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The SILK flow diverter in the treatment of intracranial aneurysms
Journal of Clinical Neuroscience 21 (2014) 203–206
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Review
The SILK flow diverter in the treatment of intracranial aneurysms Santosh B. Murthy a,⇑, Shreyansh Shah a, Aditi Shastri c, Chethan P. Venkatasubba Rao a,b, Eric M. Bershad a,b, Jose I. Suarez a,b a
Department of Neurology, Baylor College of Medicine, 6501 Fannin, NB 302, Houston, TX 77030, USA Department of Vascular Neurology and Neurocritical Care, Baylor College of Medicine, Houston, TX, USA c Department of Hematology, Montefiore Medical Center, Bronx, NY, USA b
a r t i c l e
i n f o
Article history: Received 13 April 2013 Accepted 13 July 2013
Keywords: Aneurysm occlusion Endovascular treatment Intracranial aneurysms SILK flow diverter
a b s t r a c t The SILK flow diverter (SFD; Balt Extrusion, Montmorency, France) is a flow diverting stent used in the endovascular treatment of intracranial aneurysms. It works on the principle of redirecting flow away from the aneurysm sac, leading to occlusion over time. We present a systematic review on the clinical outcomes and complications of the SFD. A literature search for English language articles were conducted on PubMed, Medline and EMBASE for articles on the treatment of intracranial aneurysms with the SILK flow diverter. The inclusion criteria were n > 10, use of SFD only, data on complications and aneurysm occlusion rate (AOR). Eight studies with 285 patients and 317 intracranial aneurysms were included. The mean age was 52.7 years and nearly 80% were women. In terms of angiographic distribution, 86.8% of aneurysms were located in the anterior circulation and 13.2% in the posterior circulation. As for the aneurysm size, 37.9% were classed as small, 44.4% as large and 17.7% as giant. Ischemic complications and parent artery occlusion each occurred in 10% of patients. Aneurysm rupture rate was 3.5%, while the cumulative mortality was 4.9%. The main outcome measure, 12 month AOR, was 81.8% with complete occlusion in 216 out of 264 aneurysms. Use of flow diverters for the treatment of intracranial aneurysm with complex morphologies has gained in popularity over the last few years. Our review suggests that SFD achieves comparable AOR to its contemporary, the Pipeline Embolization Device (ev3 Endovascular, Plymouth, MN, USA) but has a higher rate of higher rate of ischemic complications, aneurysm rupture and mortality. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Endovascular treatment of intracranial aneurysms with complex morphology such as giant, wide-necked or fusiform aneurysms is challenging. Previously, the preferred option was stent assisted coiling, which is associated with a high recanalization rate. Introduction of flow diverter stents has provided a promising alternative option for the repair of such aneurysms [1,2]. By reducing flow across the aneurysm neck, flow diverters lead to aneurysm thrombosis, and by promoting neo-intimal growth they cause parent vessel reconstruction [3,4]. In 2007, the SILK flow-diverting stent (SFD; Balt Extrusion, Montmorency, France) became the first such flow diverter entering clinical use for intracranial circulation. The SILK is made of 48 braided Nitinol strands that offer a high-coverage mesh once expanded, and is available in different diameters (2–5 mm) and lengths (15–40 mm) [5]. The SFD kit includes a self-expanding stent and a reinforced catheter (Vasco 21; Balt Extrusion) for its delivery. A distinct advantage of this delivery system in contrast to other ⇑ Corresponding author. Tel.: +1 713 798 6151. E-mail address: [email protected] (S.B. Murthy). 0967-5868/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2013.07.006
stents is that it allows resheathing and repositioning, even when up to 90% of it has been deployed [5]. While it has not yet received regulatory approval in the USA for monotherapy, it is widely used as a stand-alone treatment in Europe. Initial results with the SILK stent suggested a promising rate of aneurysm occlusion, morbidity and mortality [5–8] but recent reports have highlighted a higher risk of thromboembolic complications and delayed aneurysm rupture, especially following treatment of giant aneurysms [9,10]. To the best of our knowledge there is no comprehensive article exclusively on the clinical outcomes of SFD. We present a systematic review of the published literature to evaluate aneurysm occlusion rates, mortality and procedure-related complication rates for intracranial aneurysms treated with the SFD. 2. Materials and methods 2.1. Search strategy An English language literature search was performed on PubMed, Ovid Medline, Ovid EMBASE and Web of Science, from
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January 2005 to March 2013. A combination of the following keywords was used: ‘‘intracranial aneurysms’’, ‘‘SILK flow diverter’’, and ‘‘flow diverters’’. The bibliographies of identified studies were searched for additional referenced studies, and this method was repeated until no further studies were found. The pre-specified inclusion criteria were n > 10 patients, SILK treatment without other flow diverter use (additional coiling/stent placement patients included), and studies with information on complications and mortality.
