Endovascular Treatment of Intracranial Aneurysms With Flow

Original Contributions
Endovascular Treatment of Intracranial Aneurysms
With Flow Diverters
A Meta-Analysis
Waleed Brinjikji, MD; Mohammad H. Murad, MD, MPH; Giuseppe Lanzino, MD;
Harry J. Cloft, MD, PhD; David F. Kallmes, MD
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Background and Purpose—Flow diverters are important tools in the treatment of intracranial aneurysms. However, their
impact on aneurysmal occlusion rates, morbidity, mortality, and complication rates is not fully examined.
Methods—We conducted a systematic review of the literature searching multiple databases for reports on the treatment
of intracranial aneurysms with flow-diverter devices. Random effects meta-analysis was used to pool outcomes of
aneurysmal occlusion rates at 6 months, and procedure-related morbidity, mortality, and complications across studies.
Results—A total of 29 studies were included in this analysis, including 1451 patients with 1654 aneurysms. Aneurysmal
complete occlusion rate was 76% (95% confidence interval [CI], 70%–81%). Procedure-related morbidity and mortality
were 5% (95% CI, 4%–7%) and 4% (95% CI, 3%–6%), respectively. The rate of postoperative subarachnoid hemorrhage
was 3% (95% CI, 2%–4%). Intraparenchymal hemorrhage rate was 3% (95% CI, 2%–4%). Perforator infarction rate was
3% (95% CI, 1%–5%), with significantly lower odds of perforator infarction among patients with anterior circulation
aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.01; 95% CI, 0.00–0.08; P<0.0001).
Ischemic stroke rate was 6% (95% CI, 4%–9%), with significantly lower odds of perforator infarction among patients
with anterior circulation aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.15; 95% CI,
0.08–0.27; P<0.0001).
Conclusions—This meta-analysis suggests that treatment of intracranial aneurysms with flow-diverter devices is feasible
and effective with high complete occlusion rates. However, the risk of procedure-related morbidity and mortality is
not negligible. Patients with posterior circulation aneurysms are at higher risk of ischemic stroke, particularly
perforator infarction. These findings should be considered when considering the best therapeutic option for intracranial
aneurysms. (Stroke. 2013;44:00-00.)
Key Words: endovascular treatment ■ interventional neuroradiology
■ subarachnoid hemorrhage
F
low-diverter devices are new, important tools in the treatment of intracranial aneurysms.1 Several single- and multicenter studies have demonstrated acceptable rates of aneurysm
occlusion, morbidity, and mortality for patients treated with
flow diverters.2–30 These devices are being deployed in greater
numbers of patients with more complex aneurysm morphologies and locations.9,12,18,22,25,29 With increasing experience,
some of the limitations and unexpected complications of flow
diverters have been recognized. These include intraparenchymal hemorrhage (IPH), postprocedural subarachnoid hemorrhage (SAH), as well as ischemic stroke.8
Improved understanding of safety and efficacy profiles associated with flow-diverter treatment of intracranial aneurysms
would help guide practitioners in selection and follow-up of
patients treated with these devices. We conducted a systematic
review and meta-analysis of the literature regarding aneurysmal
■
intracranial aneurysm
occlusion rates and procedure-related complication rates for
intracranial aneurysms treated with flow diverters.
Methods
A comprehensive review of the literature was performed using the
keywords “Intracranial aneurysm”, “divert”, “diversion”, “silk”,
“pipeline,” and “pipeline embolization device” to search Pubmed,
Ovid Medline, Ovid EMBASE, Scopus, and Web of Science database. Inclusion criteria were the following: English language, >5 patients, studies published between January 2005 and September 2012,
and data on postoperative complications and aneurysmal occlusion
rates. The exclusion criteria were the following: case reports, in vitro
or cadaveric studies, review articles, guidelines, technical notes, and
disaster series (series in which all patients were selected because of
certain major complication).
The electronic search was supplemented by contacting experts
in the field and reviewing the bibliographies of included studies for
relevant publications. Abstracts, methods, results, figures, and tables
Received September 24, 2012; final revision received November 11, 2012; accepted November 13, 2012.
From the Department of Neurosurgery (D.F.K., H.J.C.), Department of Radiology, Mayo Clinic, Rochester, MN (W.B., G.L., H.J.C., D.F.K.); Center for
Science of Healthcare Delivery, Mayo Clinic, Rochester, MN (M.H.M.); and Department of Neurosurgery, Mayo Clinic, Rochester, MN (G.L.).
