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Review




                                     Comparison of endovascular and surgical treatments for
                                     intracranial aneurysms: an evidence-based review
                                     Adnan I Qureshi, Vallabh Janardhan, Ricardo A Hanel, Giuseppe Lanzino

 Lancet Neurol 2007; 6: 816–25       Intracranial aneurysms can be treated with endovascular or surgical techniques. We provide an objective comparison
Zeenat Qureshi Stroke Research       of these treatments, using data from single-centre studies, multicentre studies with and without independent outcome
          Center, Department of      ascertainment, and randomised clinical trials. We compared the outcomes of patients who were candidates for
        Neurology, University of
                                     endovascular treatment, surgical treatment, or both. In patients with ruptured intracranial aneurysms, rates of
 Minnesota, Minneapolis, MN,
            USA (A I Qureshi MD,     aneurysm obliteration were higher, and need for second treatment was lower, after surgery than after endovascular
    V Janardhan MD); Division of     treatment. However, in observational studies and randomised trials, outcome at discharge, at 2–6 months, and at
  Neurological Surgery, Barrow       1 year, and later survival, were all better after endovascular treatment than after surgery. The results suggest that the
          Neurological Institute,
                                     higher rates of incomplete obliteration and retreatment after endovascular treatment do not affect patients’ clinical
        St Joseph’s Hospital and
   Medical Center, Phoenix, AZ,      outcome. In observational studies of patients with unruptured intracranial aneurysms, discharge outcomes were
        USA (R A Hanel MD); and      better and hospital costs were lower after endovascular treatment than after surgery. These patients showed no
 Department of Neurosurgery,         difference between the two treatments in 1-year outcomes and later rebleeding, although few data were available for
 Illinois Neurological Institute,
 University of Illinois College of
                                     this comparison.
        Medicine, Peoria, IL, USA
                  (G Lanzino MD)     Introduction                                                            such as detachable coils and intravascular stents. However,
            Correspondence to:       Intracranial aneurysms are focal dilatations in medium-                 the use of these treatments varies considerably among
 Adnan I Qureshi, Department of      sized arteries. They are a substantial health problem, and              institutions and practitioners. National organisations and
       Neurology, University Of
                                     affect roughly 2% of the population worldwide.1 In 1937,                 medical institutions are trying to ensure that the new
     Minnesota, 12-100 Phillips
   Wangensteen Building, MMC         Walter Dandy performed the first surgical treatment of                   technology is adapted in a uniform and evidence-based
    295, 420 Delaware Street SE      an aneurysm using a vascular clip designed by Harvey                    way. Over the past 5 years, as endovascular treatments have
   Minneapolis, MN 55455, USA        Cushing.2,3 Subsequent advances in neurosurgical                        become more widely available, practitioners have been
      aiqureshi@hotmail.com
                                     techniques (eg, the development of operating                            constantly seeking comprehensive and objective sources
                                     microscopes, microsurgical instruments, improved clips,                 of information to help them select patients for a particular
                                     neuroanaesthesia, and perioperative management for                      treatment. In this article, we review: comparisons of
                                     complications such as hydrocephalus and symptomatic                     endovascular treatment with surgery; how evidence is
                                     vasospasm) enabled neurosurgeons to treat most cerebral                 being incorporated into professional guidelines; and
                                     aneurysms, and surgery was the predominant treatment                    implications for the future, including deficiencies in some
                                     for almost four decades. Attempts were made to place                    of the present data. Panel 1 shows how we have classified
                                     iron particles, detachable balloons, and platinum coils                 surgical and endovascular treatments.
                                     into intracranial aneurysms through endovascular routes1
                                     but, although such treatment was successful in some                     Pathophysiology and rates of aneurysm rupture
                                     patients, its applicability was limited by high rates of                Intracranial aneurysms result from degeneration of the
                                     particle migration, balloon deflation, and aneurysm                      arterial wall, which is caused by congenital and acquired
                                     rupture. In the late 1980s, Guglielmi and colleagues4                   medical defects8 and factors such as hypertension and
                                     developed a device in which a soft platinum coil soldered               cigarette smoking.9,10 Enlargement and rupture of
                                     onto a stainless steel wire was successfully delivered                  aneurysms results from interplay between continuing
                                     through a microcatheter into the aneurysm sac—the coil                  degeneration and haemodynamics. A major rupture can
                                     mass protected against rupture by buffering the                          be preceded by infiltration of the artery wall by fibrin and
                                     haemodynamic stress against the fundus of the                           leucocytes, bleb formation, and a minor haemorrhage.9,10
                                     aneurysm.5,6 The development and subsequent approval                    Some intracranial aneurysms rupture early in their
                                     of such detachable coils by the US Food and Drug                        development and are commonly detected as small
                                     Administration (FDA) in 1995 mandated a reassessment                    ruptured aneurysms (aneurysms that show early
                                     of intracranial aneurysm treatment.                                     vulnerability); others rupture late in their development
                                       Initially, endovascular treatment was used in patients                and are commonly detected in the unruptured stage,
                                     who were thought to be poor candidates for surgical                     rupturing only after growing to a critical size (aneurysms
                                     treatment,1,7 such as people who: had severe neurological               that show late vulnerability). The factors that cause
                                     deficits; had an aneurysm in the posterior circulation or in             aneurysms to have early rather than late vulnerability are
                                     the cavernous segment of internal carotid artery; were aged             unclear.
                                     75 years or over; presented 3–10 days after aneurysm                      The rupture rate of aneurysms varies with location, as
                                     rupture; or had active cerebral vasospasm. Over the past                reported by the International Study of Unruptured
                                     decade, treatment of intracranial aneurysms has evolved                 Intracranial Aneurysms (ISUIA), which investigated
                                     rapidly, with new developments in endovascular treatments               2686 unruptured, untreated intracranial aneurysms in


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1692 patients (mean follow-up 4·1 years).11 Patients who
did not have a history of subarachnoid haemorrhage who         Panel 1: Variations of surgical and endovascular treatments for intracranial aneurysms
had aneurysms in the anterior circulation (ie, in the          Surgical treatments
internal carotid artery, anterior communicating or             Direct clipping (clips vary in strength, shape, and size)
anterior cerebral artery, or middle cerebral artery) had       Direct clipping with decompression of the aneurysmal sac (can include thrombectomy)
cumulative 5-year rupture rates of 0%, 2·6%, 14·5%, and        Direct clipping with neuroprotection (barbiturate anaesthesia or hypothermia)
40% for aneurysms of less than 7 mm, 7–12 mm,                  Proximal ligation (abrupt or gradual) or trapping with or without use of bypass
13–24 mm, and 25 mm or greater, respectively. Rupture          Wrapping or coating
rates for aneurysms of the same sizes in the posterior         Direct clipping of remnant aneurysm following endovascular treatment
circulation and posterior communicating artery were
2·5%, 14·5%, 18·4%, and 50%, respectively. Patients            Endovascular treatments
with a history of subarachnoid haemorrhage had a 5-year        Detachable coil placements (coils vary in strength, shape, and size)
cumulative rupture rate of 1·5% for aneurysms of less          Detachable coil placements with temporary balloon assistance
than 7 mm in the anterior circulation, compared with           Detachable coils and intravascular stent placement
3·4% for aneurysms of the same size in the posterior           Liquid embolic agent injection with intravascular balloon or stent assistance
circulation and posterior communicating artery. The            Occlusion of parent vessel
reason for the different rates of rupture between the           Detachable coil placements in remnant aneurysm following surgical treatment
anterior and posterior circulation is unclear.
  There are few data on the risk of rupture 5 years after    and associated outcomes in various settings. However,
detection of an unruptured aneurysm. Juvela and              the comparative value of these studies is limited by
colleagues12 followed 142 patients with 181 unruptured       prominent heterogeneity in selection of patients and
aneurysms for a median period of 20 years (range 1–39        imbalances in baseline characteristics between the two
years). Six patients had a single symptomatic aneurysm,      treatment groups. Some single-centre studies have
five had a single incidentally discovered aneurysm, and       reported higher rates of incomplete obliteration with
131 had a history of rupture and subsequent treatment of     endovascular treatment than with surgery,16,17 although
another intracranial aneurysm. During 2575 person-           the effect of incomplete obliteration on overall outcome
years of follow-up, there were 33 first-time episodes of      was small, and there was no difference in risk of early
haemorrhage from previously unruptured aneurysms,            rebleeding between the treatment groups.15,17 Studies that
with an average yearly incidence of 1·3%. The cumulative     reported better outcomes with surgery also reported
rate of rupture among these 142 patients was 10·5% at        more unfavourable baseline characteristics in patients
10 years, and 30·3% at 30 years.                             who received endovascular treatment.21,22 Conversely, in
  Following rupture of an intracranial aneurysm,             studies that used endovascular treatment as the first
recurrent rupture and subarachnoid haemorrhage occur         choice,16,17 many patients who were considered unsuitable
with much higher frequency. For example, Jane and            for endovascular treatment subsequently underwent
colleagues13 reported that the rate of rebleeding among      surgery.
patients with ruptured aneurysms was 50% within the            Johnston and colleagues14 reduced the effects of these
first 6 months and 3% per year thereafter. The goal of        imbalances between baseline characteristics using a
obliterative treatment is to prevent primary subarachnoid    blinded comparison of patients with unruptured
haemorrhage in patients with unruptured aneurysms,           intracranial aneurysms who received surgical (n=68) or
and recurrent subarachnoid haemorrhage in patients           endovascular (n=62) treatment. All 130 aneurysms were
with ruptured aneurysms.                                     judged by a panel of neurosurgeons and neuro-
                                                             interventional radiologists to be treatable by either
Comparisons of endovascular and surgical                     surgery or endovascular treatment. A higher frequency
treatments                                                   of post-procedural disability (score on the modified
Single-centre comparisons                                    Rankin scale [mRS] ≥2) was reported in patients who
An important point to note before we compare treatments      underwent surgery compared with those who underwent
for intracranial aneurysms is that some patients are         endovascular treatment (25% vs 8%). The length of stay
candidates for surgery only or endovascular treatment        in hospital, number of days in intensive care, and hospital
only, whereas for other patients, either treatment is an     costs were all greater for surgical patients. There were
acceptable option. This distinction depends on the           three delayed subarachnoid or intracranial haemorrhages
clinical condition of the patient, the morphology and        in the endovascular group and one in the surgical group
location of the aneurysm, and institutional expertise.       after follow-up of 3·9 years per patient.
Single-centre studies of endovascular and surgical
treatments14–25 (table 1) are valuable because the overall   Multicentre comparisons
treated population and periprocedural care do not vary       Observational studies that use multicentre databases
within each study. These studies thus provide an estimate    show consistently lower rates of in-hospital death and
of the proportion of patients treated with each modality     disability after endovascular treatment than after


http://neurology.thelancet.com Vol 6 September 2007                                                                                                  817
Review




