defined as a dome-to-neck ratio of <2 or a neck diameter >4 mm.19e22 Patients who presented with subarachnoid haemorrhage or with blister or dissecting aneurysms were excluded.
Interventional procedure All patients were initiated on standard dual anti-platelet therapy, consisting of 325 mg aspirin and 75 mg clopidogrel, 3e5 days prior to their procedure. Endovascular intervention was performed by one of four neurointerventionalists using a biplane flat panel digital subtraction unit under general anaesthesia. All of the patients included in this study were given a bolus of heparin at the beginning of the procedure to reach an activated clotting time (ACT) of 250e300 s. When possible, the aneurysm was accessed through the stent and coiled under roadmap guidance during the same procedure. However, in just under a third of the cases, the patient was brought back for coiling as part of a staged procedure after the stent was allowed to endothelialize. All patients were monitored in the neurological intensive care unit after the procedure. Upon discharge, all patients were to continue the dual anti-platelet regimen. Starting in October 2007, the VerifyNow system (Accumetrics, San Diego, CA, USA) was used to monitor clopidogrel and aspirin platelet-inhibition levels. Patients resistant to clopidogrel were prescribed 250 mg ticlopidine twice daily. Clopidogrel was typically prescribed for 3 months while aspirin was to be continued for life.
Outcomes Clinical and imaging outcomes were recorded for each case. Immediate treatment outcomes were documented in all cases via bi-planar digital subtraction angiography. At discharge, patients were scheduled for 6 and 12 month angiographic follow-up with intent to image via CTA, MRA, or additional angiographic studies at 24 months. The followup imaging was evaluated for stability, recurrence, retreatment, or progressive/delayed occlusion of the aneurysm. For the purposes of this study, delayed complete occlusion was defined as no residual filling of an aneurysm at follow-up after having been previously documented to have a residual. Progressive occlusion was defined as interval decrease in the size of a previously documented residual aneurysm. In cases of remnant or recurrent aneurysms, the aneurysm was classified according to the Raymond classification.23 Morbidity was defined as any haemorrhage, infarction, or dissection that was directly related to the procedure and resulted in permanent clinical sequelae. Morbidity was further divided into periprocedural morbidity, defined as those events occurring within 30 days of the procedure, and late morbidity, occurring after the first 30 days. Technical complications were divided into those causing clinical sequelae versus those that were clinically silent.
Statistical analyses Data are presented as median or mean and range for continuous variables, and as frequency and percent for categorical variables. Calculations of normality were carried out by ladder of powers and assessed graphically. Statistical analyses of categorical variables was carried out using Chisquare, Fisher’s exact test, and ManteleHaenszel test for linear association as appropriate. Statistics of means were carried out using unpaired Student’s t-test, both with and without equal variance (Levene’s test) as necessary and Wilcoxon rank sum tests when variables were not normally distributed. The following dependent variables were assessed in univariate and multivariate analysis: periprocedural complications, retreatment in patients with greater than 12 months of follow-up, aneurysm occlusion (>95%) in patients with greater than 12 months of followup, and favourable follow-up functional outcome [modified Rankin scale (mRS) 0e2]. The following patient, aneurysm, and treatment variables were assessed to determine predictors of the above dependent outcomes: gender, age, presentation, initial treatment or recurrence, mRS at presentation, aneurysm location, aneurysm vascular territory, parent artery diameter, maximal aneurysm diameter, aneurysm volume, maximum aneurysm neck diameter, dome-to-neck diameter ratio, aneurysm neck-to-parent vessel diameter ratio, volume of Cerecyte, hydrogel, and platinum coils, total coil volume, packing density, type of stent, and size of stent. Covariates predictive in univariate analysis (p < 0.20) were included in multivariable logistic regression analysis. Clinically significant variables and interaction expansion covariates were further assessed through stratification and logistic multivariable analysis as
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deemed relevant. p-Values of 0.05 were considered statistically significant. All statistical analyses were performed by a biostatistician using the Stata, version 8.0 software (StataCorp LP, College Station, TX, USA).