Correspondence to Waleed Brinjikji, MD, Mayo Clinic, OL 1–115, 200 SW First St, Rochester, MN 55905. E-mail [email protected]
© 2013 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.112.678151
1
2 Stroke February 2013
of full text were searched for data on aneurysmal occlusion rates,
procedure-related morbidity and mortality, and procedure-related
complications.
Aneurysm occlusion was defined as complete occlusion at 6
months. We studied the effect of aneurysm size and aneurysmal occlusion rates, stratifying aneurysms as small (<10 mm), large (10 mm
≥aneurysm size ≤25 mm), or giant (>25 mm).
Procedure-related complications were stratified as total, early
(within ≤30 days), and late (>30 days). Complications studied included total, early, and late IPH; total, early, and late ischemic stroke;
total perforator infarction; and total, early, and late SAH. We examined the association between aneurysm size (small versus large/giant)
and aneurysm location (anterior versus posterior) and the total rates
of each of the studied complications.
Statistical Analysis
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We estimated from each study the cumulative incidence (event rate)
and 95% confidence interval (CI) for each outcome. Event rates were
pooled across studies using random effects meta-analysis.31 Subgroup
interactions (ANCOVA) were conducted using an interaction test as
described by Altman.32 Heterogeneity across studies was evaluated
using the I2 statistic.33
Results
Study Selection
A total of 505 articles were retrieved, of which 29 met our
inclusion criteria (Table 1). Eighteen studies were retrospective case series, and 11 were prospective single-arm studies.
Twenty-six studies reported aneurysmal occlusion rates; 29
reported procedure-related morbidity, mortality, and complication rates; and 26 reported both. We included 1451 patients
and 1654 treated aneurysms. The mean (±SD) number of
patients and treated aneurysms per study were 50.0±59.4 and
57.0±69.9, respectively.
Study Outcomes
Complete occlusion rate was 76% (95% CI, 70%–81%) at 6
months. Complete occlusion rate was 80% (95% CI, 69%–
88%) for small aneurysms, 74% (95% CI, 63%–83%) for
large aneurysms, and 76% (95% CI, 53%–90.0%) for giant
aneurysms (P=0.83).
Procedure-related permanent morbidity rate was 5% (95%
CI, 4%–7%), and procedure-related mortality rate was 4%
(95% CI, 3%–6%). IPH rate was 3% (95% CI, 2%–4%), with
3% (95% CI, 2%–4%) experiencing early IPH and 2% (95%
CI, 1%–3%) experiencing late IPH. Aneurysm size and location were not significantly associated with IPH rate (OR, 0.43;
95% CI, 0.11–1.65; P=0.24 and OR, −1.73; 95% CI, 0.62–
4.68, respectively; P=0.35).
SAH rate was 4% (95% CI, 3%–5%), with 3% (95% CI,
2%–5%) experiencing early SAH and 2% (95% CI, 1%–
3%) experiencing late SAH. Patients with small aneurysms
had a significantly lower rate of postoperative SAH (OR,
0.10; 95% CI, 0.02–0.42; P<0.0001). Aneurysm location
was not associated with SAH rate (OR, 1.89; 95% CI, 0.43–
8.21; P=0.55).
Total ischemic stroke rate was 6% (95% CI, 4%–9%), with
5% (95% CI, 3%–8%) experiencing early ischemic stroke
and 3% (95% CI, 2%–4%) experiencing late ischemic stroke.
Patients treated for smaller aneurysms had lower rates of
ischemic stroke than their large/giant counterparts (OR, 0.26;
95% CI, 0.07–0.91; P=0.03). Patients treated for anterior
circulation aneurysms also had significantly lower ischemic
stroke rates than those treated for posterior circulation aneurysms (OR, 0.15; 95% CI, −0.08 to 0.27; P<0.0001). Perforator
infarction rate was 3% (95% CI, 1%–5%). Patients with anterior circulation aneurysms had significantly lower perforator
infarction rates than their posterior circulation counterparts
(OR, 0.01; 95% CI, 0.00–0.08; P<0.0001). Aneurysm size
was not associated with perforator infarction risk (OR, 0.33;
95% CI, 0.09–1.25; P=0.13).