                                       surgery.26,27 One procedure cannot be said to be better                        Adverse outcomes (in-hospital death, or discharge to a
                                       than another without knowledge of the baseline                                 nursing home or rehabilitation hospital) were more
                                       characteristics that affect outcome, but, as reported in                        frequent in the 1669 patients treated with surgery (25%)
                                       the single-centre studies, shorter hospital stays and                          than in the 400 who received endovascular therapy
                                       lower hospital costs lend support to the use of                                (10%). In-hospital death was more frequent after
                                       endovascular treatment in selected patients. Johnston                          surgery than after endovascular treatment (3·5% vs
                                       and colleagues26 compared complications of surgical and                        0·5%), and length of stay and hospital costs were
                                       endovascular treatment for unruptured intracranial                             greater after surgery. During the study period, adverse
                                       aneurysms at 60 hospitals in the US University Health                          outcomes declined for endovascular therapy (26% in
                                       System Consortium between 1994 and 1997. Adverse                               1991 vs 4% in 1998) but not for surgery (26% in 1991 vs
                                       outcomes, defined as in-hospital death or transfer to a                         21% in 1998).
                                       nursing home or rehabilitation hospital, were more                               Berman and colleagues28 evaluated the effect of
                                       common in 2357 patients who underwent surgery (19%)                            hospital characteristics on outcome in 2200 patients
                                       than in 255 who received endovascular treatment (11%).                         with ruptured cerebral aneurysms and 3763 patients
                                       In-hospital mortality was higher in surgical patients                          with unruptured aneurysms treated in New York state,
                                       (2·3% vs 0·4%) but there was no difference in the                               USA, from 1995 to 2000. More frequent use of
                                       multivariate analysis. Lengths of stay and hospital costs                      endovascular treatment in a hospital was associated
                                       were greater for surgical patients after adjustment for                        with fewer adverse outcomes (death or discharge to a
                                       confounding factors.                                                           rehabilitation hospital or long-term facility). Hospital
                                         Johnston and co-workers27 reviewed 2069 patients                             procedural volume and the propensity to use
                                       with unruptured intracranial aneurysms using a state-                          endovascular treatment were both independently
                                       wide database of hospital discharges in California, USA.                       associated with a good outcome.

                     Aneurysm            Endovascular          Surgery                 Imbalance between treatment             Conclusion
                     characteristics     treatment                                     groups
                                         n      Good outcome   n        Good outcome
  Kaku, 2007    24
                     79 ruptured          47 81%                32      78%            None documented                         A team of experts in microsurgery and endovascular treatment
                                                                                                                               should assess each aneurysm
  Helland,           All ruptured         83 66%               203      48%            None documented                         Endovascular treatment led to better clinical outcome than did
  200625                                                                                                                       surgery
  Taha, 200622       53 ruptured and         71 80%            62       66%            Endovascular group had worse            Endovascular treatment is a safe alternative to surgery for both
                     80 unruptured                                                     baseline characteristics                ruptured and unruptured aneurysms.
  Kato, 200521       All ruptured         59 44%               120      69%            Endovascular group had worse            Surgery led to better outcome than did endovascular treatment in
                                                                                       baseline characteristics                patients with poor-grade aneurysms
  Hoh, 200423        All ruptured        102 33%               413      55%            Endovascular group had worse            Surgery led to better outcome and lower mortality at discharge than
                                                                                       baseline characteristics                did endovascular treatment in patients with good-grade aneurysms,
                                                                                                                               but symptomatic vasospasm in patients with good-grade or poor-
                                                                                                                               grade aneurysms was unaffected by treatment type
  Bairstow,          All ruptured         10 Median GOS 1          12   Median GOS 2   None documented                         Endovascular treatment led to better functional outcome than did
  200220                                                                                                                       surgery
  Johnston,          All unruptured       62 92%               68       75%            None documented                         Endovascular treatment had higher rates of favourable outcomes
  200014                                                                                                                       than surgery in patients with unruptured aneurysms
  Raftopoulos, 59 ruptured and            64 87%               63       94%            Endovascular treatment was the first     Surgery led to better outcome than endovascular treatment
  200016       68 unruptured                                                           choice; surgery was used for patients
                                                                                       who could not be treated with
                                                                                       endovascular treatment
  Lot, 199917        280 ruptured        293 92%               102      85%            Endovascular treatment was the first     With appropriate selection of patients, endovascular treatment is a
                     and 115                                                           choice; surgery was used for patients   good alternative for treatment of aneurysms
                     unruptured                                                        who could not be treated with
                                                                                       endovascular treatment
  Gruber,            26 ruptured and     21     95%            20       75%            Endovascular group had worse            Endovascular treatment is an alternative to surgery in patients with
  199815             15 unruptured                                                     baseline characteristics                basilar artery apex aneurysms
  Kahara,            130 ruptured        44     91%            106      85%            Endovascular treatment was the first     Endovascular treatment is feasible, effective, and safe in small
  199918             and 20                                                            choice for unruptured aneurysms         aneurysms with a small neck
                     unruptured
  Gruber,            All ruptured        111    Mean GOS 2·3   45       Mean GOS 2·4   Endovascular group had worse            Delayed ischaemic neurological deficits are more common with
  199819                                                                               baseline characteristics                endovascular treatment than with surgery

 GOS=Glasgow outcome scale. The definition of good outcome varied between studies.

 Table 1: Characteristics and outcomes of surgical and endovascular treatments in 12 single-centre studies



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Multicentre studies with independent outcome                      respectively. At 12 months, good or moderate recovery on
ascertainment                                                     the Glasgow outcome scale was observed in 79% of
Rates of periprocedural morbidity and mortality for either        patients after endovascular treatment and 75% of patients
treatment were higher in multicentre observational                after surgery (p=0·3). Neuropsychiatric tests at 3 and
studies with independent assessment of outcome than in            12 months did not reveal any differences between the
self-reported studies14–25 (table 1); this indicates that study   groups. Crossover from endovascular to surgical
design can lead to reporting bias. Independently assessed         treatment (n=12) was greater than crossover from surgical
multicentre studies also suggest that the higher rates of         to endovascular treatment (n=4; p=0·03). No rebleedings
retreatment after endovascular treatment do not have an           occurred after the first hospitalisation. There was no
effect on outcome. For example, in ISUIA,11 in which               difference in cumulative survival times between the
endpoints were adjudicated by a central committee,                endovascular (mean survival time 1575 days, 95% CI
periprocedural morbidity and mortality was 12% for 1917           1403–1746) and surgical (1572 days, 1400–1745) treatment
patients who underwent surgery and 10% for 451 patients           groups (p=0·9). In MRI at 12 months after intervention,
who underwent endovascular treatments. However, these             superficial brain retraction deficits (p<0·001) and
results should be interpreted with the understanding that         ischaemic lesions in the territory of the ruptured
ISUIA was not designed for comparison of treatment                aneurysm (p=0·025) were more frequent in patients
modalities, and patients who received endovascular                treated with surgery than in those who received
treatment were at a higher risk of morbidity and mortality        endovascular treatment.
than those who received surgery, because of greater                 The randomised, multicentre phase III International
patient age, greater aneurysm size, and more aneurysms            Subarachnoid Aneurysm Trial (ISAT)32 compared the
in the posterior circulation. Importantly, patient age did        efficacy of endovascular treatment with that of surgery in
not affect outcome after endovascular treatment to the             patients with ruptured aneurysms who were suitable for
same extent as it did after surgery.                              either treatment. The aim was to determine whether
  In an ambidirectional cohort study,29 all patients with         endovascular treatment could reduce the rate of death or
ruptured intracranial aneurysms at nine institutions that         disability (defined as mRS 3–6) by 25% or more at 1 year
had expertise in endovascular and surgical treatment              in patients with ruptured intracranial aneurysms for
were followed up for early and delayed (>1 year) rerupture        whom both endovascular and surgical treatments were
and retreatment. 2·7% of the 299 endovascular-treated             acceptable options. A total of 1070 and 1073 patients were
patients and 1·0% of the 711 surgery-treated patients had         randomly assigned to surgical and endovascular
rebleeding during the first month after treatment. After           treatments, respectively. Recruitment was prematurely
1 year, the yearly rate of rebleeding of the index aneurysm       stopped after a planned interim analysis showed reduced
was low in both treatment groups: 0·1% after endovascular         disability in the endovascular treatment group. The
treatment (904 person-years of follow-up) and 0% after            proportion of patients who were dependent or dead at
surgery (2666 person-years). Retreatment after 1 year was         1 year was lower in those allocated to endovascular
more frequent after endovascular treatment, but major             treatment (24% of 801) than in those allocated to surgery
complications during this retreatment were rare. The              (31% of 793) (relative reduction in risk of dependency or
investigators concluded that the low rates of late                death was 23% [95% CI 9–34]; absolute risk reduction
rebleeding and periprocedural complications associated            was 7% [3–11]). However, the requirement for a second
with retreatment mean that the benefits of the procedures          procedure was higher after endovascular than after
are unlikely to differ after 1 year.                               surgical treatment. The risk of rebleeding from the
                                                                  ruptured aneurysm after 1 year was two per 1276 patient-
Randomised comparisons                                            years and zero per 1081 patient-years for patients allocated
A prospective randomised trial30,31 compared endovascular         to endovascular and surgical treatments, respectively.
and surgical treatment of intracranial aneurysms within             ISAT32,33 assessed survival and long-term outcome by
72 h of subarachnoid haemorrhage. The study assessed              reviewing the certified causes of death, case record
the angiographic outcome and clinical outcome                     forms, clinical records, and post-mortem details, if
(including neuropsychiatric evaluation) at 3 and                  available, supplemented at 1 year and yearly thereafter
12 months in 109 patients who were suitable for both              with a questionnaire mailed to surviving patients. The
endovascular and surgical treatment. Angiographic                 early survival advantage with endovascular treatment
outcomes in patients with aneurysms in the anterior               was maintained for up to 7 years (log-rank p=0·03). The
cerebral artery were significantly better after surgery than       risk of epilepsy was substantially lower with
after endovascular treatment, whereas those in patients           endovascular treatment than with surgery, but the risk
with aneurysms in the posterior circulation were                  of rebleeding after 1 year was non-significantly higher:
significantly better after endovascular treatment than             of nine patients who had confirmed rebleeding from
after surgery. One patient had early rebleeding after             the target aneurysm, seven had been allocated
endovascular treatment. Technique-related mortality was           endovascular treatment and two had been allocated
2% and 4% in the endovascular and surgical groups,                surgery. Follow-up of the ISAT patients34 showed that


