Impact of Treatment Delay on Outcome in the International Subarachnoid Aneurysm Trial.

Background and Purpose- ISAT (International Subarachnoid Aneurysm Trial) demonstrated that 1 year after aneurysmal subarachnoid hemorrhage, coiling resulted in a significantly better clinical outcome than clipping. After 5 years, this difference did not reach statistical significance, but mortality was still higher in the clipping group. Here, we present additional analyses, reporting outcome after excluding pretreatment deaths. Methods- Outcome measures were death with or without dependency at 1 and 5 years after treatment, after exclusion of all pretreatment deaths. Treatment differences were assessed using relative risks (RRs). With sensitivity and exploratory analyses, the relation between treatment delay and outcome was analyzed. Results- After exclusion of pretreatment deaths, at 1-year follow-up coiling was favorable over clipping for death or dependency (RR, 0.77 [95% CI, 0.67-0.89]) but not for death alone (RR, 0.88 [95% CI, 0.66-1.19]). After 5 years, no significant differences were observed, neither for death or dependency (RR, 0.88 [95% CI, 0.77-1.02]) nor for death alone (RR, 0.82 [95% CI, 0.64-1.05]). Sensitivity analyses showed a similar picture. In good-grade patients, coiling remained favorable over clipping in the long-term. Time between randomization and treatment was significantly longer in the clipping arm (mean 1.7 versus 1.1 days; P<0.0001), during which 17 patients died because of rebleeding versus 6 pretreatment deaths in the endovascular arm (RR, 2.81 [95% CI, 1.11-7.11]). Conclusions- These additional analyses support the conclusion of ISAT that at 1-year follow-up after aneurysmal subarachnoid hemorrhage coiling has a better outcome than clipping. After 5 years, with pretreatment mortality excluded, the difference between coiling and clipping is not significant. The high number of pretreatment deaths in the clipping group highlights the importance of urgent aneurysm treatment to prevent early rebleeding.

Prediction of Outcome After Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- Early prediction of clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH) is still lacking accuracy. In this observational cohort study, we aimed to develop and validate an accurate bedside prediction model for clinical outcome after aSAH, to aid decision-making at an early stage. Methods- For the development of the prediction model, a prospectively kept single-center cohort of 1215 aSAH patients, admitted between 1998 and 2014, was used. For temporal validation, a prospective cohort of 224 consecutive aSAH patients from the same center, admitted between 2015 and 2017, was used. External validation was performed using the ISAT (International Subarachnoid Aneurysm Trial) database (2143 patients). Primary outcome measure was poor functional outcome 2 months after aSAH, defined as modified Rankin Scale score 4-6. The model was constructed using multivariate regression analyses. Performance of the model was examined in terms of discrimination and calibration. Results- The final model included 4 predictors independently associated with poor outcome after 2 months: age, World Federation of Neurosurgical Societies grade after resuscitation, aneurysm size, and Fisher grade. Temporal validation showed high discrimination (area under the receiver operating characteristic curve, 0.90; 95% CI, 0.85-0.94), external validation showed fair to good discrimination (area under the receiver operating characteristic curve, 0.73; 95% CI, 0.70-0.76). The model showed satisfactory calibration in both validation cohorts. The SAFIRE grading scale was derived from the final model: size of the aneurysm, age, Fisher grade, world federation of neurosurgical societies after resuscitation. Conclusions- The SAFIRE grading scale is an accurate, generalizable, and easily applicable model for early prediction of clinical outcome after aSAH.

Risk Analysis of Unruptured Intracranial Aneurysms: Prospective 10-Year Cohort Study.

BACKGROUND AND PURPOSE: The natural history of unruptured intracranial aneurysms remains unclear, and management strategy is not well defined. METHODS: From January 2003 to December 2012, we enrolled patients with aneurysm in our institution. In total, 2252 patients with 2897 aneurysms were eligible for analysis, and 1960 eligible aneurysms were conservatively managed. Precise 3-dimensional evaluation was conducted using computed tomography angiography, digital subtraction angiography, or magnetic resonance angiography. We then assessed the risk of aneurysm rupture, mortality, and morbidity associated with aneurysm characteristics, demographics, and known health/lifestyle risk factors. RESULTS: The mean follow-up duration was 7388 aneurysm-years. During observation, 56 aneurysms ruptured, resulting in an overall rupture rate per year of 0.76% (95% confidence interval, 0.58-0.98). The mean initial visit to rupture interval was 547 days. Aneurysm size, location, daughter sac, and history of subarachnoid hemorrhage were significant independent predictors for aneurysm rupture. Aneurysms that were ≥5 mm were associated with a significantly increased risk of rupture when compared with 2- to 4-mm aneurysms (unadjusted hazard ratio, 12.24; 95% confidence interval, 7.15-20.93). Of 56 patients who experienced hemorrhage, 29 (52 %) died or were rendered severely disabled. Of the patients who had large or giant aneurysms, none recovered without deficits, and the mortality rate after rupture was 69%. For aneurysms sized <5 mm, the mortality rate was 18%. CONCLUSIONS: Larger aneurysms are at greater risk for rupture and poor outcome. Ethnic factors may play a role in the risk of rupture.