Analyses of aneurysm occlusion, total ischemic stroke,
and perforator infarction were associated with substantial
heterogeneity (I2 >50%), suggesting unexplained differences
in study populations and procedures. The remaining analyses
had minimal heterogeneity.
Table 2 summarizes outcomes independent of aneurysm
size and location. Table 3 summarizes clinical outcomes by
aneurysm size and location.
Discussion
Our meta-analysis demonstrated high occlusion rates for
aneurysms treated with flow diverters, irrespective of aneurysm
size. However, we also demonstrated that the complications
associated with flow diverter treatment are not negligible, with
morbidity and mortality rates of 5% and 4%, respectively. The
safety of flow diversion in small aneurysms was superior to
that of large aneurysms, with the latter associated with higher
rates of both ischemic infarction and SAH. Higher morbidity
in larger aneurysms may relate to the technical challenges as
well as the inherent instability of these lesions. We did not find
any specific aneurysm type associated with higher rates of IPH
but did find an alarmingly high association between perforator
infarction and posterior location of intracranial aneurysms.
These findings suggest that practitioners must be judicious in
selecting candidates for flow-diverter therapy, especially for
large or posterior circulation aneurysms.
Published aneurysmal complete occlusion rates are often
variable, ranging anywhere from 55% to 95%.4,24 In combining aneurysmal occlusion rates from 29 studies, our metaanalysis provides more representative data on aneurysmal
occlusion rates than any single study. Furthermore, in studying such a large sample, we had more power to detect differences in aneurysmal occlusion rates by size. This lends greater
validity to our finding that aneurysmal occlusion rates were
high regardless of size. This finding is extremely important
because the current dogma in endovascular intracranial aneurysm treatment is that smaller aneurysms have better occlusion rates than larger aneurysms.34 The finding that even giant
aneurysms have such high occlusion rates provides important
implications for those looking to stem the rates of aneurysm
recurrence among this population.
Among larger studies, mortality rates have ranged from 0%
to 7%,2,28 whereas morbidity has ranged from 0% to 12%.2,13
Our meta-analysis provides more representative data on morbidity, mortality, and complication rates associated with flowdiverter treatment. Another advantage of this meta-analysis is
its increased power to detect differences in complication rates
Brinjikji et al Flow-Diverter Meta-Analysis 3
Table 1. Studies Included in Meta-Analysis
Author
Title
Journal
Year
Study Design
No. of
Patients
Aneurysms
Treated
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Barros Faria et al
The role of the pipeline embolization
device for the treatment of dissecting
intracranial aneurysms
American Journal of
Neuroradiology
2011
Retrospective
23
23
Berge et al
Flow-diverter silk stent for the treatment
of intracranial aneurysms; 1-year followup in a multicenter study
American Journal of
Neuroradiology
2012
Retrospective
65
77
Briganti et al
Italian multicenter experience with
flow-diverter devices for intracranial
unruptured aneurysm treatment
with periprocedural complications-a
retrospective data analysis
Neuroradiology
2012
Retrospective
273
295
Byrne et al
Early experience in the treatment of
intracranial aneurysms by endovascular
flow diversion: a multicentre prospective
study
PLoS ONE
2010
Prospective single-arm
interventional cohort
70
70
Chan et al
Pipeline embolization device for wide
necked internal carotid artery aneurysms
in a hospital in Hong Kong: preliminary
experience
Hong Kong Medical
Journal
2011
Retrospective
9
13
Cirillo et al
The use of flow-diverting stents in the
treatment of giant cerebral aneurysms
The Neuroradiology
Journal
2012
Retrospective
9
9
Colby et al
Immediate procedural outcomes in 35
consecutive pipeline embolization cases:
a single-center single-user experience
Journal of
Neurointerventional
Surgery
2012
Retrospective
34
41
Cruz et al
Delayed ipsilateral parenchymal
hemorrhage following flow diversion
for the treatment of anterior circulation
aneurysms
American Journal of
Neuroradiology
2012
Retrospective
47
47
Deautschmann et al
Long-term follow-up after treatment of
intracranial aneurysms with the pipeline
embolization device: results from a single
center
American Journal of
Neuroradiology
2012
Prospective single-arm
interventional cohort
12
12
Fischer et al