http://neurology.thelancet.com Vol 6 September 2007                                                                                       819
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               191 of 1096 (17·4%) patients were retreated after           treatment in ISAT. There were no differences in the total
               endovascular treatment and 39 of 1012 patients (3·8%)       cost of treatment between the endovascular-treated
               were retreated after surgery. The rate of follow-up         (n=30) and the surgery-treated (n=32) patients: the
               angiography was higher in the endovascular-treated          benefits of shorter hospital stays for the endovascular-
               patients than in surgery-treated patients; this might in    treated patients were offset by higher procedure costs.
               part have increased the rate of detection of asymptomatic   There were no differences in clinical outcomes between
               aneurysm regrowth, and subsequently retreatment             the groups at 2 months and at 1 year.
               (88% vs 46%, respectively). 87 patients were retreated in      Cost-utility analysis37—in which benefits of an
               the absence of rebleeding 3 months after their initial      intervention are quantified in terms of quality-adjusted
               endovascular treatment. Although retreatment was 6·9        life-years (QALYs)—has become the standard analysis of
               times more likely after endovascular treatment than         cost-effectiveness. An incremental cost-effectiveness of
               after surgery, no permanent complications were              below US$20 000 per additional QALY is exceptionally
               reported with the retreatment. The mean time to             beneficial, values of $20 000–40 000 are acceptable, and
               retreatment was 21 months after endovascular treatment      values greater than $100 000 are not desirable. Most
               and 6 months after surgery, suggesting that recurrences     currently accepted programmes have an incremental cost-
               occur after longer periods in endovascular-treated          effectiveness of $60 000–100 000 per additional QALY.
               patients. This benefit of endovascular treatment on             In a cost-utility analysis, Johnston and colleagues38
               long-term survival was not offset by periprocedural          compared surgical and endovascular treatment with no
               complications, because occurrence of these was low for      treatment for unruptured aneurysms in a hypothetical
               retreatment.                                                cohort of 50-year-old women. For an asymptomatic
                 The effects of the two treatments on patient outcome       unruptured aneurysm less than 10 mm in diameter in
               were further compared in a meta-analysis35 of three         patients with no history of subarachnoid haemorrhage,
               randomised trials in 2272 patients with subarachnoid        both procedures resulted in a net loss in QALYs (surgery,
               haemorrhage. After 1 year of follow-up, the relative risk   loss of 1·6 QALY; endovascular treatment, loss of
               of poor outcome after endovascular treatment versus         0·6 QALY). For aneurysms of 10 mm diameter or larger,
               surgery was 0·76 (95% CI 0·67–0·88) and the absolute        treatment was cost-effective for aneurysms that produced
               risk reduction was 7% (4–11). For patients with an          symptoms by compressing neighbouring nerves and
               aneurysm in the anterior circulation, the relative risk     brain structures, and for patients with a history of
               of poor outcome after endovascular treatment versus         subarachnoid haemorrhage. Cost per additional QALY
               surgery was 0·78 (0·68–0·90) and the absolute risk          was $11 000–38 000 for surgery and $5000–42 000 for
               reduction was 7% (3–10). For patients with an aneurysm      endovascular treatment. The investigators concluded that
               in the posterior circulation, the relative risk was 0·41    both treatments are cost-effective for aneurysms that are
               (0·19–0·92) and the absolute decrease in risk was 27%       symptomatic or 10 mm in diameter or larger, and for
               (6–48). The investigators concluded that endovascular       patients with a history of subarachnoid haemorrhage.
               treatment is associated with a better outcome for              The higher cost of endovascular procedures might be
               patients who had ruptured aneurysms in either the           balanced by cost saved in reduced length of stay in
               anterior or posterior circulation and who were              hospital.20 However, the studies that support this idea
               otherwise in good health and considered suitable for        used short-term follow-up and do not take into account
               both surgical and endovascular treatment.                   other factors such as lost productivity of patients at work.
                                                                           Another important and unaddressed issue is how the
               Cost-effectiveness                                           cost-effectiveness of new and more expensive endo-
               As new and potentially more expensive technology is         vascular technology compares with that of older
               introduced, the difference in outcome should be assessed     endovascular techniques.
               against the difference in cost. Bairstow and colleagues20
               compared the cost and outcome of endovascular (n=10)        Quality of life and functional measures
               and surgical (n=12) treatments for ruptured intracranial    In a prospective multicentre observational study, Brilstra
               aneurysms. Despite incurring higher procedural costs        and colleagues39 measured the effect of surgical or
               than surgery, endovascular treatment was associated with    endovascular treatment of unruptured aneurysms on
               lower costs for staffing and the stay in hospital. This       functional health, quality of life, anxiety, and depression.
               study also reported that patients tended to return to       In the surgical group of 32 patients, 36 of all 37 aneurysms
               normal activity or paid employment sooner, and have a       (97%) were successfully treated and four patients (12%)
               more favourable functional outcome, after endovascular      had a permanent complication. At 3 months post-surgery,
               procedures than after surgery, although these findings       quality of life was worse than before treatment, and at
               were not included in the cost analysis.20 Javadpour and     12 months post-surgery the quality of life had improved
               colleagues36 compared the cost-effectiveness of surgery      but had not completely returned to baseline. In the
               with that of endovascular treatment for 62 patients         endovascular group of 19 patients, 16 of all 19 aneurysms
               randomly assigned to either surgery or endovascular         (84%) were occluded by 90% or more, and none of the


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surviving patients had complications with permanent           aneurysms unsuitable for endovascular treatment should
deficits. However, one patient died from rupture of an         be treated surgically if that option is judged to be viable
aneurysm previously treated by endovascular intervention.     by a vascular neurosurgeon.
Quality of life in the other 18 patients after 3 months and     The German Society of Neurosurgery44 stated that the
1 year was similar to that before treatment. Thus, in the     outcome after a specific treatment (surgical or
short term, surgical treatment, but not endovascular          endovascular) of ruptured intracranial aneurysms is
treatment, of patients with an unruptured aneurysm            determined by both the periprocedural complication rate
seems to have a negative effect on functional health and       and the success of preventing rebleeding from the treated
quality of life.                                              aneurysm. Endovascular treatment is a safe method
                                                              associated with fewer complications than surgery in
Recommendations from professional                             experienced hands. The success of complete obliteration
organisations                                                 is higher after surgery than after endovascular treatment,
There have been several sets of guidelines about              but whether incompletely occluded aneurysms have a
endovascular treatments for aneurysms since September         higher rate of rerupture, and therefore the definitive
1995, when the FDA approved Guglielmi detachable coils        long-term rerupture rate, is unknown.
for treatment of high-risk or inoperable ruptured and           Also in 2003, the UK National Institute for Health and
unruptured brain aneurysms.40 Panel 2 summarises the          Clinical Excellence (NICE)45 stated that endovascular
recommendations made in these guidelines, together with       treatment seems to be efficacious in obliteration of
recommendations made by published reports (table 2).          unruptured intracranial aneurysms and that the safety of
   In 1997, guidelines from the Canadian Neurosurgical        this treatment is similar to that of surgery. However, the
Society41 recommended early surgery for aneurysm              risks of treating unruptured intracranial aneurysms by any
treatment unless the aneurysm location or size makes          procedure might be greater than the yearly risk of rupture
this difficult. According to this report, aneurysm              without treatment. In the same year, NICE similarly stated46
obliteration is best accomplished with open microsurgery      that evidence on safety and efficacy lends support to use of
and clipping, although other options include proximal         endovascular treatment for ruptured intracranial
parent artery occlusion, trapping of the segment of the       aneurysms, provided that standard arrangements are used
artery that contains the aneurysm, and embolisation of        for consent, audit, and clinical governance.
the aneurysm using endovascular techniques. In 2000,            The Brain Attack Coalition47 recommended in 2005 that
the Stroke Council of the American Heart Association42        endovascular treatment of aneurysms is a safe and
recognised endovascular treatment as an option for            effective alternative to surgery in selected patients. These
unruptured intracranial aneurysms. However, although          guidelines also recommended that surgical and
the technique was being used with increasing frequency,       endovascular treatments should be done in a
the council decided that the efficacy of endovascular           comprehensive stroke centre, and that if a centre cannot
treatment for unruptured intracranial aneurysms should        offer these treatments, protocols should be developed for
not be judged until there had been a case-controlled,         the rapid transfer of patients to a facility that can.
randomised prospective trial.
  In 2002, the Committee on Cerebrovascular Imaging
of the American Heart Association Council on                    Panel 2: Guidelines for use of endovascular treatment
Cardiovascular Radiology7 recommended endovascular              Recommendations discussed in the main text and studies summarised in table 2 together
coils as a treatment option for ruptured and unruptured         suggest the following:
intracranial aneurysms. The council also suggested that         • Both endovascular and surgical treatment options must be available in any centre that
endovascular treatment should be used for patients in              treats patients with intracranial aneurysms
whom surgery is impossible or high risk, such as those          • There is evidence that endovascular treatment can be an initial treatment option for
with aneurysms in the posterior circulation. In 2003, the          all ruptured and unruptured intracranial aneurysms. However, only part of this
year in which the FDA approved Guglielmi detachable                evidence is derived from randomised trials, and further studies are needed
coils for use to treat all aneurysms, four reports further      • Endovascular treatment should be the preferred option only with the understanding
encouraged use of endovascular treatment. After the                that certain aneurysms are better treated with surgery. Physicians with endovascular
results of ISAT were published, the American Society of            expertise must also be familiar with the strengths of surgical treatment if they are to
Interventional and Therapeutic Neuroradiology and the              recommend the best treatment option
American Society of Neuroradiology43 recommended that           • Although significant emphasis has been placed on selecting the appropriate
endovascular therapy be considered for every patient with          endovascular or surgical treatment, conservative management might be the best option
a ruptured cerebral aneurysm, preferably following                 for some patients. Therefore, physicians involved in the care of patients with aneurysms
consultation with a neuroendovascular specialist. These            must understand the natural history of intracranial aneurysms in various settings
guidelines also proposed that the reasons for                   • Physicians and people who are responsible for institutions that treat aneurysms should
recommendation of one treatment over another should                think about cost-effectiveness before incorporating new and expensive technology
be documented, in accordance with the usual standards              into their practices
for informed consent, and that patients who have