Table 2 Angiographic distribution of 293 aneurysms reported in the relevant literature
2.2. Data extraction Data were collected by one author (S.B.M) using a standardized data-extraction spreadsheet in Excel (Microsoft, Redmond, WA, USA). Data on baseline variables included demographics, number of aneurysms treated and total number of SILK devices used. Aneurysm characteristics collected included location, diameter, size and dome to neck ratio. Aneurysms were classified as small (<10 mm), large (10–25 mm) or giant (>25 mm). Procedural complications were categorized as peri-procedural or delayed complications. A complication that occurred within 7 days of the procedure was considered peri-procedural, while those occurring beyond this time frame were considered delayed. These included acute ischemic stroke, transient ischemic attack (TIA), intracranial hemorrhage (ICH), subarachnoid hemorrhage, parent artery occlusion/ stenosis, in-stent stenosis (ISS) and other complications such as mass effect and retroperitoneal hematoma. Mortality rates for individual studies were obtained, and a cumulative mortality rate was subsequently calculated. The main outcome measure was aneurysm occlusion rate (AOR) at 12 months following SILK placement. Only patients with complete aneurysm occlusion were considered.
Angiographic distribution
No. of aneurysms
%
Extradural ICA Intradural ICA Anterior cerebral artery Middle cerebral artery P Com Basilar artery Vertebral artery PICA PCA SCA Others
76 147 14 12 7 18 5 2 2 1 9
26 50 4.8 4.1 2.3 6.1 1.7 0.7 0.7 0.3 3.3
ICA = internal carotid artery, No. = number, P Com = posterior communicating artery, PCA = posterior cerebral artery, PICA = posterior inferior cerebellar artery, SCA = superior cerebellar artery.
73.8–83.4%). The mean age was 52.7 years. One study failed to mention the mean age [11]. 3.2. Aneurysm characteristics We included a total of 317 aneurysms in this review, of which nearly 87% (n = 275, 95% CI: 83–90.5%) were found in the anterior circulation and the remaining 13% (n = 42, 95% CI: 9.5–16.9%) were present in the posterior circulation. The angiographic distribution of the aneurysms is summarized in Table 2. For the sake of homogeneity of data, the internal carotid artery (ICA) aneurysms were divided into extradural and intradural segments. The extradural portion of the ICA included the petrous and cavernous segments, while the intradural portion included the paraophthalmic and supraclinoid segments. In terms of size, 44.4% of the aneurysms were classed as large (n = 130, 95% CI: 38.7–50.1%), 37.9% (n = 111, 95% CI: 32.4–43.5%) were classed as small, and 17.7% (n = 52, 95% CI: 13.3–22.1%) were giant aneurysms. The main outcome measure was the 12 month AOR. Only one study did not report the AOR at 12 months, and was excluded from the calculation of the cumulative AOR [7]. Angiographic follow-up information at 12 months was available for 264 aneurysms. The cumulative
3. Results 3.1. Patient demographics The search resulted in 109 articles of which a total of eight studies met the inclusion criteria. The patient demographics are listed in Table 1. We included 285 patients with 317 aneurysms. There were 224 female patients (78.6%, 95% confidence interval [CI]:
Table 1 Demographics and aneurysm characteristics of patients treated with SILK flow diverter (Balt Extrusion, Montmorency, France) Posterior circulation
Small aneurysms (<10 mm)
Large aneurysms (10–25 mm)
Giant aneurysms (>25 mm)
Aneurysms occluded at 12 months, n (%)
26
5
17
12
2
20/29 (69%)
77
68
9
29
30
18
59/70 (84.3)
25
23
2
5
10
10
15/19 (78.9)
58
20 (71.4) 28
21
7
3
20
5
16/20 (80%)
24
55.3
20 (83)
24
19
5
NA
NA
NA
16/23 (69.6)
19
62.1
15 (78.9) 19
16
3
2
17
0
NA
22
53
19 (86.4) 26
19
7
13
12
1
18/21 (85.7%)
76
49.1
58 (76.2) 87
83
4
42
29
16
72/82 (87.9%)
285
52.7
224 (78.6%)
275 (86.8%) 42 (13.2%)
111 (37.9%)
130 (44.4%)
52 (17.7%)
216/264 (81.8%)
Study
No. of Mean Females, pts age, years n (%)
Total Anterior aneurysms circulation
Lubicz et al. [19] Berge et al. [27] Leonardi et al. [11] Maimon et al. [5] Tahtinen et al. [6] Shankar et al. [7] Wagner et al. [28] Vellioglu et al. [8] Summary
26
48
17 (65.4) 31
65
54
51 (78)
25
NA
24 (96)
28
317
NA = not available, No. = number, pts = patients.