Pipeline embolization device for
neurovascular reconstruction; initial
experience in the treatmnet of 101
intracranial aneurysms and dissections
Neuroradiology
2011
Retrospective
88
101
Kulcsar et al
High-profile flow-diverter (silk)
implantation in the basilar artery: efficacy
in the treatment of aneurysms and the
role of perforators
Stroke
2010
Retrospective
12
12
Leonardi et al
Treatment of intracranial aneurysms using Interventional
flow-diverting silk stents balt: a singleNeuroradiology:
center experience
Journal of Perither
2011
Retrospective
25
25
Lubicz et al
Pipeline flow-diverter stent for
endovascular treatment of intracranial
aneurysms: preliminary experience in 20
patients with 27 aneurysms
World Neurosurgery
2011
Retrospective
20
27
Lubicz et al
Flow-diverter stent for the endovascular
treatment of intracranial aneurysms: a
prospective study in 29 patients with 34
aneurysms
Stroke
2010
Prospective single-arm
interventional cohort
29
34
Lylyk et al
Curative endovascular reconstruction
of cerebral aneurysms with the pipeline
embolization device: the buenos aires
experience
Neurosurgery
2009
Prospective single-arm
interventional cohort
53
63
Maimon et al
Treatment of intracranial aneurysms with
the SILK flow diverter: 2 years experience
with 28 patients at a single center
Acta Neurochir
2012
Retrospective
28
32
(continued)
4 Stroke February 2013
Table 1. Continued
Author
Title
Journal
Year
Study Design
No. of
Patients
Aneurysms
Treated
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McAuliffe et al
Immediate and midterm results following
treatment of unruptured aneurysms with
the pipeline embolization device
American Journal of
Neuroradiology
2012
Prospective single-arm
interventional cohort
54
57
McAuliffe et al
Immediate and midterm results following American Journal of
treatment of recently ruptured intracranial Neuroradiology
aneurysms with the pipeline embolization
device
2012
Prospective single-arm
interventional cohort
11
11
Nelson et al
The pipeline embolization device for the
intracranial treatment of aneurysms trial
American Journal of
Neuroradiology
2011
Prospective single-arm
interventional cohort
31
31
Philips et al
Safety of the pipeline embolization device
in treatment of posterior circulation
anuerysms
American Journal of
Neuroradiology
2012
Prospective single-arm
interventional cohort
32
32
Pistocchi et al
Flow diverters at and beyond the level
of the circle of willis for the treatment of
intracranial aneurysms
Stroke
2012
Prospective single-arm
interventional cohort
26
30
Puffer et al
Patency of the ophthalmic artery after
flow-diversion treatment of paraclinoid
artery aneurysms
Journal of Neurosurgery
2012
Retrospective
19
20
Saatci et al
Treatment of intracranial aneurysms using American Journal of
pipeline flow-diverter embolization device: Neuroradiology
largest single-center experience with
long-term follow-up results
2012
Retrospective
191
251
Siddiqui et al
Panacea or problem: flow diverters in the
treatment of symptomatic large or giant
fusiform vertebrovascular aneurysms
Journal of Neurosurgery
2012
Prospective single-arm
interventional cohort
7
7
Szikora et al
Treatment of intracranial aneurysms by
functional reconstruction of the parent
artery: the Budapest experience with the
pipeline embolization device
American Journal of
Neuroradiology
2010
Retrospective
18
19
Tahtinen et al
Treatment of complex intracranial
aneurysms: technical aspects and
midterm results in 24 consecutive
patients
Neurosurgery
2011
Retrospective
24
24
Velioglu
Early and midterm results of complex
Neuroradiology
cerebral aneurysms treated with Silk stent
2012
Retrospective
76
87
Wagner et al
Treatment of intracranial aneurysms:
reconstruction of the parent artery with
flow-diverting (Silk) stent
2011
Retrospective
22
26
Yu et al
Midterm outcome of pipeline embolization Radiology
device for intracranial anuerysms-a
prospective study in 143 patients with
178 aneurysms
2012
Prospective single-arm
interventional cohort
143
178
Neuroradiology
by aneurysm size and location, thus allowing practitioners to
risk stratify potential patients.
One of the unanticipated and most feared complications
of flow diverters is aneurysm rupture after treatment with
these devices. The overall incidence of this complication is
unknown, although it is thought to be low and critically related
to the complexity of the treated aneurysm. Our meta-analysis
suggests that SAH from delayed aneurysm rupture occurs in
≈4% of patients treated with flow diverters, with significantly
higher rates among patients with large and giant aneurysms.