http://neurology.thelancet.com Vol 6 September 2007                                                                                                      821
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                                   Implications of the comparisons of endovascular                                             haemorrhage in central Finland are candidates for
                                   and surgical treatments                                                                     aneurysm treatment.
                                   Implications for clinical practice
                                   On the basis of results from ISAT, we estimated that if a                                   Implications for patient outcomes
                                   new treatment for ruptured aneurysms had a 6% higher                                        To evaluate the effect of endovascular treatment on
                                   rate of discharge of patients home from hospital after                                      patient outcomes, we used data from the National
                                   subarachnoid haemorrhage than did an older procedure,                                       Hospital Discharge Survey to identify changes in
                                   use of the new procedure for 20% and 50% of patients                                        morbidity and mortality rates in adult patients who were
                                   with subarachnoid haemorrhage could lead to yearly                                          admitted to hospital for ruptured and unruptured
                                   savings of $11·4 million and $28·6 million, respectively                                    intracranial aneurysms.48 Variables pertaining to hospital
                                   (Qureshi AI, unpublished). However, the cost savings                                        admission were compared for three distinct time periods.
                                   and reduction in death and disability are obscured by the                                   In-hospital mortality rates for patients with subarachnoid
                                   relatively small proportion of patients with subarachnoid                                   haemorrhage demonstrated no significant change across
                                   haemorrhage who are considered for any aneurysm                                             the different periods (27·6%, 24·6%, and 26·3% in
                                   treatment. We have reported that a third of patients                                        1986–90, 1991–95, and 1996–2001, respectively), but rates
                                   admitted to hospital in the USA with subarachnoid                                           decreased across the three periods for patients with
                                   haemorrhage and half of those admitted with unruptured                                      unruptured intracranial aneurysms (5·9%, 6·3%, and
                                   intracranial aneurysms underwent either surgical or                                         1·4%, respectively; p=0·07).
                                   endovascular treatment.48 Cross and colleagues49 reported                                     A UK-based single-centre study51 investigated changes
                                   that 34% of 16 399 admissions for subarachnoid                                              in clinical therapy and outcome of 1609 patients with
                                   haemorrhage in 18 US states from 1998 to 2000 resulted                                      subarachnoid haemorrhage over 9 years (1990–98).
                                   in either surgical (29%) or endovascular (5%) treatment                                     Overall, 54% of patients (ranging from 35% to 66%) were
                                   for intracranial aneurysms. However, the proportion of                                      surgically treated, 8% had endovascular treatment
                                   patients eligible for such treatment is likely to be                                        (0·6%–18%), and 38% (28%–46%) were managed without
                                   higher—for example, Fogelholm and colleagues50                                              surgical treatment for the aneurysm. The proportion of
                                   estimated that about 60% of patients with subarachnoid                                      patients undergoing surgery decreased from 1994


                              Patients with ruptured intracranial aneurysms                                                        Patients with unruptured intracranial aneurysms
                              Candidates for any treatment*                     Candidates for either treatment†                   Candidates for any treatment*            Candidates for either treatment†
  Aneurysm obliteration       Higher with surgical treatment (SCS)17,18         Higher with surgical treatment (RCT)32             Higher with surgical treatment           ··
                                                                                                                                   (SCS)17,18
  Cerebral vasospasm          Higher with endovascular treatment (SCS)19        ··                                                 ··                                       ··
  Discharge outcome           Better with endovascular treatment (SCS)‡17 ··                                                       Better with endovascular treatment Better with endovascular treatment
                                                                                                                                   (MOS)26,27                         (SCS)14
  Hospital charges            No difference (SCS)20                              No difference (SCS)36                               Lower with endovascular treatment Lower with endovascular treatment
                                                                                                                                   (MOS)26,27                        (SCS)14
  2–6 month outcome           ··                                                Better with endovascular treatment                 ··                                       ··
                                                                                (RCT)32,33
  1-year outcome              ··                                                Better with endovascular treatment                 No difference (MOSI)11                    ··
                                                                                (RCT)32,33
  Neuropsychiatric            ··                                                No difference (RCT)30                               No difference (MOSI)11                    ··
  outcomes
  Perioperative and long- ··                                                    Lower with endovascular treatment (RCT)33          ··                                       ··
  term risk of seizures
  Quality of life (1-year     ··                                                ··                                                 Better with endovascular treatment ··
  outcomes)                                                                                                                        (MOS)39
  Early rebleeding§           ··                                                No difference (RCT)33                               ··                                       ··
  Late rebleeding             No difference (MOSI)29                             No difference (RCT)33                               ··                                       No difference (SCS)15
  Second treatment            Higher with endovascular treatment                Higher with endovascular treatment (RCT)34         ··                                       ··
                              (MOSI)29
  Late survival               ··                                                Better with endovascular treatment (RCT)33         ··                                       ··

 *Includes patients who were candidates for only surgical or only endovascular treatment. Endovascular treatment was preferentially used for patients with poor clinical and angiographic characteristics. †Patients
 for whom both endovascular and surgical treatments were acceptable options. ‡Not consistently demonstrated. §Rate of rebleeding was higher within 1 month after treatment in the endovascular-treated
 patients, but overall rate of rebleeding within 1 month was similar in the two groups because the rate of rebleeding was higher before the procedure in surgery-treated patients than in endovascular-treated
 patients. SCS=single-centre study. MOS=multicentre observational study. Double dots indicate that we found no relevant studies. MOSI=multicentre observational study with independent outcome
 ascertainment. RCT=randomised controlled trial.

 Table 2: Comparison of endovascular and surgical treatments



822                                                                                                                                                   http://neurology.thelancet.com Vol 6 September 2007
Review




onwards, owing to improvements in endovascular
treatment and higher rates of admission for patients with        Search strategy and selection criteria
poor-grade aneurysms. This change in admissions can              We based the review on personal knowledge of the subject
also explain an increase in mortality rate during the            supplemented by data from multicentre randomised trials,
period of review (from 18% to 32%).                              non-randomised controlled studies with independent
  The benefits of endovascular treatment are obscured in          outcome ascertainment, and selected observational studies.
patients with subarachnoid haemorrhage by preferential           The information was identified with multiple searches of
use of this treatment for patients with poor-grade               Medline from January, 1985, to May, 2007, by cross-
aneurysms, in whom outcome is predominantly                      referencing key words of “intracranial aneurysms”,
determined by initial clinical condition. Similarly,             “subarachnoid haemorrhage”, “embolization”, and
endovascular treatment has increased the proportion of           “detachable coils”. Only papers published in English were
elderly patients who are treated for ruptured aneurysms;         reviewed. We also reviewed abstracts from pertinent scientific
in these patients, short-term and long-term survival is          meetings, and information about technological developments
partly influenced by comorbidities, which limits the              was acquired through industrial resources available for clinical
overall benefit of aneurysm treatment. Nevertheless,              investigators.
endovascular treatment has greatly improved the overall
outcomes of patients with unruptured intracranial
aneurysms.                                                     to 31% following publication of the ISAT results, whereas
                                                               endovascular treatment of aneurysms increased from
Implications of ISAT                                           35% to 68%. During the same period, there was a non-
ISAT is to our knowledge the most comprehensive                significant improvement in outcome at 6 months and a
comparison of endovascular and surgical treatments.            decrease in the mean total duration of hospital stay,
However, results suggest that the patients treated in ISAT     which was related to the shorter duration of hospital stay
had more favourable baseline clinical and procedural           associated with endovascular treatment than with
characteristics than do patients with aneurysms treated        surgery. Another study55 analysed the therapeutic
outside this study. For example, a comparison of patients      decision-making process and outcome in 100 consecutive
admitted with subarachnoid haemorrhage to a nationally         patients with subarachnoid haemorrhage treated since
representative sample of hospitals in the USA48 showed         the publication of ISAT. 47 patients underwent surgery,
that the mean age of patients was lower in ISAT.32 In-         41 underwent endovascular treatment, and 12 received a
hospital mortality was also lower (6% overall in ISAT32 vs     combination of the two procedures. Good functional
26% for patients with subarachnoid haemorrhage in the          outcome (mRS 0–2) after 6 months was achieved in 71%
USA48). Similarly, the mortality in ISAT patients was          of patients. This result suggests that, in routine clinical
lower than that reported in the Japanese Standard Stroke       practice, excellent functional results can be seen when
Registry Study (22%).52                                        surgical and endovascular treatments are assigned on the
  Despite this difference, results from another study           basis of data from ISAT.
suggest that ISAT can be applied to the general
population. Flett and colleagues53 reported on patients        Conclusions
who were admitted to one centre that participated in           Endovascular treatment has been incorporated into the
ISAT but who were not recruited into the trial (72% of all     treatment of patients with subarachnoid haemorrhage
admissions to the centre; most exclusions from ISAT            who are poor candidates for surgical treatment. Since the
were because one treatment was judged to be preferable         emergence of endovascular treatments, reports such as
to the other by the treating physicians, on the basis of       ISAT have supported the idea that endovascular treatment
morphology and location of the aneurysm or clinical            is a valid alternative for many patients (table 2). However,
characteristics of the patient). Nine of these patients were   the definition of these patients is arbitrary, and the
treated conservatively, 67 underwent surgical treatment,       decision to use endovascular treatment for unruptured
and 46 underwent endovascular treatment. At 12 months,         intracranial aneurysms can depend on the views and
72% of the patients who received endovascular treatment        expertise in local institutions. A better understanding of
and 49% of those who received surgery had a good mRS           the long-term risk of rupture, periprocedural results, and
(0–2). This higher rate of favourable outcomes in patients     complications associated with available procedures is
who received endovascular treatment than in those who          helping to clarify whether therapeutic intervention is
received surgery provides evidence that the results of         beneficial for unruptured intracranial aneurysms. Future
ISAT can be applied generally.                                 research priorities include a comparison of treatments for
  The proportion of patients undergoing endovascular           unruptured intracranial aneurysms that can be treated by
treatment has increased since the publication of ISAT. In      either surgical or endovascular treatment, and a
a report from a single neurosurgical unit in the UK,54 the     comparison of treatments for ruptured intracranial
proportion of patients with subarachnoid haemorrhage           aneurysms in patient populations not included in ISAT,
who underwent surgical treatment decreased from 51%            with use of randomised clinical trials and prospective