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12 month AOR was 81.8% (95% CI: 77.1–86.5%) with complete occlusion in 216 aneurysms. 3.3. Complications The peri-procedural and delayed complications are listed in Table 3. The peri-procedural complication rate was 12.5% (n = 36, 95% CI: 8.7–16.3%) and the delayed complication rate was 9.9% (n = 28, 95% CI: 6.4–13.4%). The overall observed mortality rate was 4.9% (n = 14, 95% CI: 2.4–7.4%). Ischemic complications occurred in a total of 29 patients, including both stroke (7.7%, 95% CI: 4.6–10.8%) and TIA (2.5%, 95% CI: –0.7–4.3%). ICH occurred in four patients (1.4%, 95% CI: 0.04–2.8%). The delayed aneurysm rupture rate was 3.5% (n = 10, 95% CI: 1.4–5.6%). ISS was observed in 17 patients (5%, 95% CI: 2.4–7.4%) and most of the patients had a stent luminal occlusion <50%. There was a total of 29 patients with parent artery occlusion/stenosis (95% CI: 6.7–13.7%). Other complications included acute hydrocephalus, mass effect and carotid-cavernous fistula formation. 4. Discussion Our systematic review on SFD included a total of 285 patients with 317 aneurysms. The main outcome measure, 12 month AOR, was 81.8%. This is comparable to the AOR seen with the other flow diverter currently in clinical use, the Pipeline Embolization Device (PED; ev3 Endovascular, Plymouth, MN, USA). Our previous systematic review on PED showed a 6 month AOR of 79.7% [12], with progressive occlusion of the aneurysm to 81–84% by the end of 12 months [13,14]. The AOR is conspicuously higher with flow diverters in comparison with alternative treatment strategies like stent-assisted coiling. Shapiro et al. reported an AOR of 61% at variable follow-up times with stent-assisted coiling [15]. Flow diverters also appear to have minimal risk of aneurysm recurrence [1], compared to 14% with stent-assisted coiling [15] and a rate of 20–33.5% with coils alone [16,17]. In the series reported by Kulcsar et al. [18] and Lubicz et al., [19] no recanalization or reduction of occlusion status occurred, while only two patients showed a reduction in the degree of aneurysm occlusion in the SILK registry group [18]. Based on these encouraging results, the use of SFD has gradually been broadened from classical indications such as wide-neck large or fusiform aneurysms to include smaller aneurysms and also aneurysms located at bifurcations [5].
On the other hand, existing literature on SILK shows an increased rate of complications compared to PED. We calculated a peri-procedural complication rate of 12.5% and a delayed complication rate of 9.9%. In a similar review on PED, the peri-procedural complication rate was 5.7%, while the delayed complication rate was 1.9%. A noteworthy observation is that mortality is almost double with SFD (5%) compared to PED (2.3%) [12]. Interestingly, in March 2010, the manufacturer of SILK issued a field safety notice following deaths in eight patients from delayed aneurysm rupture [10]. All these patients had aneurysms with a diameter ranging from 18 to 33 mm. Purported mechanisms for aneurysm rupture include insufficient flow diversion leading to a more dangerous intra-aneurysmal flow pattern, and proteolytic enzymes released by the organizing thrombus in the aneurysmal sac causing vessel wall breakdown [20]. SFD is also thought to be more thrombogenic compared to conventional stents [8], as evidenced by a 5% rate of in-stent stenosis. But it is unclear how much of this is because of a wide heterogeneity in the antiplatelet regime following the use of flow diverters. The lower radial force exerted by SFD relative to other devices [20] also increases the risk of device migration and vessel occlusion as evidenced in many studies [6,19]. Owing to these risks, the use of SFD at vessel bifurcations remains a concern [19]. To our knowledge, there are only two studies providing a head to head comparison between SFD and PED [21,22]. They showed comparable rates of procedure-related complications and clinical outcomes including mortality. At present, two major multi-center randomized clinical trials have been planned to compare coiling and flow diverters. One is the multi-center randomized trial on selective endovascular aneurysm occlusion with coils versus parent vessel reconstruction using the SILK flow diverter (MARCO POLO) [23], and the other is the endovascular treatment of intracranial aneurysm with PED versus coils with or without stents (EVIDENCE) trial [24]. Currently underway is the Complete Occlusion of Coilable Aneurysms (COCOA) study, a randomized, multi-center study comparing coiling to the PED for treating small paraclinoid aneurysms (aneurysm diameter < 10 mm and neck diameter < 4 mm) [25]. The safety endpoint is death and ipsilateral stroke, and the effectiveness endpoint is assessed with 6 month complete aneurysmal occlusion [25]. Another trial, Flow Diversion in Intracranial Aneurysm Treatment (FIAT), comparing outcomes between flow diversion and best standard treatment (conservative, coiling or stenting) is also in the recruitment phase [26].
Table 3 Complications associated with the SILK flow diverter (Balt Extrusion, Montmorency, France) Study
Stroke
TIA
ICH
Parent artery occlusion
In-stent thrombosis
Aneurysm rupture
Mortality
Peri-procedural complications
Delayed complications
Lubicz et al. [19] Berge et al. [27] Leonardi et al. [11] Maimon et al. [5] Tahtinen et al. [6] Shankar et al. [7] Wagner et al. [28] Vellioglu et al. [8] Summary
3
0
0
8
1
1
1
6
4
6 0
2 0
1 3
6 0
5 0
3 1
2 2
5 4
7 0
4
0
0
1
2
0
1
5
2
2
0
0
4
1
0
1
1
1
2
1
0
2
0
0
2
2
4
2
2
0
4
4
0
1
4
6
3
2
0
4
4
5
4
9
4
22 (7.7%)
7 (2.5%)
4 (1.4%)
29 (10.2%)
17 (4.9%)
10 (3.5%)
14 (4.9%)
36 (12.5%)
28 (9.9%)
ICH = intracerebral hemorrhage, TIA = transient ischemic attack.