Results
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distal tines to open (one Neuroform first-generation stent), and failure of the stent delivery system (Neuroform3). In comparison, the Enterprise stents were successfully deployed in 52 of 53 cases (98%). The single technical failure was due to an inability to navigate a tortuous vessel.
Complications
Patient demographics and aneurysm characteristics Between December 2002 and June 2012, 130 patients meeting the criteria for an unruptured wide-necked aneurysm underwent elective stent-assisted coil embolization. The average age of all patients was 56.8 years (range 20e84 years; Table 1). Eighty-one percent of the patients were female with a statistically significant difference in univariate analysis between the Enterprise and Neuroform cohorts (p ¼ 0.023). Of the 130 aneurysms in this study, 20 were included due to a neck diameter greater than 4 mm, 39 were included for a dome-to-neck ratio <2, and 71 met both criteria.
Treatment Stent-assisted coil embolization was technically successful in 122 of 130 cases (94%). In seven cases, more than one stent were required. A total of 139 stents were used in the treatment of these aneurysms. In 70 of the 77 Neuroform cases (91%), the stent was successfully deployed (eight first-generation, one Neuroform Treo, 26 Neuroform3, and 35 Neuroform EZ stents). The unsuccessful attempts were due to inability to navigate the vasculature (two Neuroform first-generation stents), migration of the stent due to user error (two Neuroform first-generation stents), premature deployment of the stent within the catheter due to user error (one Neuroform first-generation stent), failure of the
As seen in Table 2, technical complications were encountered in 16 cases (12%). Five of the 16 cases (4% overall) were clinically significant, resulting in permanent morbidity. Overall, technical complications were more common with Neuroform stents (14%) than with Enterprise stents (9%), although this was not statistically significant (p ¼ 0.588). The disparity in technical complications is due in large part to the inherent difficulty in navigating firstgeneration Neuroform stents. Deployment of firstgeneration Neuroform stents resulted in a 43% technical complication rate, whereas subsequent generations were deployed with a combined 5% technical complication rate. As a comparison, there was a 9% technical complication rate with the Enterprise stent. The rate of morbidity following stent-assisted coil embolization of a wide-necked aneurysm was 8% overall. The 15% morbidity following Enterprise stent placement was significantly higher than the 3% morbidity following Neuroform deployment (p ¼ 0.020). All eight of the morbid cases in the Enterprise cohort were due to infarctions. Two of these eight cases occurred as a result of early in-stent thrombosis within 48 h of stent deployment, whereas two additional infarctions occurred as a result of delayed instent thrombosis at 45 and 102 days. The other four cases had small infarctions in the same vascular territory as the stent after stent deployment. Three of these four patients had documented evidence that they had discontinued
Table 1 Patient demographics and aneurysm characteristics of patients treated for an unruptured wide-necked aneurysm using Enterprise and Neuroform stents. Variable
Total (n ¼ 130)
Enterprise (n ¼ 53)
Neuroform (n ¼ 77)
56.8 11.2 [20e84] 105 (81)
57 11.7 [20e77] 48 (91)
56.7 11.6 [23e84] 57 (74)
48 32 21 14 13
14 (26) 14 (26) 11 (21) 6 (11) 5 (9)
34 (44) 18 (23) 10 (13) 8 (10) 8 (10)
Patient demographics Age (mean SD) [range] Female, n (%) Presentation (five most common) Incidental, n (%) Recurrence Headache Vertigo or ataxia Visual disturbance Aneurysm characteristics (mean SD), [range] Aneurysm diameter (mm) Aneurysm neck (mm) Dome-to-neck ratio Neck-to-parent artery ratio Aneurysm territory Anterior circulation, n (%) Posterior circulation Aneurysm location (five most common) Basilar tip, n (%) Ophthalmic Posterior communicating Paraclinoid Anterior communicating
(37) (25) (16) (11) (10)
8.1 4.5 [1.8e27] 5 2 [1.8e15] 1.6 0.5 [0.4e3.1] 1.8 0.8 [0.5e6.8]
8.5 5.2 1.6 1.9
92 (71) 38 (29)
38 (72) 15 (28)
54 (70) 23 (30)
21 (16) 19 (15) 18 (14) 17 (13) 8 (6)
7 9 8 9 3
14 (18) 10 (13) 10 (13) 8 (10) 5 (7)
(13) (17) (15) (17) (6)
5 [2.6e27] 2.2 [1.9e15] 0.5 [0.7e2.5] 1 [0.6e6.8]
7.7 4.9 1.6 1.7
4.1 1.9 0.5 0.7
[1.8e19) [1.8e10] [0.4e3.1] [0.5e3.5]
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Table 2 Complication rates for Enterprise and Neuroform stents. Variable Technical complication, n (%) With clinical sequelae Without clinical sequelae Morbidity, all Infarction Haemorrhage Periprocedural morbidity Delayed morbidity Mortality In-stent stenosis (50%) Symptomatic Asymptomatic In-stent thrombosis Symptomatic Asymptomatic
Table 3 Outcomes comparison between Enterprise and Neuroform stents.