http://neurology.thelancet.com Vol 6 September 2007                                                                                          823
Review




               multicentre registries with independent outcome                              19   Gruber A, Ungersbock K, Reinprecht A, et al. Evaluation of
               ascertainment. As physicians, we should use data to guide                         cerebral vasospasm after early surgical and endovascular
                                                                                                 treatment of ruptured intracranial aneurysms. Neurosurgery 1998;
               our decisions on a case-by-case basis, and we should                              42: 258–67.
               remember that selection of appropriate patients for each                     20   Bairstow P, Dodgson A, Linto J, Khangure M. Comparison of cost
               therapeutic method can improve the overall results.                               and outcome of endovascular and neurosurgical procedures in the
                                                                                                 treatment of ruptured intracranial aneurysms.
               Contributors                                                                      Australas Radiol 2002; 46: 249–51.
               All authors contributed equally to the literature search, writing, and       21   Kato Y, Sano H, Dong PT, et al. The effect of clipping and coiling in
               revision of the manuscript. All authors have seen and approved the final           acute severe subarachnoid hemorrhage after international
               version.                                                                          subarachnoid aneurysmal trial (ISAT) results.
                                                                                                 Minim Invasive Neurosurg 2005; 48: 224–27.
               Conflicts of interest
                                                                                            22   Taha MM, Nakahara I, Higashi T, et al. Endovascular embolization
               We have no conflicts of interest.                                                  vs surgical clipping in treatment of cerebral aneurysms: morbidity
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http://neurology.thelancet.com Vol 6 September 2007                                                                                                               825

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Comparison of endovascular and surgical treatments for intracranial aneurysms