Aneurysm rupture at ≥1 month postoperative was a relatively
rare occurrence (2% of cases). Nonetheless, concerns regarding delayed rupture are so serious that Balt Extrusion issued
a medical device alert instructing practitioners not to use the
Silk flow diverter without coils owing to the potential for
patient death.15 Our study emphasizes that postoperative SAH
is a real and significant complication of flow-diverter patients,
especially for those with large or giant aneurysms. It is not
known at this point whether the practice of using endovascular coils in association with flow diverters in the treatment of
larger aneurysms has resulted in a decreased incidence of this
devastating complication.
IPH not associated with aneurysm rupture is another
dreaded and poorly understood complication of flow-diverter
treatment. Previous studies have reported rates ranging from
0% to 10% for this complication.2,4,8,19 We demonstrated a
Brinjikji et al Flow-Diverter Meta-Analysis 5
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Table 2. Outcomes for Endovascular Treatment of Intracranial
Aneurysms With Flow Diverters
Table 3. Outcomes by Aneurysm Size and Location
Outcome
Rate
95% CI
I2 (%)
Ischemic stroke
Complete aneurysmal occlusion ≥6 months
76.0
70.0–81.0
69.0
Procedure-related morbidity
5.0
4.0–7.0
15.0
Procedure-related mortality
4.0
3.0–6.0
35.0
SAH
SAH ≤30 days
3.0
2.0–5.0
0.0
SAH >30 days
2.0
1.0–3.0
0.0
SAH total
4.0
3.0–5.0
4.0
Perforator infarction
Intraparenchymal hemorrhage ≤30 days
3.0
2.0–4.0
0.0
Intraparenchymal hemorrhage >30 days
2.0
1.0–2.0
0.0
Intraparenchymal hemorrhage total
3.0
2.0–4.0
0.0
Intraparenchymal hemorrhage
Ischemic stroke ≤30 days
5.0
3.0–8.0
48.0
Ischemic stroke >30 days
3.0
2.0–4.0
0.0
Ischemic stroke total
6.0
4.0–9.0
56.0
Perforator infarction
3.0
1.0–5.0
60.0
CI indicates confidence interval; and SAH, subarachnoid hemorrhage.
3% rate of IPH among flow-diverter patients. The mechanism for IPH is unknown. Hemorrhagic transformation of
ischemic stroke, hemodynamic alteration from flow-diverter
placement, and dual antiplatelet therapy are proposed mechanisms.8 In our study, neither aneurysm size nor location was
associated with IPH rate. All studies included both pre operative and postoperative dual antiplatelet therapy; thus, we
could not examine any independent role this might play in
IPH formation. Further studies are needed to determine the
ultimate cause of IPH.
Ischemic stroke and perforator infarction are well-described
complications of flow-diverter treatment.35,36 We demonstrated
an ischemic stroke rate of 6%, with higher rates in posterior
circulation aneurysms and large/giant aneurysms. Ischemic
stroke is thought to result from thrombus formation along the
stent wall, leading to stent occlusion, parent artery occlusion,
or distal thromboembolic events.35,36 The higher rates of ischemic stroke among patients with large/giant aneurysms may be
related to the fact that, these aneurysms likely required more
flow-diverter devices to achieve successful occlusion and may
have been subject to longer operation times. Intraoperatively,
acute thrombus formation can be mitigated by prompt injection of Abciximab.27 However, in the long term, it is difficult
to reduce the risk of thromboembolic events associated with
flow-diverter treatment.
Perforator infarction in our meta-analysis was not uncommon and often led to devastating consequences. Perforator
vessels in the posterior circulation are at particularly high
risk for infarction relative to those in the anterior circulation.