Total (n ¼ 130)
Enterprise (n ¼ 53)
Neuroform (n ¼ 77)
16 5 11 10 9 1 7 3 0 5 0 5 5 4 1
5 2 3 8 8 0 5 3 0 4 0 4 5 4 1
11 3 8 2 1 1 2 0 0 1 0 1 0 0 0
(12) (4) (9) (8) (7) (1) (5) (2) (0) (4) (0) (4) (4) (3) (1)
(9) (4) (6) (15) (15) (0) (9) (6) (0) (8) (0) (8) (9) (8) (1)
(14) (4) (10) (3) (1) (1) (3) (0) (0) (1) (0) (1) (0) (0) (0)
clopidogrel just prior to the infarction. Of the two morbid events in the Neuroform cohort, one occurred during the procedure as a result of a micro-guidewire perforation resulting in significant haemorrhage, and the other event was an infarction without in-stent stenosis or thrombosis that occurred on postoperative day 5. A univariate analysis identified Enterprise stents (p ¼ 0.020), increasing mRS at presentation (p ¼ 0.001), decreasing diameter of the parent artery (p ¼ 0.056), aneurysm volume (p ¼ 0.052), increasing size of the aneurysm neck (p ¼ 0.166), increasing neck-to-parent artery ratio (p ¼ 0.045), and increasing total coil volume (p ¼ 0.019) as predictors of a morbid event. In a multivariate analysis, Enterprise stents (OR ¼ 5.86, 95% CI: 1.02e33.58, p ¼ 0.047), and increasing pretreatment mRS (OR ¼ 3.716, 95% CI: 1.38e9.98, p ¼ 0.009) were statistically significant independent predictors of a morbid event (p < 0.001).
Clinical outcomes The average clinical follow-up time for all patients was 33 months (range 0e123 months). Eight patients were lost to follow-up. Approximately 95% of patients had a good clinical outcome (mRS 0e2) at discharge, and 90% of patients maintained a good clinical outcome through follow-up (Table 3). A univariate analysis identified increasing pretreatment mRS (p ¼ 0.003), increasing neck diameter (p ¼ 0.170), and increasing aneurysm volume (p ¼ 0.150) as predictors of worse clinical outcomes (mRS 3e6). In a multivariate analysis, only pretreatment mRS was predictive of unfavourable clinical outcomes (p ¼ 0.039).