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Our study has a few noteworthy limitations. Firstly, we included both prospective and retrospective studies, which could affect the quality of the data. Secondly, only English language articles were included and it is possible that some good quality studies in other languages may have been excluded. A striking feature was the inconsistencies in the duration of antiplatelet therapy, and also regarding monotherapy versus dual therapy. Outcome measures of neurological function such as the modified Rankin score were not mentioned in most studies, precluding assessment of cumulative clinical outcomes with SFD. 5. Conclusions Flow diverters have added a new dimension to the treatment of intracranial aneurysms, ranging from the small, uncomplicated ones to the large, giant, wide-necked aneurysms. The current data suggest a distinctly higher AOR in comparison to other alternative endovascular treatment strategies. The SFD, despite offering >80% AOR, has a higher incidence of complications, particularly thromboembolic events and aneurysm rupture relative to PED. Randomized prospective trials are currently underway to further evaluate the clinical outcomes with the flow diverters. Conflicts of interest/disclosure The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References [1] Szikora I, Berentei Z, Kulcsar Z, et al. Treatment of intracranial aneurysms by functional reconstruction of the parent artery: the Budapest experience with the pipeline embolization device. AJNR 2010;31:1139–47. [2] Lylyk P, Miranda C, Ceratto R, et al. Curative endovascular reconstruction of cerebral aneurysms with the pipeline embolization device: the Buenos Aires experience. Neurosurgery 2009;64:632–42 [discussion 642–633; quiz N6]. [3] Canton G, Levy DI, Lasheras JC, et al. Flow changes caused by the sequential placement of stents across the neck of sidewall cerebral aneurysms. J Neurosurg 2005;103:891–902. [4] Lopes D, Sani S. Histological postmortem study of an internal carotid artery aneurysm treated with the Neuroform stent. Neurosurgery 2005;56:E416 [discussion E416]. [5] Maimon S, Gonen L, Nossek E, et al. Treatment of intra-cranial aneurysms with the SILK flow diverter: 2 years’ experience with 28 patients at a single center. Acta Neurochir 2012;154:979–87. [6] Tahtinen OI, Manninen HI, Vanninen RL, et al. The silk flow-diverting stent in the endovascular treatment of complex intracranial aneurysms: technical aspects and midterm results in 24 consecutive patients. Neurosurgery 2012;70:617–23 [discussion 623–614]. [7] Shankar JJ, Vandorpe R, Pickett G, et al. SILK flow diverter for treatment of intracranial aneurysms: initial experience and cost analysis. J Neurointerv Surg 2013 [Epub ahead of print]. [8] Velioglu M, Kizilkilic O, Selcuk H, et al. Early and midterm results of complex cerebral aneurysms treated with Silk stent. Neuroradiology 2012;54:1355–65.
[9] Turowski B, Macht S, Kulcsar Z, et al. Early fatal hemorrhage after endovascular cerebral aneurysm treatment with a flow diverter (SILK-Stent): do we need to rethink our concepts? Neuroradiology 2011;53:37–41. [10] Largen E. Urgent field safety notice. Montmorency, France: BALT Extrusion; 2010. Available from: http://www.imb.ie/images/uploaded/documents/ SN201006_IntracranialStentSILK_V9113_140610_FSN.pdf. [11] Leonardi M, Cirillo L, Toni F, et al. Treatment of intracranial aneurysms using flow-diverting silk stents (BALT): a single centre experience. Interv Neuroradiol 2011;17:306–15. [12] Murthy SB. Venkatasubba Rao CP, Bershad E, et al. Treatment of unruptured intracranial aneurysms with pipeline embolization device: a systematic review of literature. J Clin Neurosci 2013;20:175–7. [13] Yu SC, Kwok CK, Cheng PW, et al. Intracranial aneurysms: midterm outcome of pipeline embolization device–a prospective study in 143 patients with 178 aneurysms. Radiology 2012;265:893–901. [14] O’Kelly CJ, Spears J, Chow M, et al. Canadian experience with the pipeline embolization device for repair of unruptured intracranial aneurysms. AJNR 2013;34:381–7. [15] Shapiro M, Becske T, Sahlein D, et al. Stent-supported aneurysm coiling: a literature survey of treatment and follow-up. AJNR 2012;33:159–63. [16] Campi A, Ramzi N, Molyneux AJ, et al. Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the International Subarachnoid Aneurysm Trial (ISAT). Stroke 2007;38:1538–44. [17] Piotin M, Blanc R, Spelle L, et al. Stent-assisted coiling of intracranial aneurysms: clinical and angiographic results in 216 consecutive aneurysms. Stroke 2010;41:110–5. [18] Kulcsar Z, Ernemann U, Wetzel SG, et al. High-profile flow diverter (silk) implantation in the basilar artery: efficacy in the treatment of aneurysms and the role of the perforators. Stroke 2010;41:1690–6. [19] Lubicz B, Collignon L, Raphaeli G, et al. Flow-diverter stent for the endovascular treatment of intracranial aneurysms: a prospective study in 29 patients with 34 aneurysms. Stroke 2010;41:2247–53. [20] Kulcsar Z, Houdart E, Bonafe A, et al. Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after flow-diversion treatment. AJNR 2011;32:20–5. [21] Briganti F, Napoli M, Tortora F, et al. Italian multicenter experience with flowdiverter devices for intracranial unruptured aneurysm treatment with periprocedural complications–a retrospective data analysis. Neuroradiology 2012;54:1145–52. [22] Piano M, Valvassori L, Quilici L, et al. Midterm and long-term follow-up of cerebral aneurysms treated with flow diverter devices: a single-center experience. J Neurosurg 2013;118:408–16. [23] ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29. Identifier NCT01084681, Efficacy trial of intracranial aneurysm treatment using two different endovascular techniques (Marco Polo); 2011 June. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01084681?term= Marco+Polo&rank=1. [24] Wong GK, Kwan MC, Ng RY, et al. Flow diverters for treatment of intracranial aneurysms: current status and ongoing clinical trials. J Clin Neurosci 2011;18:737–40. [25] Chestnut Medical Technologies. California: Chestnut Medical Technologies. IDE annual report. Complet Occlusion of Coilable Aneurysms (COCOA) study; 2010. Available: http://www.fda.gov/downloads/AdvisoryCommittees/.../ UCM247158.pdf. [26] ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29. Identifier NCT01349582, FLow division in intracranial aneurysm treatment (FIAT); 2011 May [cited 2012 March]. Available from: http:// www.clinicaltrials.gov/ct2/show/NCT01349582?term=FIAT&rank=1. [27] Berge J, Biondi A, Machi P, et al. Flow diverter silk stent for the treatment of intracranial aneurysms: 1-year follow-up in a multicenter study. AJNR 2012;33(6):1150–5. [28] Wagner A, Cortsen M, Hauerberg J, et al. Treatment of intracranial aneurysms. Reconstruction of the parent artery with flow-diverting (Silk) stent. Neuroradiology 2012;54(7):709–18.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Review
The SILK flow diverter in the treatment of intracranial aneurysms Santosh B. Murthy a,⇑, Shreyansh Shah a, Aditi Shastri c, Chethan P. Venkatasubba Rao a,b, Eric M. Bershad a,b, Jose I. Suarez a,b a
Department of Neurology, Baylor College of Medicine, 6501 Fannin, NB 302, Houston, TX 77030, USA Department of Vascular Neurology and Neurocritical Care, Baylor College of Medicine, Houston, TX, USA c Department of Hematology, Montefiore Medical Center, Bronx, NY, USA b
a r t i c l e
i n f o
Article history: Received 13 April 2013 Accepted 13 July 2013
Keywords: Aneurysm occlusion Endovascular treatment Intracranial aneurysms SILK flow diverter
a b s t r a c t The SILK flow diverter (SFD; Balt Extrusion, Montmorency, France) is a flow diverting stent used in the endovascular treatment of intracranial aneurysms. It works on the principle of redirecting flow away from the aneurysm sac, leading to occlusion over time. We present a systematic review on the clinical outcomes and complications of the SFD. A literature search for English language articles were conducted on PubMed, Medline and EMBASE for articles on the treatment of intracranial aneurysms with the SILK flow diverter. The inclusion criteria were n > 10, use of SFD only, data on complications and aneurysm occlusion rate (AOR). Eight studies with 285 patients and 317 intracranial aneurysms were included. The mean age was 52.7 years and nearly 80% were women. In terms of angiographic distribution, 86.8% of aneurysms were located in the anterior circulation and 13.2% in the posterior circulation. As for the aneurysm size, 37.9% were classed as small, 44.4% as large and 17.7% as giant. Ischemic complications and parent artery occlusion each occurred in 10% of patients. Aneurysm rupture rate was 3.5%, while the cumulative mortality was 4.9%. The main outcome measure, 12 month AOR, was 81.8% with complete occlusion in 216 out of 264 aneurysms. Use of flow diverters for the treatment of intracranial aneurysm with complex morphologies has gained in popularity over the last few years. Our review suggests that SFD achieves comparable AOR to its contemporary, the Pipeline Embolization Device (ev3 Endovascular, Plymouth, MN, USA) but has a higher rate of higher rate of ischemic complications, aneurysm rupture and mortality. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Endovascular treatment of intracranial aneurysms with complex morphology such as giant, wide-necked or fusiform aneurysms is challenging. Previously, the preferred option was stent assisted coiling, which is associated with a high recanalization rate. Introduction of flow diverter stents has provided a promising alternative option for the repair of such aneurysms [1,2]. By reducing flow across the aneurysm neck, flow diverters lead to aneurysm thrombosis, and by promoting neo-intimal growth they cause parent vessel reconstruction [3,4]. In 2007, the SILK flow-diverting stent (SFD; Balt Extrusion, Montmorency, France) became the first such flow diverter entering clinical use for intracranial circulation. The SILK is made of 48 braided Nitinol strands that offer a high-coverage mesh once expanded, and is available in different diameters (2–5 mm) and lengths (15–40 mm) [5]. The SFD kit includes a self-expanding stent and a reinforced catheter (Vasco 21; Balt Extrusion) for its delivery. A distinct advantage of this delivery system in contrast to other ⇑ Corresponding author. Tel.: +1 713 798 6151. E-mail address: [email protected] (S.B. Murthy). 0967-5868/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2013.07.006