This is likely because of the delicate perfusion and lack of
collaterals to brain stem structures. Many case series of posterior circulation aneurysms treated with flow diverters have
demonstrated this fact.12,21,25 Thus, given the relatively high
rate of this complication and the devastating consequences of
brain stem infarction, treatment of posterior circulation aneurysms in which perforator vessels could be involved should
be performed only when absolutely necessary. When possible,
deconstructive technique (parent vessel occlusion with flow
Outcome
Odds Ratio
95% CI
Aneurysm size (small/large vs giant)*
0.26
0.07–0.91
Aneurysm location (anterior vs posterior)*
0.15
0.08–0.27
Aneurysm size (small/large vs giant)*
0.10
0.02–0.42
Aneurysm location (anterior vs posterior)
1.89
0.43–8.21
Aneurysm size (small/large vs giant)
0.33
0.09–1.25
Aneurysm location (anterior vs posterior)*
0.01
0.00–0.08
Aneurysm size (small/large vs giant)
0.43
0.11–1.65
Aneurysm location (anterior vs posterior)
0.48
0.17–1.35
CI indicates confidence interval; and SAH, subarachnoid hemorrhage.
*Denotes statistically significant results. Odds ratio <1.0 favors the
characteristic mentioned first.
reversal) should be the first consideration for treatment of
large or giant basilar artery aneurysms.
This study has various limitations. Ecological bias (ie,
comparisons are made across studies and not within studies),
presence of publication bias, and statistical heterogeneity are
limitations that affect all meta-analyses. Our study also has
limitations because of the methodologic limitations of included
studies. A majority of the included studies were retrospective
case series. No prospective studies included were randomized
or included control groups. Many of the included studies had
a small sample size and incomplete follow-up data. Because a
majority of previously published studies did not stratify outcomes based on important variables, such as patient demographics, duration of antiplatelet therapy, aneurysm rupture
status, aneurysm subtype (secular versus fusiform), number
of devices deployed, use of concomitant coiling, and previous aneurysm treatment status, we were unable to control for
these findings in our analysis. Efficacy of flow-diverter treatment in treating compressive symptoms was rarely reported
in the included studies; thus, we were unable to determine the
efficacy of flow diverters in treatment of these symptoms. Our
findings represent a very wide spectrum of aneurysms and
clinical presentations, and thus our findings cannot be applied
to determine the risks and complications associated with treating individual patients or different subgroups of aneurysms
with flow diverters. Given the heterogeneity of the patients
and aneurysms in our study, our data cannot be used to compare the efficacy of flow-diverter technology versus treatments, such as coiling and clipping. Therefore, the overall
quality of evidence (strength of inference) presented in this
systematic review is considered to be low.
Conclusions
Our study suggests that treatment of intracranial aneurysms with
flow-diverter devices is feasible and effective with high complete occlusion rates. The rates of procedure-related morbidity and mortality
are not negligible. Patients with posterior circulation aneurysms are at
higher risk of ischemic stroke, particularly perforator infarction, and
patients with larger aneurysms are at increased risk of ischemic stroke
6 Stroke February 2013
and SAH. These findings should be considered when determining the
best therapeutic option for intracranial aneurysms.
Disclosures
Dr Cloft was the site PI at enrolling site for SAPPHIRE (Stenting
and Angioplasty with Protection in Patients and HIgh Risk for
Endarterectomy) registry sponsored by Cordis Endovascular, and Dr
Kallmes received a grant, ev3-funding for clinical trials and preclinical research and has pending grants from Penumbra, MicroVention,
Micrus, and Cordis. The other authors have no conflicts to report.
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Endovascular Treatment of Intracranial Aneurysms With Flow Diverters: A
Meta-Analysis
Waleed Brinjikji, Mohammad H. Murad, Giuseppe Lanzino, Harry J. Cloft and David F.
Kallmes
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Abstract
29
Abstract
Flow Diverter を用いた脳動脈瘤の血管内治療
メタアナリシス
Endovascular Treatment of Intracranial Aneurysms With Flow Diverters
A Meta-Analysis
Waleed Brinjikji, MD2; Mohammad H. Murad, MD, MPH3; Giuseppe Lanzino, MD2,4; Harry J. Cloft, MD,
PhD1,2; David F. Kallmes, MD1,2
1
Department of Neurosurgery, 2Department of Radiology, Mayo Clinic, Rochester, MN ; 3 Center for Science of Healthcare Delivery, Mayo Clinic,
Rochester, MN; and 4 Department of Neurosurgery, Mayo Clinic, Rochester, MN.