The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT).

BACKGROUND: Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on the risks of recurrent subarachnoid haemorrhage and death or dependency for a minimum of 5 years and up to a maximum of 14 years after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling. At 1 year there was a 7% absolute and a 24% relative risk reduction of death and dependency in the coiling group compared with the clipping group, but the medium-term results showed the increased need for re-treatment of the target aneurysm in the patients given coiling. We report the long-term follow-up of patients in this UK cohort. METHODS: In ISAT, patients were randomly allocated to either neurosurgical clipping or endovascular coiling after a subarachnoid haemorrhage, assuming treatment equipoise, between Sept 12, 1994, and May 1, 2002. We followed up 1644 patients in 22 UK neurosurgical centres for death and clinical outcomes for 10·0-18·5 years. We assessed dependency as self-reported modified Rankin scale score obtained through yearly questionnaires. Data for recurrent aneurysms and rebleeding events were collected from questionnaires and from hospital and general practitioner records. The Office for National Statistics supplied data on deaths. This study is registered, number ISRCTN49866681. FINDINGS: At 10 years, 674 (83%) of 809 patients allocated endovascular coiling and 657 (79%) of 835 patients allocated neurosurgical clipping were alive (odds ratio [OR] 1·35, 95% CI 1·06-1·73). Of 1003 individuals who returned a questionnaire at 10 years, 435 (82%) patients treated with endovascular coiling and 370 (78%) patients treated with neurosurgical clipping were independent (modified Rankin scale score 0-2; OR 1·25; 95% CI 0·92-1·71). Patients in the endovascular treatment group were more likely to be alive and independent at 10 years than were patients in the neurosurgery group (OR 1·34, 95% CI 1·07-1·67). 33 patients had a recurrent subarachnoid haemorrhage more than 1 year after their initial haemorrhage (17 from the target aneurysm). INTERPRETATION: Although rates of increased dependency alone did not differ between groups, the probability of death or dependency was significantly greater in the neurosurgical group than in the endovascular group. Rebleeding was more likely after endovascular coiling than after neurosurgical clipping, but the risk was small and the probability of disability-free survival was significantly greater in the endovascular group than in the neurosurgical group at 10 years. FUNDING: UK Medical Research Council.

Aneurysm treatment <24 versus 24-72 h after subarachnoid hemorrhage.

INTRODUCTION: In patients with aneurysmal subarachnoid hemorrhage (aSAH), it is unclear whether aneurysm treatment <24 h after ictus results in better outcomes than treatment 24-72 h after aSAH. We studied whether aneurysm occlusion <24 h is associated with better outcomes than occlusion 24-72 h after aSAH. METHODS: We used two cohorts of patients with aSAH: (1) the UMC Utrecht cohort with patients admitted between 2008 and 2012 and (2) the International Subarachnoid Aneurysm Trial cohort. Aneurysm treatment was categorized into <24 h and 24-72 h after ictus. We calculated adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) using Poisson regression analyses for poor functional outcome (death or dependency) for both cohorts separately, and performed a pooled analysis based on individual patient data. We also performed a worst-case scenario analysis wherein all patients with rebleeding >3 h after admission were re-categorized into the group with aneurysm treatment 24-72 h after aSAH. RESULTS: We included 1,238 patients (UMC Utrecht cohort: n = 330; ISAT: n = 908). The aRR for poor outcome after treatment <24 h was in the UMC Utrecht cohort 1.84 (95% CI: 1.25-2.70), in ISAT 1.14 (95% CI 0.84-1.55), in the pooled analysis 1.37 (95% CI 1.11-1.68), and in the worst-case scenario pooled analysis 1.24 (95% CI 1.01-1.52). CONCLUSION: Our results suggest that aneurysm occlusion can be performed in day time within 72 h after ictus, instead of on an emergency basis. However, due to the retrospective, non-randomized design of our study, our results cannot be considered as definitive evidence.

Timing of aneurysm treatment after subarachnoid hemorrhage: relationship with delayed cerebral ischemia and poor outcome.