Immediate imaging outcomes Of the 130 aneurysms, complete occlusion was achieved in 19 (15%) of all cases as seen in Table 3. Greater than 95% occlusion at the time of initial coiling was achieved in 55 cases (42%). In 51 cases (39%), only a tiny neck remnant was present after the initial treatment. A univariate analysis identified increasing aneurysm diameter (p ¼ 0.020), increasing aneurysm volume
Variable, n (%)
Total
Enterprise
Neuroform
126 (97) 4 (3)
50 (94) 3 (6)
76 (99) 1 (1)
123 (95) 7 (5)
48 (91) 5 (9)
75 (97) 2 (3)
110 (90) 12 (10)
44 (88) 6 (12)
66 (92) 6 (8)
130 19 (15) 51 (42) 51 (39) 87 (67) 30 (35) 36 (41) 18 (21) 16 (19)
53 7 (13) 24 (43) 24 (45) 38 (72) 14 (37) 18 (47) 6 (16) 5 (13)
77 12 32 27 49 16 18 10 10
Clinical outcomes Pretreatment mRS 0e2 mRS 3e6 Discharge mRS 0e2 mRS 3e6 Follow-up mRS 0e2 mRS 3e6 Imaging outcomes Immediate outcomes Complete occlusion >95% Immediate occlusion Neck remnant Follow-up >12 months Unchanged Progressive/delayed thrombosis Recurrence Retreatment
(16) (42) (35) (64) (33) (37) (22) (22)
mRS, modified Rankin scale.
(p ¼ 0.084), increasing neck diameter (p ¼ 0.008), increasing neck-to-parent artery ratio (p ¼ 0.126), increasing total coil volume (p ¼ 0.060), and increasing stent size (p ¼ 0.139) as predictors of a less than 95% obliteration of the aneurysm at the end of the procedure. In a multivariate analysis, increasing neck diameter (OR ¼ 0.76, 95% CI: 0.62e0.94, p ¼ 0.012) was a statistically significant independent predictors of a <95% obliteration of the aneurysm at the end of the procedure.
Follow-up imaging outcomes In the present study, the average imaging follow-up for all patients was 25 months (range 0e98 months). One hundred and two patients (78%) presented for a 6 month follow-up and 87 patients (67%) presented for at least a 12 month follow-up evaluation. Overall, there was no statistical difference in long-term occlusion rates between the Enterprise and Neuroform stents in patients with at least 12 months of follow-up (Table 3). In total, 57 of the 87 patients (65.5%) with at least 12 months of follow-up imaging had greater than 95% occlusion of the aneurysm on their most recent study. Four patients in the Enterprise group (7.5%) were found to have in-stent stenosis, three of which were mild (5.6%) and one of which was moderate (1.9%). Only one patient in the Neuroform cohort was found to have in-stent stenosis, which was considered moderate (1.3%). In patients with at least 12 months of follow-up imaging, recanalization and retreatment rates were slightly higher with Neuroform as compared to Enterprise (Table 3). A univariate analysis identified the Neuroform stent (p ¼ 0.126), increasing pretreatment mRS (p ¼ 0.150), increasing aneurysm diameter (p ¼ 0.074), and increasing aneurysm neck diameter (p ¼ 0.140) as predictors of retreatment. In a multivariate analysis, aneurysm volume (OR ¼ 1.00, 95% CI: 0.99e1.00, p ¼ 0.143) and the use of a Neuroform stent (OR ¼ 3.08, 95% CI: 0.86e8.28, p ¼ 0.089)
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were statistically significant independent predictors of the need for retreatment (p ¼ 0.034).