  • 1. Review Comparison of endovascular and surgical treatments for intracranial aneurysms: an evidence-based review Adnan I Qureshi, Vallabh Janardhan, Ricardo A Hanel, Giuseppe Lanzino Lancet Neurol 2007; 6: 816–25 Intracranial aneurysms can be treated with endovascular or surgical techniques. We provide an objective comparison Zeenat Qureshi Stroke Research of these treatments, using data from single-centre studies, multicentre studies with and without independent outcome Center, Department of ascertainment, and randomised clinical trials. We compared the outcomes of patients who were candidates for Neurology, University of endovascular treatment, surgical treatment, or both. In patients with ruptured intracranial aneurysms, rates of Minnesota, Minneapolis, MN, USA (A I Qureshi MD, aneurysm obliteration were higher, and need for second treatment was lower, after surgery than after endovascular V Janardhan MD); Division of treatment. However, in observational studies and randomised trials, outcome at discharge, at 2–6 months, and at Neurological Surgery, Barrow 1 year, and later survival, were all better after endovascular treatment than after surgery. The results suggest that the Neurological Institute, higher rates of incomplete obliteration and retreatment after endovascular treatment do not affect patients’ clinical St Joseph’s Hospital and Medical Center, Phoenix, AZ, outcome. In observational studies of patients with unruptured intracranial aneurysms, discharge outcomes were USA (R A Hanel MD); and better and hospital costs were lower after endovascular treatment than after surgery. These patients showed no Department of Neurosurgery, difference between the two treatments in 1-year outcomes and later rebleeding, although few data were available for Illinois Neurological Institute, University of Illinois College of this comparison. Medicine, Peoria, IL, USA (G Lanzino MD) Introduction such as detachable coils and intravascular stents. However, Correspondence to: Intracranial aneurysms are focal dilatations in medium- the use of these treatments varies considerably among Adnan I Qureshi, Department of sized arteries. They are a substantial health problem, and institutions and practitioners. National organisations and Neurology, University Of affect roughly 2% of the population worldwide.1 In 1937, medical institutions are trying to ensure that the new Minnesota, 12-100 Phillips Wangensteen Building, MMC Walter Dandy performed the first surgical treatment of technology is adapted in a uniform and evidence-based 295, 420 Delaware Street SE an aneurysm using a vascular clip designed by Harvey way. Over the past 5 years, as endovascular treatments have Minneapolis, MN 55455, USA Cushing.2,3 Subsequent advances in neurosurgical become more widely available, practitioners have been aiqureshi@hotmail.com techniques (eg, the development of operating constantly seeking comprehensive and objective sources microscopes, microsurgical instruments, improved clips, of information to help them select patients for a particular neuroanaesthesia, and perioperative management for treatment. In this article, we review: comparisons of complications such as hydrocephalus and symptomatic endovascular treatment with surgery; how evidence is vasospasm) enabled neurosurgeons to treat most cerebral being incorporated into professional guidelines; and aneurysms, and surgery was the predominant treatment implications for the future, including deficiencies in some for almost four decades. Attempts were made to place of the present data. Panel 1 shows how we have classified iron particles, detachable balloons, and platinum coils surgical and endovascular treatments. into intracranial aneurysms through endovascular routes1 but, although such treatment was successful in some Pathophysiology and rates of aneurysm rupture patients, its applicability was limited by high rates of Intracranial aneurysms result from degeneration of the particle migration, balloon deflation, and aneurysm arterial wall, which is caused by congenital and acquired rupture. In the late 1980s, Guglielmi and colleagues4 medical defects8 and factors such as hypertension and developed a device in which a soft platinum coil soldered cigarette smoking.9,10 Enlargement and rupture of onto a stainless steel wire was successfully delivered aneurysms results from interplay between continuing through a microcatheter into the aneurysm sac—the coil degeneration and haemodynamics. A major rupture can mass protected against rupture by buffering the be preceded by infiltration of the artery wall by fibrin and haemodynamic stress against the fundus of the leucocytes, bleb formation, and a minor haemorrhage.9,10 aneurysm.5,6 The development and subsequent approval Some intracranial aneurysms rupture early in their of such detachable coils by the US Food and Drug development and are commonly detected as small Administration (FDA) in 1995 mandated a reassessment ruptured aneurysms (aneurysms that show early of intracranial aneurysm treatment. vulnerability); others rupture late in their development Initially, endovascular treatment was used in patients and are commonly detected in the unruptured stage, who were thought to be poor candidates for surgical rupturing only after growing to a critical size (aneurysms treatment,1,7 such as people who: had severe neurological that show late vulnerability). The factors that cause deficits; had an aneurysm in the posterior circulation or in aneurysms to have early rather than late vulnerability are the cavernous segment of internal carotid artery; were aged unclear. 75 years or over; presented 3–10 days after aneurysm The rupture rate of aneurysms varies with location, as rupture; or had active cerebral vasospasm. Over the past reported by the International Study of Unruptured decade, treatment of intracranial aneurysms has evolved Intracranial Aneurysms (ISUIA), which investigated rapidly, with new developments in endovascular treatments 2686 unruptured, untreated intracranial aneurysms in 816 http://neurology.thelancet.com Vol 6 September 2007
  • 2. Review 1692 patients (mean follow-up 4·1 years).11 Patients who did not have a history of subarachnoid haemorrhage who Panel 1: Variations of surgical and endovascular treatments for intracranial aneurysms had aneurysms in the anterior circulation (ie, in the Surgical treatments internal carotid artery, anterior communicating or Direct clipping (clips vary in strength, shape, and size) anterior cerebral artery, or middle cerebral artery) had Direct clipping with decompression of the aneurysmal sac (can include thrombectomy) cumulative 5-year rupture rates of 0%, 2·6%, 14·5%, and Direct clipping with neuroprotection (barbiturate anaesthesia or hypothermia) 40% for aneurysms of less than 7 mm, 7–12 mm, Proximal ligation (abrupt or gradual) or trapping with or without use of bypass 13–24 mm, and 25 mm or greater, respectively. Rupture Wrapping or coating rates for aneurysms of the same sizes in the posterior Direct clipping of remnant aneurysm following endovascular treatment circulation and posterior communicating artery were 2·5%, 14·5%, 18·4%, and 50%, respectively. Patients Endovascular treatments with a history of subarachnoid haemorrhage had a 5-year Detachable coil placements (coils vary in strength, shape, and size) cumulative rupture rate of 1·5% for aneurysms of less Detachable coil placements with temporary balloon assistance than 7 mm in the anterior circulation, compared with Detachable coils and intravascular stent placement 3·4% for aneurysms of the same size in the posterior Liquid embolic agent injection with intravascular balloon or stent assistance circulation and posterior communicating artery. The Occlusion of parent vessel reason for the different rates of rupture between the Detachable coil placements in remnant aneurysm following surgical treatment anterior and posterior circulation is unclear. There are few data on the risk of rupture 5 years after and associated outcomes in various settings. However, detection of an unruptured aneurysm. Juvela and the comparative value of these studies is limited by colleagues12 followed 142 patients with 181 unruptured prominent heterogeneity in selection of patients and aneurysms for a median period of 20 years (range 1–39 imbalances in baseline characteristics between the two years). Six patients had a single symptomatic aneurysm, treatment groups. Some single-centre studies have five had a single incidentally discovered aneurysm, and reported higher rates of incomplete obliteration with 131 had a history of rupture and subsequent treatment of endovascular treatment than with surgery,16,17 although another intracranial aneurysm. During 2575 person- the effect of incomplete obliteration on overall outcome years of follow-up, there were 33 first-time episodes of was small, and there was no difference in risk of early haemorrhage from previously unruptured aneurysms, rebleeding between the treatment groups.15,17 Studies that with an average yearly incidence of 1·3%. The cumulative reported better outcomes with surgery also reported rate of rupture among these 142 patients was 10·5% at more unfavourable baseline characteristics in patients 10 years, and 30·3% at 30 years. who received endovascular treatment.21,22 Conversely, in Following rupture of an intracranial aneurysm, studies that used endovascular treatment as the first recurrent rupture and subarachnoid haemorrhage occur choice,16,17 many patients who were considered unsuitable with much higher frequency. For example, Jane and for endovascular treatment subsequently underwent colleagues13 reported that the rate of rebleeding among surgery. patients with ruptured aneurysms was 50% within the Johnston and colleagues14 reduced the effects of these first 6 months and 3% per year thereafter. The goal of imbalances between baseline characteristics using a obliterative treatment is to prevent primary subarachnoid blinded comparison of patients with unruptured haemorrhage in patients with unruptured aneurysms, intracranial aneurysms who received surgical (n=68) or and recurrent subarachnoid haemorrhage in patients endovascular (n=62) treatment. All 130 aneurysms were with ruptured aneurysms. judged by a panel of neurosurgeons and neuro- interventional radiologists to be treatable by either Comparisons of endovascular and surgical surgery or endovascular treatment. A higher frequency treatments of post-procedural disability (score on the modified Single-centre comparisons Rankin scale [mRS] ≥2) was reported in patients who An important point to note before we compare treatments underwent surgery compared with those who underwent for intracranial aneurysms is that some patients are endovascular treatment (25% vs 8%). The length of stay candidates for surgery only or endovascular treatment in hospital, number of days in intensive care, and hospital only, whereas for other patients, either treatment is an costs were all greater for surgical patients. There were acceptable option. This distinction depends on the three delayed subarachnoid or intracranial haemorrhages clinical condition of the patient, the morphology and in the endovascular group and one in the surgical group location of the aneurysm, and institutional expertise. after follow-up of 3·9 years per patient. Single-centre studies of endovascular and surgical treatments14–25 (table 1) are valuable because the overall Multicentre comparisons treated population and periprocedural care do not vary Observational studies that use multicentre databases within each study. These studies thus provide an estimate show consistently lower rates of in-hospital death and of the proportion of patients treated with each modality disability after endovascular treatment than after http://neurology.thelancet.com Vol 6 September 2007 817
  • 3. Review surgery.26,27 One procedure cannot be said to be better Adverse outcomes (in-hospital death, or discharge to a than another without knowledge of the baseline nursing home or rehabilitation hospital) were more characteristics that affect outcome, but, as reported in frequent in the 1669 patients treated with surgery (25%) the single-centre studies, shorter hospital stays and than in the 400 who received endovascular therapy lower hospital costs lend support to the use of (10%). In-hospital death was more frequent after endovascular treatment in selected patients. Johnston surgery than after endovascular treatment (3·5% vs and colleagues26 compared complications of surgical and 0·5%), and length of stay and hospital costs were endovascular treatment for unruptured intracranial greater after surgery. During the study period, adverse aneurysms at 60 hospitals in the US University Health outcomes declined for endovascular therapy (26% in System Consortium between 1994 and 1997. Adverse 1991 vs 4% in 1998) but not for surgery (26% in 1991 vs outcomes, defined as in-hospital death or transfer to a 21% in 1998). nursing home or rehabilitation hospital, were more Berman and colleagues28 evaluated the effect of common in 2357 patients who underwent surgery (19%) hospital characteristics on outcome in 2200 patients than in 255 who received endovascular treatment (11%). with ruptured cerebral aneurysms and 3763 patients In-hospital mortality was higher in surgical patients with unruptured aneurysms treated in New York state, (2·3% vs 0·4%) but there was no difference in the USA, from 1995 to 2000. More frequent use of multivariate analysis. Lengths of stay and hospital costs endovascular treatment in a hospital was associated were greater for surgical patients after adjustment for with fewer adverse outcomes (death or discharge to a confounding factors. rehabilitation hospital or long-term facility). Hospital Johnston and co-workers27 reviewed 2069 patients procedural volume and the propensity to use with unruptured intracranial aneurysms using a state- endovascular treatment were both independently wide database of hospital discharges in California, USA. associated with a good outcome. Aneurysm Endovascular Surgery Imbalance between treatment Conclusion characteristics treatment groups n Good outcome n Good outcome Kaku, 2007 24 79 ruptured 47 81% 32 78% None documented A team of experts in microsurgery and endovascular treatment should assess each aneurysm Helland, All ruptured 83 66% 203 48% None documented Endovascular treatment led to better clinical outcome than did 200625 surgery Taha, 200622 53 ruptured and 71 80% 62 66% Endovascular group had worse Endovascular treatment is a safe alternative to surgery for both 80 unruptured baseline characteristics ruptured and unruptured aneurysms. Kato, 200521 All ruptured 59 44% 120 69% Endovascular group had worse Surgery led to better outcome than did endovascular treatment in baseline characteristics patients with poor-grade aneurysms Hoh, 200423 All ruptured 102 33% 413 55% Endovascular group had worse Surgery led to better outcome and lower mortality at discharge than baseline characteristics did endovascular treatment in patients with good-grade aneurysms, but symptomatic vasospasm in patients with good-grade or poor- grade aneurysms was unaffected by treatment type Bairstow, All ruptured 10 Median GOS 1 12 Median GOS 2 None documented Endovascular treatment led to better functional outcome than did 200220 surgery Johnston, All unruptured 62 92% 68 75% None documented Endovascular treatment had higher rates of favourable outcomes 200014 than surgery in patients with unruptured aneurysms Raftopoulos, 59 ruptured and 64 87% 63 94% Endovascular treatment was the first Surgery led to better outcome than endovascular treatment 200016 68 unruptured choice; surgery was used for patients who could not be treated with endovascular treatment Lot, 199917 280 ruptured 293 92% 102 85% Endovascular treatment was the first With appropriate selection of patients, endovascular treatment is a and 115 choice; surgery was used for patients good alternative for treatment of aneurysms unruptured who could not be treated with endovascular treatment Gruber, 26 ruptured and 21 95% 20 75% Endovascular group had worse Endovascular treatment is an alternative to surgery in patients with 199815 15 unruptured baseline characteristics basilar artery apex aneurysms Kahara, 130 ruptured 44 91% 106 85% Endovascular treatment was the first Endovascular treatment is feasible, effective, and safe in small 199918 and 20 choice for unruptured aneurysms aneurysms with a small neck unruptured Gruber, All ruptured 111 Mean GOS 2·3 45 Mean GOS 2·4 Endovascular group had worse Delayed ischaemic neurological deficits are more common with 199819 baseline characteristics endovascular treatment than with surgery GOS=Glasgow outcome scale. The definition of good outcome varied between studies. Table 1: Characteristics and outcomes of surgical and endovascular treatments in 12 single-centre studies 818 http://neurology.thelancet.com Vol 6 September 2007