BACKGROUND AND PURPOSE: The ideal timing of coiling or clipping after aneurysmal subarachnoid hemorrhage is unknown. Within the International Subarachnoid Aneurysm Trial we assessed differences in incidence of delayed cerebral ischemia and clinical outcome between different timings of treatment. METHODS: The treated 2106 patients randomized to coiling or clipping were divided into 4 categories: treatment <2 days, on days 3 to 4, on days 5 to 10, and >10 days after the hemorrhage. ORs with 95% CI were calculated with logistic regression analysis for delayed cerebral ischemia, poor outcome at 2 months, and 1 year for the different timing categories, with treatment <2 days as reference. Analyses were performed for all patients, and for coiled and clipped patients separately, and were adjusted for baseline characteristics. RESULTS: Adjusted ORs of delayed cerebral ischemia for treatment on days 5 to 10 were 1.18 (95% CI, 0.91-1.53) for all patients, 1.68 (95% CI, 1.17-2.43) after coiling, and 0.79 (95% CI, 0.54-1.16) after clipping. ORs for poor outcome at 2 months were 1.16 (95% CI, 0.89-1.50) for treatment (clipping and coiling combined) at 3 to 4 days, 1.39 (95% CI, 1.08-1.80) for treatment at 5 to 10 days, and 1.84 (95% CI, 1.36-2.51) for treatment >10 days. ORs for coiled and clipped patients separately were in the same range. Results for outcome at 1 year were similar. CONCLUSIONS: Our results support the current practice for early aneurysm treatment in subarachnoid hemorrhage patients. The risk for poor outcome was highest when treatment was performed after day 10; postponing treatment in patients who are eligible for treatment between days 5 to 10 after subarachnoid hemorrhage is not recommended.

Cerecyte coil trial: angiographic outcomes of a prospective randomized trial comparing endovascular coiling of cerebral aneurysms with either cerecyte or bare platinum coils.

BACKGROUND AND PURPOSE: We report the primary outcome of the Cerecyte Coil Trial, a randomized trial to determine whether polymer-loaded Cerecyte coils compared with Micrus bare platinum coils improved the proportion of patients with angiographic occlusion of the aneurysm at 6 months when assessed by a core laboratory. The secondary objectives were to compare the clinical outcomes and retreatment rates in the 2 groups. METHODS: Five hundred patients between 18 and 70 years of age with a ruptured or unruptured target aneurysm were randomized to be treated with either Cerecyte or bare platinum coils in 23 centers worldwide. Two hundred forty-nine patients were assigned to Cerecyte coils and 251 to bare platinum coils. Analysis was by intention to treat. RESULTS: Four hundred ninety-four patients were eligible for analysis. Four hundred eighty-one patients underwent coil treatment of their aneurysm, 227 patients with recently ruptured aneurysms and 254 with unruptured aneurysms. Four hundred thirty-three follow-up angiograms were assessed by the core laboratory; 127 of 215 (59%) and 118 of 218 (54%) in the Cerecyte and bare platinum groups, respectively, fulfilled the trial prespecified definition of success, namely that the treated aneurysm showed complete angiographic occlusion, had stable neck remnant, or improved in angiographic appearance compared with the end-of-treatment angiogram (P=0.17). Late retreatment was performed in 25 of 452 (5.5%) patients, 17 (7.7%) Cerecyte versus 8 (3.5%) bare platinum (P=0.064; range, 4-34 months). The clinical outcomes did not differ between the groups. CONCLUSIONS: There was no significant difference at 6 months in the angiographic outcomes between Cerecyte coils and bare platinum coils when assessed by the core laboratory. Clinical Trial Registration Information- URL: www.controlled-trials.com. Unique Identifier: ISRCTN82461286.

Survival, Dependency, and Health-Related Quality of Life in Patients With Ruptured Intracranial Aneurysm: 10-Year Follow-up of the United Kingdom Cohort of the International Subarachnoid Aneurysm Trial.