stents is that it allows resheathing and repositioning, even when up to 90% of it has been deployed [5]. While it has not yet received regulatory approval in the USA for monotherapy, it is widely used as a stand-alone treatment in Europe. Initial results with the SILK stent suggested a promising rate of aneurysm occlusion, morbidity and mortality [5–8] but recent reports have highlighted a higher risk of thromboembolic complications and delayed aneurysm rupture, especially following treatment of giant aneurysms [9,10]. To the best of our knowledge there is no comprehensive article exclusively on the clinical outcomes of SFD. We present a systematic review of the published literature to evaluate aneurysm occlusion rates, mortality and procedure-related complication rates for intracranial aneurysms treated with the SFD. 2. Materials and methods 2.1. Search strategy An English language literature search was performed on PubMed, Ovid Medline, Ovid EMBASE and Web of Science, from
204
S.B. Murthy et al. / Journal of Clinical Neuroscience 21 (2014) 203–206
January 2005 to March 2013. A combination of the following keywords was used: ‘‘intracranial aneurysms’’, ‘‘SILK flow diverter’’, and ‘‘flow diverters’’. The bibliographies of identified studies were searched for additional referenced studies, and this method was repeated until no further studies were found. The pre-specified inclusion criteria were n > 10 patients, SILK treatment without other flow diverter use (additional coiling/stent placement patients included), and studies with information on complications and mortality.
Table 2 Angiographic distribution of 293 aneurysms reported in the relevant literature
2.2. Data extraction Data were collected by one author (S.B.M) using a standardized data-extraction spreadsheet in Excel (Microsoft, Redmond, WA, USA). Data on baseline variables included demographics, number of aneurysms treated and total number of SILK devices used. Aneurysm characteristics collected included location, diameter, size and dome to neck ratio. Aneurysms were classified as small (<10 mm), large (10–25 mm) or giant (>25 mm). Procedural complications were categorized as peri-procedural or delayed complications. A complication that occurred within 7 days of the procedure was considered peri-procedural, while those occurring beyond this time frame were considered delayed. These included acute ischemic stroke, transient ischemic attack (TIA), intracranial hemorrhage (ICH), subarachnoid hemorrhage, parent artery occlusion/ stenosis, in-stent stenosis (ISS) and other complications such as mass effect and retroperitoneal hematoma. Mortality rates for individual studies were obtained, and a cumulative mortality rate was subsequently calculated. The main outcome measure was aneurysm occlusion rate (AOR) at 12 months following SILK placement. Only patients with complete aneurysm occlusion were considered.
Angiographic distribution
No. of aneurysms
%
Extradural ICA Intradural ICA Anterior cerebral artery Middle cerebral artery P Com Basilar artery Vertebral artery PICA PCA SCA Others
76 147 14 12 7 18 5 2 2 1 9
26 50 4.8 4.1 2.3 6.1 1.7 0.7 0.7 0.3 3.3
ICA = internal carotid artery, No. = number, P Com = posterior communicating artery, PCA = posterior cerebral artery, PICA = posterior inferior cerebellar artery, SCA = superior cerebellar artery.
73.8–83.4%). The mean age was 52.7 years. One study failed to mention the mean age [11]. 3.2. Aneurysm characteristics We included a total of 317 aneurysms in this review, of which nearly 87% (n = 275, 95% CI: 83–90.5%) were found in the anterior circulation and the remaining 13% (n = 42, 95% CI: 9.5–16.9%) were present in the posterior circulation. The angiographic distribution of the aneurysms is summarized in Table 2. For the sake of homogeneity of data, the internal carotid artery (ICA) aneurysms were divided into extradural and intradural segments. The extradural portion of the ICA included the petrous and cavernous segments, while the intradural portion included the paraophthalmic and supraclinoid segments. In terms of size, 44.4% of the aneurysms were classed as large (n = 130, 95% CI: 38.7–50.1%), 37.9% (n = 111, 95% CI: 32.4–43.5%) were classed as small, and 17.7% (n = 52, 95% CI: 13.3–22.1%) were giant aneurysms. The main outcome measure was the 12 month AOR. Only one study did not report the AOR at 12 months, and was excluded from the calculation of the cumulative AOR [7]. Angiographic follow-up information at 12 months was available for 264 aneurysms. The cumulative
3. Results 3.1. Patient demographics The search resulted in 109 articles of which a total of eight studies met the inclusion criteria. The patient demographics are listed in Table 1. We included 285 patients with 317 aneurysms. There were 224 female patients (78.6%, 95% confidence interval [CI]:
Table 1 Demographics and aneurysm characteristics of patients treated with SILK flow diverter (Balt Extrusion, Montmorency, France) Posterior circulation
Small aneurysms (<10 mm)
Large aneurysms (10–25 mm)
Giant aneurysms (>25 mm)
Aneurysms occluded at 12 months, n (%)
26
5
17
12
2
20/29 (69%)
77
68
9
29
30
18
59/70 (84.3)
25
23
2
5
10
10
15/19 (78.9)
58
20 (71.4) 28
21
7
3
20
5
16/20 (80%)
24
55.3
20 (83)
24
19
5
NA
NA
NA
16/23 (69.6)
19
62.1
15 (78.9) 19
16
3
2
17
0
NA
22
53
19 (86.4) 26
19
7
13
12
1
18/21 (85.7%)
76
49.1
58 (76.2) 87
83
4
42
29
16
72/82 (87.9%)
285
52.7
224 (78.6%)
275 (86.8%) 42 (13.2%)
111 (37.9%)
130 (44.4%)
52 (17.7%)
216/264 (81.8%)
Study
No. of Mean Females, pts age, years n (%)
Total Anterior aneurysms circulation
Lubicz et al. [19] Berge et al. [27] Leonardi et al. [11] Maimon et al. [5] Tahtinen et al. [6] Shankar et al. [7] Wagner et al. [28] Vellioglu et al. [8] Summary
26
48
17 (65.4) 31
65
54
51 (78)
25
NA
24 (96)
28
317
NA = not available, No. = number, pts = patients.