  • 4. Review Multicentre studies with independent outcome respectively. At 12 months, good or moderate recovery on ascertainment the Glasgow outcome scale was observed in 79% of Rates of periprocedural morbidity and mortality for either patients after endovascular treatment and 75% of patients treatment were higher in multicentre observational after surgery (p=0·3). Neuropsychiatric tests at 3 and studies with independent assessment of outcome than in 12 months did not reveal any differences between the self-reported studies14–25 (table 1); this indicates that study groups. Crossover from endovascular to surgical design can lead to reporting bias. Independently assessed treatment (n=12) was greater than crossover from surgical multicentre studies also suggest that the higher rates of to endovascular treatment (n=4; p=0·03). No rebleedings retreatment after endovascular treatment do not have an occurred after the first hospitalisation. There was no effect on outcome. For example, in ISUIA,11 in which difference in cumulative survival times between the endpoints were adjudicated by a central committee, endovascular (mean survival time 1575 days, 95% CI periprocedural morbidity and mortality was 12% for 1917 1403–1746) and surgical (1572 days, 1400–1745) treatment patients who underwent surgery and 10% for 451 patients groups (p=0·9). In MRI at 12 months after intervention, who underwent endovascular treatments. However, these superficial brain retraction deficits (p<0·001) and results should be interpreted with the understanding that ischaemic lesions in the territory of the ruptured ISUIA was not designed for comparison of treatment aneurysm (p=0·025) were more frequent in patients modalities, and patients who received endovascular treated with surgery than in those who received treatment were at a higher risk of morbidity and mortality endovascular treatment. than those who received surgery, because of greater The randomised, multicentre phase III International patient age, greater aneurysm size, and more aneurysms Subarachnoid Aneurysm Trial (ISAT)32 compared the in the posterior circulation. Importantly, patient age did efficacy of endovascular treatment with that of surgery in not affect outcome after endovascular treatment to the patients with ruptured aneurysms who were suitable for same extent as it did after surgery. either treatment. The aim was to determine whether In an ambidirectional cohort study,29 all patients with endovascular treatment could reduce the rate of death or ruptured intracranial aneurysms at nine institutions that disability (defined as mRS 3–6) by 25% or more at 1 year had expertise in endovascular and surgical treatment in patients with ruptured intracranial aneurysms for were followed up for early and delayed (>1 year) rerupture whom both endovascular and surgical treatments were and retreatment. 2·7% of the 299 endovascular-treated acceptable options. A total of 1070 and 1073 patients were patients and 1·0% of the 711 surgery-treated patients had randomly assigned to surgical and endovascular rebleeding during the first month after treatment. After treatments, respectively. Recruitment was prematurely 1 year, the yearly rate of rebleeding of the index aneurysm stopped after a planned interim analysis showed reduced was low in both treatment groups: 0·1% after endovascular disability in the endovascular treatment group. The treatment (904 person-years of follow-up) and 0% after proportion of patients who were dependent or dead at surgery (2666 person-years). Retreatment after 1 year was 1 year was lower in those allocated to endovascular more frequent after endovascular treatment, but major treatment (24% of 801) than in those allocated to surgery complications during this retreatment were rare. The (31% of 793) (relative reduction in risk of dependency or investigators concluded that the low rates of late death was 23% [95% CI 9–34]; absolute risk reduction rebleeding and periprocedural complications associated was 7% [3–11]). However, the requirement for a second with retreatment mean that the benefits of the procedures procedure was higher after endovascular than after are unlikely to differ after 1 year. surgical treatment. The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 patient- Randomised comparisons years and zero per 1081 patient-years for patients allocated A prospective randomised trial30,31 compared endovascular to endovascular and surgical treatments, respectively. and surgical treatment of intracranial aneurysms within ISAT32,33 assessed survival and long-term outcome by 72 h of subarachnoid haemorrhage. The study assessed reviewing the certified causes of death, case record the angiographic outcome and clinical outcome forms, clinical records, and post-mortem details, if (including neuropsychiatric evaluation) at 3 and available, supplemented at 1 year and yearly thereafter 12 months in 109 patients who were suitable for both with a questionnaire mailed to surviving patients. The endovascular and surgical treatment. Angiographic early survival advantage with endovascular treatment outcomes in patients with aneurysms in the anterior was maintained for up to 7 years (log-rank p=0·03). The cerebral artery were significantly better after surgery than risk of epilepsy was substantially lower with after endovascular treatment, whereas those in patients endovascular treatment than with surgery, but the risk with aneurysms in the posterior circulation were of rebleeding after 1 year was non-significantly higher: significantly better after endovascular treatment than of nine patients who had confirmed rebleeding from after surgery. One patient had early rebleeding after the target aneurysm, seven had been allocated endovascular treatment. Technique-related mortality was endovascular treatment and two had been allocated 2% and 4% in the endovascular and surgical groups, surgery. Follow-up of the ISAT patients34 showed that http://neurology.thelancet.com Vol 6 September 2007 819
  • 5. Review 191 of 1096 (17·4%) patients were retreated after treatment in ISAT. There were no differences in the total endovascular treatment and 39 of 1012 patients (3·8%) cost of treatment between the endovascular-treated were retreated after surgery. The rate of follow-up (n=30) and the surgery-treated (n=32) patients: the angiography was higher in the endovascular-treated benefits of shorter hospital stays for the endovascular- patients than in surgery-treated patients; this might in treated patients were offset by higher procedure costs. part have increased the rate of detection of asymptomatic There were no differences in clinical outcomes between aneurysm regrowth, and subsequently retreatment the groups at 2 months and at 1 year. (88% vs 46%, respectively). 87 patients were retreated in Cost-utility analysis37—in which benefits of an the absence of rebleeding 3 months after their initial intervention are quantified in terms of quality-adjusted endovascular treatment. Although retreatment was 6·9 life-years (QALYs)—has become the standard analysis of times more likely after endovascular treatment than cost-effectiveness. An incremental cost-effectiveness of after surgery, no permanent complications were below US$20 000 per additional QALY is exceptionally reported with the retreatment. The mean time to beneficial, values of $20 000–40 000 are acceptable, and retreatment was 21 months after endovascular treatment values greater than $100 000 are not desirable. Most and 6 months after surgery, suggesting that recurrences currently accepted programmes have an incremental cost- occur after longer periods in endovascular-treated effectiveness of $60 000–100 000 per additional QALY. patients. This benefit of endovascular treatment on In a cost-utility analysis, Johnston and colleagues38 long-term survival was not offset by periprocedural compared surgical and endovascular treatment with no complications, because occurrence of these was low for treatment for unruptured aneurysms in a hypothetical retreatment. cohort of 50-year-old women. For an asymptomatic The effects of the two treatments on patient outcome unruptured aneurysm less than 10 mm in diameter in were further compared in a meta-analysis35 of three patients with no history of subarachnoid haemorrhage, randomised trials in 2272 patients with subarachnoid both procedures resulted in a net loss in QALYs (surgery, haemorrhage. After 1 year of follow-up, the relative risk loss of 1·6 QALY; endovascular treatment, loss of of poor outcome after endovascular treatment versus 0·6 QALY). For aneurysms of 10 mm diameter or larger, surgery was 0·76 (95% CI 0·67–0·88) and the absolute treatment was cost-effective for aneurysms that produced risk reduction was 7% (4–11). For patients with an symptoms by compressing neighbouring nerves and aneurysm in the anterior circulation, the relative risk brain structures, and for patients with a history of of poor outcome after endovascular treatment versus subarachnoid haemorrhage. Cost per additional QALY surgery was 0·78 (0·68–0·90) and the absolute risk was $11 000–38 000 for surgery and $5000–42 000 for reduction was 7% (3–10). For patients with an aneurysm endovascular treatment. The investigators concluded that in the posterior circulation, the relative risk was 0·41 both treatments are cost-effective for aneurysms that are (0·19–0·92) and the absolute decrease in risk was 27% symptomatic or 10 mm in diameter or larger, and for (6–48). The investigators concluded that endovascular patients with a history of subarachnoid haemorrhage. treatment is associated with a better outcome for The higher cost of endovascular procedures might be patients who had ruptured aneurysms in either the balanced by cost saved in reduced length of stay in anterior or posterior circulation and who were hospital.20 However, the studies that support this idea otherwise in good health and considered suitable for used short-term follow-up and do not take into account both surgical and endovascular treatment. other factors such as lost productivity of patients at work. Another important and unaddressed issue is how the Cost-effectiveness cost-effectiveness of new and more expensive endo- As new and potentially more expensive technology is vascular technology compares with that of older introduced, the difference in outcome should be assessed endovascular techniques. against the difference in cost. Bairstow and colleagues20 compared the cost and outcome of endovascular (n=10) Quality of life and functional measures and surgical (n=12) treatments for ruptured intracranial In a prospective multicentre observational study, Brilstra aneurysms. Despite incurring higher procedural costs and colleagues39 measured the effect of surgical or than surgery, endovascular treatment was associated with endovascular treatment of unruptured aneurysms on lower costs for staffing and the stay in hospital. This functional health, quality of life, anxiety, and depression. study also reported that patients tended to return to In the surgical group of 32 patients, 36 of all 37 aneurysms normal activity or paid employment sooner, and have a (97%) were successfully treated and four patients (12%) more favourable functional outcome, after endovascular had a permanent complication. At 3 months post-surgery, procedures than after surgery, although these findings quality of life was worse than before treatment, and at were not included in the cost analysis.20 Javadpour and 12 months post-surgery the quality of life had improved colleagues36 compared the cost-effectiveness of surgery but had not completely returned to baseline. In the with that of endovascular treatment for 62 patients endovascular group of 19 patients, 16 of all 19 aneurysms randomly assigned to either surgery or endovascular (84%) were occluded by 90% or more, and none of the 820 http://neurology.thelancet.com Vol 6 September 2007
  • 6. Review surviving patients had complications with permanent aneurysms unsuitable for endovascular treatment should deficits. However, one patient died from rupture of an be treated surgically if that option is judged to be viable aneurysm previously treated by endovascular intervention. by a vascular neurosurgeon. Quality of life in the other 18 patients after 3 months and The German Society of Neurosurgery44 stated that the 1 year was similar to that before treatment. Thus, in the outcome after a specific treatment (surgical or short term, surgical treatment, but not endovascular endovascular) of ruptured intracranial aneurysms is treatment, of patients with an unruptured aneurysm determined by both the periprocedural complication rate seems to have a negative effect on functional health and and the success of preventing rebleeding from the treated quality of life. aneurysm. Endovascular treatment is a safe method associated with fewer complications than surgery in Recommendations from professional experienced hands. The success of complete obliteration organisations is higher after surgery than after endovascular treatment, There have been several sets of guidelines about but whether incompletely occluded aneurysms have a endovascular treatments for aneurysms since September higher rate of rerupture, and therefore the definitive 1995, when the FDA approved Guglielmi detachable coils long-term rerupture rate, is unknown. for treatment of high-risk or inoperable ruptured and Also in 2003, the UK National Institute for Health and unruptured brain aneurysms.40 Panel 2 summarises the Clinical Excellence (NICE)45 stated that endovascular recommendations made in these guidelines, together with treatment seems to be efficacious in obliteration of recommendations made by published reports (table 2). unruptured intracranial aneurysms and that the safety of In 1997, guidelines from the Canadian Neurosurgical this treatment is similar to that of surgery. However, the Society41 recommended early surgery for aneurysm risks of treating unruptured intracranial aneurysms by any treatment unless the aneurysm location or size makes procedure might be greater than the yearly risk of rupture this difficult. According to this report, aneurysm without treatment. In the same year, NICE similarly stated46 obliteration is best accomplished with open microsurgery that evidence on safety and efficacy lends support to use of and clipping, although other options include proximal endovascular treatment for ruptured intracranial parent artery occlusion, trapping of the segment of the aneurysms, provided that standard arrangements are used artery that contains the aneurysm, and embolisation of for consent, audit, and clinical governance. the aneurysm using endovascular techniques. In 2000, The Brain Attack Coalition47 recommended in 2005 