背景および目的：flow diverter は脳動脈瘤の治療において
重要な器具である。しかし，動脈瘤閉塞率，罹病率，死亡
率，および合併症の発生率に対する影響については完全に
は解明されていない。
方法：様々なデータベースで flow diverter を用いた脳動
脈瘤の治療に関する論文を検索した文献を系統的に調べ
た。ランダム効果メタ解析を用いて，6 カ月目の動脈瘤閉
塞率の転帰，手技が原因の罹病率，死亡率，および合併症
の発生率をすべての論文から収集した。
結果：合計 29 篇の論文をこの解析に含めた（患者は 1,654
箇の動脈瘤を有する 1,451 例）。動脈瘤の完全閉塞率は
76％であった［ 95％信頼区間（ CI ）
：70 ～ 81％］
。手技が原
因の罹病率は 5％（ 95％ CI：4 ～ 7％），死亡率は 4％
（ 95％
CI：3 ～ 6％）であった。術後のくも膜下出血発生率は 3％
（ 95％ CI：2 ～ 5％），脳実質内出血の発生率は 3％（ 95％
CI：2 ～ 4％）であった。穿通枝梗塞の発生率は 3％（ 95％
CI：l ～ 5％）で，前方循環動脈瘤患者の穿通枝梗塞のオッ
ズは，後方循環動脈瘤患者
（オッズ比＝ 0.01；95％ CI：0.00
～ 0.08；p ＜ 0.0001 ）と比較して有意に低かった。虚血性
脳卒中の発生率は 6％（ 95％ CI：4 ～ 9％）
で，前方循環動
脈瘤患者の穿通枝梗塞のオッズは後方循環動脈瘤患者と比
較して有意に低かった（オッズ比＝ 0.15；95％ CI：0.08
～ 0.27；p ＜ 0.0001 ）
。
結論：今回のメタアナリシスの結果，flow diverter を用い
た脳動脈瘤の治療は可能で，かつ効果的であり，高い完全
閉塞率を示した。しかし，手技が原因の罹病率や死亡率の
リスクは無視することはできない。後方循環動脈瘤患者で
は虚血性脳卒中のリスクが高く，特に，穿通枝梗塞のリス
クが高い。脳動脈瘤の最良の治療オプションを検討する際
にはこれらの知見を考慮する必要がある。
Stroke 2013; 44: 442-447
表 2 Flow Diverter を用いた脳動脈瘤の血管内治療の転帰
転帰
動脈瘤による完全閉塞 ≧ 6 ヵ月
％
95％ CI
l 2％
76.0
70.0 〜 81.0
69.0
表 3 動脈瘤のサイズと位置による転帰
転帰
オッズ比
95％ CI
虚血性脳卒中
治療が原因の罹病率
5.0
4.0 〜 7.0
15.0
動脈瘤のサイズ（小／大対巨大）*
0.26
0.07 〜 0.91
治療が原因の死亡率
4.0
3.0 〜 6.0
35.0
動脈瘤の位置（前方対後方）*
0.15
0.08 〜 0.27
SAH ≦ 30 日
3.0
2.0 〜 5.0
0.0
SAH ＞ 30 日
2.0
1.0 〜 3.0
0.0
動脈瘤のサイズ（小／大対巨大）*
0.10
0.02 〜 0.42
SAH，合計
4.0
3.0 〜 5.0
4.0
動脈瘤の位置（前方対後方）
1.89
0.43 〜 8.21
脳実質内出血 ≦ 30 日
3.0
2.0 〜 4.0
0.0
脳実質内出血＞ 30 日
2.0
1.0 〜 2.0
0.0
動脈瘤のサイズ（小／大対巨大）
0.33
0.09 〜 1.25
脳実質内出血，合計
3.0
2.0 〜 4.0
0.0
動脈瘤の位置（前方対後方）*
0.01
0.00 〜 0.08
動脈瘤のサイズ（小／大対巨大）
0.43
0.11 〜 1.65
動脈瘤の位置（前方対後方）
0.48
0.17 〜 1.35
虚血性脳卒中 ≦ 30 日
5.0
3.0 〜 8.0
48.0
虚血性脳卒中＞ 30 日
3.0
2.0 〜 4.0
0.0
虚血性脳卒中，合計
6.0
4.0 〜 9.0
56.0
穿通枝梗塞
3.0
1.0 〜 5.0
60.0
CI：信頼区間，SAH：くも膜下出血。
SAH
穿通枝梗塞
脳実質内出血
CI：信頼区間，SAH：くも膜下出血。
* 統計学的に有意な結果を指す。オッズ比が＜ 1.0 の場合，（　）内の前
者の方を支持する

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