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12 month AOR was 81.8% (95% CI: 77.1–86.5%) with complete occlusion in 216 aneurysms. 3.3. Complications The peri-procedural and delayed complications are listed in Table 3. The peri-procedural complication rate was 12.5% (n = 36, 95% CI: 8.7–16.3%) and the delayed complication rate was 9.9% (n = 28, 95% CI: 6.4–13.4%). The overall observed mortality rate was 4.9% (n = 14, 95% CI: 2.4–7.4%). Ischemic complications occurred in a total of 29 patients, including both stroke (7.7%, 95% CI: 4.6–10.8%) and TIA (2.5%, 95% CI: –0.7–4.3%). ICH occurred in four patients (1.4%, 95% CI: 0.04–2.8%). The delayed aneurysm rupture rate was 3.5% (n = 10, 95% CI: 1.4–5.6%). ISS was observed in 17 patients (5%, 95% CI: 2.4–7.4%) and most of the patients had a stent luminal occlusion <50%. There was a total of 29 patients with parent artery occlusion/stenosis (95% CI: 6.7–13.7%). Other complications included acute hydrocephalus, mass effect and carotid-cavernous fistula formation. 4. Discussion Our systematic review on SFD included a total of 285 patients with 317 aneurysms. The main outcome measure, 12 month AOR, was 81.8%. This is comparable to the AOR seen with the other flow diverter currently in clinical use, the Pipeline Embolization Device (PED; ev3 Endovascular, Plymouth, MN, USA). Our previous systematic review on PED showed a 6 month AOR of 79.7% [12], with progressive occlusion of the aneurysm to 81–84% by the end of 12 months [13,14]. The AOR is conspicuously higher with flow diverters in comparison with alternative treatment strategies like stent-assisted coiling. Shapiro et al. reported an AOR of 61% at variable follow-up times with stent-assisted coiling [15]. Flow diverters also appear to have minimal risk of aneurysm recurrence [1], compared to 14% with stent-assisted coiling [15] and a rate of 20–33.5% with coils alone [16,17]. In the series reported by Kulcsar et al. [18] and Lubicz et al., [19] no recanalization or reduction of occlusion status occurred, while only two patients showed a reduction in the degree of aneurysm occlusion in the SILK registry group [18]. Based on these encouraging results, the use of SFD has gradually been broadened from classical indications such as wide-neck large or fusiform aneurysms to include smaller aneurysms and also aneurysms located at bifurcations [5].