Discussion In the present study, the use of an Enterprise versus Neuroform stent was not predictive of the likelihood of technical success or immediate occlusion rates. However, in both univariate and multivariate analyses, the use of an Enterprise stent was predictive of a morbid event, whereas the use of a Neuroform stent was predictive of a need for retreatment. Historically, complication rates have been higher in patients requiring a stent.24,25 The 8% overall morbidity in the present study is well within the 2.8e21% range of morbidity reported in the literature.1,7e10,13,15,17,24 However, the complication rates in the present study were significantly higher with Enterprise stents as compared to Neuroform stents at 15% and 3%, respectively. Both a univariate (p ¼ 0.020) and multivariate analysis (p < 0.001) identified the use of an Enterprise stent as an independent predictor of a morbid event. Other studies investigating Neuroform and Enterprise stents individually have found similar rates of clinically significant thromboembolic events, 1.8e11%4e8,10 and 1.9e4%,14,17,18 respectively, although most of these studies focused on a single type of stent. In a direct comparison of complication rates between Enterprise and Neuroform stents, Kadkhodayan et al.26 and Izar et al.27 both reported increased risk of major complications with Enterprise stents. Izar et al. reported increased morbidity with Enterprise stents as compared to Neuroform at 4.2% and 1.9%, respectively. Kadkhodayan et al. found a statistically significant increased rate of complications with Enterprise as compared to Neuroform stents at 8.7% and 1.4%, respectively. The present results are similar, with a fivefold increase in morbidity with Enterprise stents. In both the present study and that of Kadkhodayan et al., thromboembolic events were significantly more common with Enterprise stents than with Neuroform stents. The open cell design of the Neuroform stent (Fig. 1b) allows it to conform to the curvature of the native vessel with good wall apposition.21,28 Conversely, the Enterprise stent (Fig. 1a) uses a closed cell design, which has been demonstrated to result in ovalization and kinking or buckling. This design can result in poor apposition to the vessel wall.21,29 In a study evaluating MR angiographic outcomes following Enterprise and Neuroform stent placement, a semilunar signal pattern along the outside of the stent signalled poor wall apposition. This finding, termed the crescent sign, was identified in only the Enterprise cohort and was correlated with ipsilateral DWI signal abnormalities.30 Narrowing and kinking are likely to alter flow dynamics whereas poor wall apposition can lead to stagnation of blood, providing an impetus for thrombus formation. Despite the correlation between morbidity and the use of an Enterprise stent, there was no statistically significant difference in post-procedural or long-term clinical outcomes between the Enterprise and Neuroform cohorts as
Figure 1 (a) The Enterprise stent (top) uses a closed cell design while the (b) Neuroform stent (bottom) uses an open cell design.
measured by the mRS. This is likely explained by the good recovery of five of the eight patients who experienced an infarction in the Enterprise cohort. In the present study, the initial occlusion rates were 15% for complete occlusion and 42% for 95% occlusion. There was no statistically significant difference in occlusion rates between the two stents. These rates of occlusion are less than that reported in the literature for aneurysms without a wide neck.31 As postulated by Piotin et al.,24 the lower rate of primary occlusion with stent assistance may be due to two main factors: a lack of manoeuvrability afforded to the microcatheter, which limits the ability to tightly pack the aneurysm with coils, and anti-thrombotic agents present at the time of coiling. In theory, not only do stents act as a buttress against coil migration, but they also serve to alter flow dynamics within the parent vessel and provide a scaffolding upon which endothelial cells may grow.1,32 Given these effects, it is reasonable to expect that aneurysms treated with stents would have a tendency to occlude progressively with time. In the present study, 47% of the Enterprise cohort and 37% of the Neuroform cohort saw continued thrombosis over time, similar to previously reported results.2,8,10,15,17,33 At 21 and 19%, the observed recanalization and retreatment rates in the present study, respectively, were on the higher end of the 8.1e20% recanalization rate cited in the literature.1,8,9,17,24,27,33,34 Although the recanalization rates are high with stented wide-necked aneurysms, they are lower than what has been observed with some series of non-stented wide-necked aneurysms.24,34 In a multivariate analysis, the use of a Neuroform stent was one of the predictors of retreatment (p ¼ 0.034). A similar result was reported in a recent study of 508 patients.35 Prior studies have shown that the open cell design of the Neuroform stent makes it more susceptible to “gator backing.”28 Although this helps the stent to better conform to the curvature of the vessel, it may also disrupt endothelialization and allow for continued blood flow into the aneurysm in a tortuous vessel. The major limitation of the present study is its retrospective, non-randomized design. The present authors were not aware of a selection bias related to the type of stent used based on any of the aneurysm characteristics. However, as
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each neuro-interventionalist was allowed to choose the type of stent used based on his/her experience and preference, there is a potential for selection bias. No statistically significant differences in technical success rates or immediate imaging outcomes were observed between the two stents. Multivariate analyses identified the use of Neuroform stents as an independent predictor of the need for retreatment and the use of Enterprise stents as an independent predictor of morbidity. However, despite the correlation between stent type and morbidity, the type of stent was not predictive of clinical outcome as measured by the mRS scale.
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