that the Stroke Council of the American Heart Association42 endovascular treatment of aneurysms is a safe and recognised endovascular treatment as an option for effective alternative to surgery in selected patients. These unruptured intracranial aneurysms. However, although guidelines also recommended that surgical and the technique was being used with increasing frequency, endovascular treatments should be done in a the council decided that the efficacy of endovascular comprehensive stroke centre, and that if a centre cannot treatment for unruptured intracranial aneurysms should offer these treatments, protocols should be developed for not be judged until there had been a case-controlled, the rapid transfer of patients to a facility that can. randomised prospective trial. In 2002, the Committee on Cerebrovascular Imaging of the American Heart Association Council on Panel 2: Guidelines for use of endovascular treatment Cardiovascular Radiology7 recommended endovascular Recommendations discussed in the main text and studies summarised in table 2 together coils as a treatment option for ruptured and unruptured suggest the following: intracranial aneurysms. The council also suggested that • Both endovascular and surgical treatment options must be available in any centre that endovascular treatment should be used for patients in treats patients with intracranial aneurysms whom surgery is impossible or high risk, such as those • There is evidence that endovascular treatment can be an initial treatment option for with aneurysms in the posterior circulation. In 2003, the all ruptured and unruptured intracranial aneurysms. However, only part of this year in which the FDA approved Guglielmi detachable evidence is derived from randomised trials, and further studies are needed coils for use to treat all aneurysms, four reports further • Endovascular treatment should be the preferred option only with the understanding encouraged use of endovascular treatment. After the that certain aneurysms are better treated with surgery. Physicians with endovascular results of ISAT were published, the American Society of expertise must also be familiar with the strengths of surgical treatment if they are to Interventional and Therapeutic Neuroradiology and the recommend the best treatment option American Society of Neuroradiology43 recommended that • Although significant emphasis has been placed on selecting the appropriate endovascular therapy be considered for every patient with endovascular or surgical treatment, conservative management might be the best option a ruptured cerebral aneurysm, preferably following for some patients. Therefore, physicians involved in the care of patients with aneurysms consultation with a neuroendovascular specialist. These must understand the natural history of intracranial aneurysms in various settings guidelines also proposed that the reasons for • Physicians and people who are responsible for institutions that treat aneurysms should recommendation of one treatment over another should think about cost-effectiveness before incorporating new and expensive technology be documented, in accordance with the usual standards into their practices for informed consent, and that patients who have http://neurology.thelancet.com Vol 6 September 2007 821
  • 7. Review Implications of the comparisons of endovascular haemorrhage in central Finland are candidates for and surgical treatments aneurysm treatment. Implications for clinical practice On the basis of results from ISAT, we estimated that if a Implications for patient outcomes new treatment for ruptured aneurysms had a 6% higher To evaluate the effect of endovascular treatment on rate of discharge of patients home from hospital after patient outcomes, we used data from the National subarachnoid haemorrhage than did an older procedure, Hospital Discharge Survey to identify changes in use of the new procedure for 20% and 50% of patients morbidity and mortality rates in adult patients who were with subarachnoid haemorrhage could lead to yearly admitted to hospital for ruptured and unruptured savings of $11·4 million and $28·6 million, respectively intracranial aneurysms.48 Variables pertaining to hospital (Qureshi AI, unpublished). However, the cost savings admission were compared for three distinct time periods. and reduction in death and disability are obscured by the In-hospital mortality rates for patients with subarachnoid relatively small proportion of patients with subarachnoid haemorrhage demonstrated no significant change across haemorrhage who are considered for any aneurysm the different periods (27·6%, 24·6%, and 26·3% in treatment. We have reported that a third of patients 1986–90, 1991–95, and 1996–2001, respectively), but rates admitted to hospital in the USA with subarachnoid decreased across the three periods for patients with haemorrhage and half of those admitted with unruptured unruptured intracranial aneurysms (5·9%, 6·3%, and intracranial aneurysms underwent either surgical or 1·4%, respectively; p=0·07). endovascular treatment.48 Cross and colleagues49 reported A UK-based single-centre study51 investigated changes that 34% of 16 399 admissions for subarachnoid in clinical therapy and outcome of 1609 patients with haemorrhage in 18 US states from 1998 to 2000 resulted subarachnoid haemorrhage over 9 years (1990–98). in either surgical (29%) or endovascular (5%) treatment Overall, 54% of patients (ranging from 35% to 66%) were for intracranial aneurysms. However, the proportion of surgically treated, 8% had endovascular treatment patients eligible for such treatment is likely to be (0·6%–18%), and 38% (28%–46%) were managed without higher—for example, Fogelholm and colleagues50 surgical treatment for the aneurysm. The proportion of estimated that about 60% of patients with subarachnoid patients undergoing surgery decreased from 1994 Patients with ruptured intracranial aneurysms Patients with unruptured intracranial aneurysms Candidates for any treatment* Candidates for either treatment† Candidates for any treatment* Candidates for either treatment† Aneurysm obliteration Higher with surgical treatment (SCS)17,18 Higher with surgical treatment (RCT)32 Higher with surgical treatment ·· (SCS)17,18 Cerebral vasospasm Higher with endovascular treatment (SCS)19 ·· ·· ·· Discharge outcome Better with endovascular treatment (SCS)‡17 ·· Better with endovascular treatment Better with endovascular treatment (MOS)26,27 (SCS)14 Hospital charges No difference (SCS)20 No difference (SCS)36 Lower with endovascular treatment Lower with endovascular treatment (MOS)26,27 (SCS)14 2–6 month outcome ·· Better with endovascular treatment ·· ·· (RCT)32,33 1-year outcome ·· Better with endovascular treatment No difference (MOSI)11 ·· (RCT)32,33 Neuropsychiatric ·· No difference (RCT)30 No difference (MOSI)11 ·· outcomes Perioperative and long- ·· Lower with endovascular treatment (RCT)33 ·· ·· term risk of seizures Quality of life (1-year ·· ·· Better with endovascular treatment ·· outcomes) (MOS)39 Early rebleeding§ ·· No difference (RCT)33 ·· ·· Late rebleeding No difference (MOSI)29 No difference (RCT)33 ·· No difference (SCS)15 Second treatment Higher with endovascular treatment Higher with endovascular treatment (RCT)34 ·· ·· (MOSI)29 Late survival ·· Better with endovascular treatment (RCT)33 ·· ·· *Includes patients who were candidates for only surgical or only endovascular treatment. Endovascular treatment was preferentially used for patients with poor clinical and angiographic characteristics. †Patients for whom both endovascular and surgical treatments were acceptable options. ‡Not consistently demonstrated. §Rate of rebleeding was higher within 1 month after treatment in the endovascular-treated patients, but overall rate of rebleeding within 1 month was similar in the two groups because the rate of rebleeding was higher before the procedure in surgery-treated patients than in endovascular-treated patients. SCS=single-centre study. MOS=multicentre observational study. Double dots indicate that we found no relevant studies. MOSI=multicentre observational study with independent outcome ascertainment. RCT=randomised controlled trial. Table 2: Comparison of endovascular and surgical treatments 822 http://neurology.thelancet.com Vol 6 September 2007
  • 8. Review onwards, owing to improvements in endovascular treatment and higher rates of admission for patients with Search strategy and selection criteria poor-grade aneurysms. This change in admissions can We based the review on personal knowledge of the subject also explain an increase in mortality rate during the supplemented by data from multicentre randomised trials, period of review (from 18% to 32%). non-randomised controlled studies with independent The benefits of endovascular treatment are obscured in outcome ascertainment, and selected observational studies. patients with subarachnoid haemorrhage by preferential The information was identified with multiple searches of use of this treatment for patients with poor-grade Medline from January, 1985, to May, 2007, by cross- aneurysms, in whom outcome is predominantly referencing key words of “intracranial aneurysms”, determined by initial clinical condition. Similarly, “subarachnoid haemorrhage”, “embolization”, and endovascular treatment has increased the proportion of “detachable coils”. Only papers published in English were elderly patients who are treated for ruptured aneurysms; reviewed. We also reviewed abstracts from pertinent scientific in these patients, short-term and long-term survival is meetings, and information about technological developments partly influenced by comorbidities, which limits the was acquired through industrial resources available for clinical overall benefit of aneurysm treatment. Nevertheless, investigators. endovascular treatment has greatly improved the overall outcomes of patients with unruptured intracranial aneurysms. to 31% following publication of the ISAT results, whereas endovascular treatment of aneurysms increased from Implications of ISAT 35% to 68%. During the same period, there was a non- ISAT is to our knowledge the most comprehensive significant improvement in outcome at 6 months and a comparison of endovascular and surgical treatments. decrease in the mean total duration of hospital stay, However, results suggest that the patients treated in ISAT which was related to the shorter duration of hospital stay had more favourable baseline clinical and procedural associated with endovascular treatment than with characteristics than do patients with aneurysms treated surgery. Another study55 analysed the therapeutic outside this study. For example, a comparison of patients decision-making process and outcome in 100 consecutive admitted with subarachnoid haemorrhage to a nationally patients with subarachnoid haemorrhage treated since representative sample of hospitals in the USA48 showed the publication of ISAT. 47 patients underwent surgery, that the mean age of patients was lower in ISAT.32 In- 41 underwent endovascular treatment, and 12 received a hospital mortality was also lower (6% overall in ISAT32 vs combination of the two procedures. Good functional 26% for patients with subarachnoid haemorrhage in the outcome (mRS 0–2) after 6 months was achieved in 71% USA48). Similarly, the mortality in ISAT patients was of patients. This result suggests that, in routine clinical lower than that reported in the Japanese Standard Stroke practice, excellent functional results can be seen when Registry Study (22%).52 surgical and endovascular treatments are assigned on the Despite this difference, results from another study basis of data from ISAT. suggest that ISAT can be applied to the general population. Flett and colleagues53 reported on patients Conclusions who were admitted to one centre that participated in Endovascular treatment has been incorporated into the ISAT but who were not recruited into the trial (72% of all treatment of patients with subarachnoid haemorrhage admissions to the centre; most exclusions from ISAT who are poor candidates for surgical treatment. Since the were because one treatment was judged to be preferable emergence of endovascular treatments, reports such as to the other by the treating physicians, on the basis of ISAT have supported the idea that endovascular treatment morphology and location of the aneurysm or clinical is a valid alternative for many patients (table 2). However, characteristics of the patient). Nine of these patients were the definition of these patients is arbitrary, and the treated conservatively, 67 underwent surgical treatment, decision to use endovascular treatment for unruptured and 46 underwent endovascular treatment. At 12 months, intracranial aneurysms can depend on the views and 72% of the patients who received endovascular treatment expertise in local institutions. A better understanding of and 49% of those who received surgery had a good mRS the long-term risk of rupture, periprocedural results, and (0–2). This higher rate of favourable outcomes in patients complications associated with available procedures is who received endovascular treatment than in those who helping to clarify whether therapeutic intervention is received surgery provides evidence that the results of beneficial for unruptured intracranial aneurysms. Future ISAT can be applied generally. research priorities include a comparison of treatments for The proportion of patients undergoing endovascular unruptured intracranial aneurysms that can be treated by treatment has increased since the publication of ISAT. In either surgical or endovascular treatment, and a a report from a single neurosurgical unit in the UK,54 the comparison of treatments for ruptured intracranial proportion of patients with subarachnoid haemorrhage aneurysms in patient populations not included in ISAT, who underwent surgical treatment decreased from 51% with use of randomised clinical trials and prospective http://neurology.thelancet.com Vol 6 September 2007 823
  • 9. Review multicentre registries with independent outcome 19 Gruber A, Ungersbock K, Reinprecht A, et al. Evaluation of ascertainment. As physicians, we should use data to guide cerebral vasospasm after early surgical and endovascular treatment of ruptured intracranial aneurysms. Neurosurgery 1998; our decisions on a case-by-case basis, and we should 42: 258–67. remember that selection of appropriate patients for each 20 Bairstow P, Dodgson A, Linto J, Khangure M. Comparison of cost therapeutic method can improve the overall results. and outcome of endovascular and neurosurgical procedures in the treatment of ruptured intracranial aneurysms. Contributors Australas Radiol 2002; 46: 249–51. All authors contributed equally to the literature search, writing, and 21 Kato Y, Sano H, Dong PT, et al. The effect of clipping and coiling in revision of the manuscript. All authors have seen and approved the final acute severe subarachnoid hemorrhage after international version. subarachnoid aneurysmal trial (ISAT) results. Minim Invasive Neurosurg 2005; 48: 224–27. Conflicts of interest 22 Taha MM, Nakahara I, Higashi T, et al. Endovascular embolization We have no conflicts of interest. vs surgical clipping in treatment of cerebral aneurysms: morbidity References and mortality with short-term outcome. Surg Neurol 2006; 1 Qureshi AI. Endovascular treatment of cerebrovascular diseases 66: 277–84. and intracranial neoplasms. Lancet 2004; 363: 804–13. 23 Hoh BL, Topcuoglu MA, Singhal AB, et al. Effect of clipping, 2 Louw DF, Asfora WT, Sutherland GR. A brief history of aneurysm craniotomy, or intravascular coiling on cerebral vasospasm and clips. Neurosurg Focus 2001; 11: E4. patient outcome after aneurysmal subarachnoid hemorrhage. 3 Cohen-Gadol AA, Spencer DD. Harvey W. 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