On the other hand, existing literature on SILK shows an increased rate of complications compared to PED. We calculated a peri-procedural complication rate of 12.5% and a delayed complication rate of 9.9%. In a similar review on PED, the peri-procedural complication rate was 5.7%, while the delayed complication rate was 1.9%. A noteworthy observation is that mortality is almost double with SFD (5%) compared to PED (2.3%) [12]. Interestingly, in March 2010, the manufacturer of SILK issued a field safety notice following deaths in eight patients from delayed aneurysm rupture [10]. All these patients had aneurysms with a diameter ranging from 18 to 33 mm. Purported mechanisms for aneurysm rupture include insufficient flow diversion leading to a more dangerous intra-aneurysmal flow pattern, and proteolytic enzymes released by the organizing thrombus in the aneurysmal sac causing vessel wall breakdown [20]. SFD is also thought to be more thrombogenic compared to conventional stents [8], as evidenced by a 5% rate of in-stent stenosis. But it is unclear how much of this is because of a wide heterogeneity in the antiplatelet regime following the use of flow diverters. The lower radial force exerted by SFD relative to other devices [20] also increases the risk of device migration and vessel occlusion as evidenced in many studies [6,19]. Owing to these risks, the use of SFD at vessel bifurcations remains a concern [19]. To our knowledge, there are only two studies providing a head to head comparison between SFD and PED [21,22]. They showed comparable rates of procedure-related complications and clinical outcomes including mortality. At present, two major multi-center randomized clinical trials have been planned to compare coiling and flow diverters. One is the multi-center randomized trial on selective endovascular aneurysm occlusion with coils versus parent vessel reconstruction using the SILK flow diverter (MARCO POLO) [23], and the other is the endovascular treatment of intracranial aneurysm with PED versus coils with or without stents (EVIDENCE) trial [24]. Currently underway is the Complete Occlusion of Coilable Aneurysms (COCOA) study, a randomized, multi-center study comparing coiling to the PED for treating small paraclinoid aneurysms (aneurysm diameter < 10 mm and neck diameter < 4 mm) [25]. The safety endpoint is death and ipsilateral stroke, and the effectiveness endpoint is assessed with 6 month complete aneurysmal occlusion [25]. Another trial, Flow Diversion in Intracranial Aneurysm Treatment (FIAT), comparing outcomes between flow diversion and best standard treatment (conservative, coiling or stenting) is also in the recruitment phase [26].
Table 3 Complications associated with the SILK flow diverter (Balt Extrusion, Montmorency, France) Study
Stroke
TIA
ICH
Parent artery occlusion
In-stent thrombosis
Aneurysm rupture
Mortality
Peri-procedural complications
Delayed complications
Lubicz et al. [19] Berge et al. [27] Leonardi et al. [11] Maimon et al. [5] Tahtinen et al. [6] Shankar et al. [7] Wagner et al. [28] Vellioglu et al. [8] Summary
3
0
0
8
1
1
1
6
4
6 0
2 0
1 3
6 0
5 0
3 1
2 2
5 4
7 0
4
0
0
1
2
0
1
5
2
2
0
0
4
1
0
1
1
1
2
1
0
2
0
0
2
2
4
2
2
0
4
4
0
1
4
6
3
2
0
4
4
5
4
9
4
22 (7.7%)
7 (2.5%)
4 (1.4%)
29 (10.2%)
17 (4.9%)
10 (3.5%)
14 (4.9%)
36 (12.5%)
28 (9.9%)
ICH = intracerebral hemorrhage, TIA = transient ischemic attack.
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Our study has a few noteworthy limitations. Firstly, we included both prospective and retrospective studies, which could affect the quality of the data. Secondly, only English language articles were included and it is possible that some good quality studies in other languages may have been excluded. A striking feature was the inconsistencies in the duration of antiplatelet therapy, and also regarding monotherapy versus dual therapy. Outcome measures of neurological function such as the modified Rankin score were not mentioned in most studies, precluding assessment of cumulative clinical outcomes with SFD. 5. Conclusions Flow diverters have added a new dimension to the treatment of intracranial aneurysms, ranging from the small, uncomplicated ones to the large, giant, wide-necked aneurysms. The current data suggest a distinctly higher AOR in comparison to other alternative endovascular treatment strategies. The SFD, despite offering >80% AOR, has a higher incidence of complications, particularly thromboembolic events and aneurysm rupture relative to PED. Randomized prospective trials are currently underway to further evaluate the clinical outcomes with the flow diverters. Conflicts of interest/disclosure The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References [1] Szikora I, Berentei Z, Kulcsar Z, et al. Treatment of intracranial aneurysms by functional reconstruction of the parent artery: the Budapest experience with the pipeline embolization device. AJNR 2010;31:1139–47. [2] Lylyk P, Miranda C, Ceratto R, et al. Curative endovascular reconstruction of cerebral aneurysms with the pipeline embolization device: the Buenos Aires experience. Neurosurgery 2009;64:632–42 [discussion 642–633; quiz N6]. [3] Canton G, Levy DI, Lasheras JC, et al. Flow changes caused by the sequential placement of stents across the neck of sidewall cerebral aneurysms. J Neurosurg 2005;103:891–902. [4] Lopes D, Sani S. Histological postmortem study of an internal carotid artery aneurysm treated with the Neuroform stent. Neurosurgery 2005;56:E416 [discussion E416]. [5] Maimon S, Gonen L, Nossek E, et al. Treatment of intra-cranial aneurysms with the SILK flow diverter: 2 years’ experience with 28 patients at a single center. Acta Neurochir 2012;154:979–87. [6] Tahtinen OI, Manninen HI, Vanninen RL, et al. The silk flow-diverting stent in the endovascular treatment of complex intracranial aneurysms: technical aspects and midterm results in 24 consecutive patients. Neurosurgery 2012;70:617–23 [discussion 623–614]. [7] Shankar JJ, Vandorpe R, Pickett G, et al. SILK flow diverter for treatment of intracranial aneurysms: initial experience and cost analysis. J Neurointerv Surg 2013 [Epub ahead of print]. [8] Velioglu M, Kizilkilic O, Selcuk H, et al. Early and midterm results of complex cerebral aneurysms treated with Silk stent. Neuroradiology 2012;54:1355–65.
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