BACKGROUND: Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on clinical outcomes after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling. OBJECTIVE: To evaluate the long-term quality-adjusted life years (QALYs) gained of endovascular coiling compare to neurosurgical clipping in the UK cohort of ISAT. METHODS: Between September 12, 1994 and May 1, 2002, patients with ruptured intracranial aneurysms who were assumed treatment equipoise were randomly allocated to either neurosurgical clipping or endovascular coiling. We followed-up 1644 patients in 22 UK neurosurgical centers for a minimum of 10 yr. Health-related quality of life (HRQoL) was collected through yearly questionnaires, measured by utilities calculated from the EQ-5D-3L. We compared HRQoL between the 2 treatment groups over a period of 10 yr. In all, 1-yr, 5-yr, and 10-yr QALYs were estimated by combining utility and survival information. RESULTS: Higher average utility values were found in the endovascular group throughout the follow-up period, with mean differences between groups statistically significant in most years. The 10-yr QALYs were estimated to be 6.68 (95% CI: 6.45-6.90) in the coiling group and 6.32 (95% CI: 6.10-6.55) in the clipping group, respectively, a significant mean difference of 0.36 (95% CI: 0.04-0.66). A third of this mean QALYs gain was estimated to derive solely from HRQoL differences. CONCLUSION: HRQoL after treatment of a ruptured intracranial aneurysm was better after endovascular coiling compared to neurosurgical clipping, which contributed significantly to the QALYs gained over a 10-yr period.

Improved cognitive outcomes with endovascular coiling of ruptured intracranial aneurysms: neuropsychological outcomes from the International Subarachnoid Aneurysm Trial (ISAT).

BACKGROUND AND PURPOSE: The International Subarachnoid Aneurysm Trial (ISAT) reported lower rates of death and disability with endovascular versus neurosurgical treatment of ruptured intracranial aneurysms. However, assessment of functional outcome was limited to the modified Rankin Scale, which is known to be insensitive to cognitive function. A neuropsychological substudy (N-ISAT) was therefore done in all recruits from 8 ISAT centers in the United Kingdom. METHODS: Detailed neuropsychological assessment was performed at a 12-month follow-up visit. Impairment was defined as performance below the 5th percentile of the study population on at least 2 tests in >or=2 major cognitive domains. Analysis was restricted to patients who were not known to be otherwise disabled according to the modified Rankin Scale (ie, modified Rankin Scale 0 to 2). RESULTS: Of 836 patients randomized in ISAT in the 8 UK centers (411 allocated endovascular treatment versus 425 neurosurgery), 224 were dead or disabled before 12-month follow-up (78 allocated endovascular treatment versus 135 neurosurgery). Of the remaining 612 patients eligible for neuropsychological assessment, 137 (65 allocated endovascular treatment versus 72 neurosurgery) did not attend. Of the 474 nondisabled patients who were assessed, 152 (32.1%) had cognitive impairment. Patients with cognitive impairment had reduced self-reported health-related quality of life (P<0.001) in both treatment groups, but cognitive impairment was less common in those allocated endovascular treatment (70 of 262 versus 82 of 212 allocated neurosurgery, OR=0.58, 95% CI 0.38 to 0.87, P=0.0055). The incidence of epilepsy was also lower in the N-ISAT endovascular group (7 versus 18, OR=0.30, 0.11 to 0.77, P=0.005) but was independent of the effect on cognitive function. CONCLUSIONS: Cognitive impairment occurred in approximately one third of patients who were not otherwise disabled according to the modified Rankin Scale in N-ISAT and was more frequent in the neurosurgery group. These results have implications for management of ruptured intracranial aneurysms and more generally for interpretation of the outcomes of clinical trials that use the modified Rankin Scale.

Prediction of two month modified Rankin Scale with an ordinal prediction model in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with a frequently disabling outcome. Our aim was to develop a prognostic model to predict an ordinal clinical outcome at two months in patients with aSAH. METHODS: We studied patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomized multicentre trial to compare coiling and clipping in aSAH patients.Several models were explored to estimate a patient's outcome according to the modified Rankin Scale (mRS) at two months after aSAH. Our final model was validated internally with bootstrapping techniques. RESULTS: The study population comprised of 2,128 patients of whom 159 patients died within 2 months (8%). Multivariable proportional odds analysis identified World Federation of Neurosurgical Societies (WFNS) grade as the most important predictor, followed by age, sex, lumen size of the aneurysm, Fisher grade, vasospasm on angiography, and treatment modality. The model discriminated moderately between those with poor and good mRS scores (c statistic = 0.65), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.64). CONCLUSION: We presented a calibrated and internally validated ordinal prognostic model to predict two month mRS in aSAH patients who survived the early stage up till a treatment decision. Although generalizability of the model is limited due to the selected population in which it was developed, this model could eventually be used to support clinical decision making after external validation. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, Number ISRCTN49866681.

Effect of antiplatelet therapy for endovascular coiling in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Antiplatelets are frequently used during or after endovascular coiling of aneurysm in patients with subarachnoid hemorrhage (SAH). This strategy is based on uncontrolled case series including also patients with unruptured aneurysms or other lesions. We collected data on effectiveness of antiplatelets in patients with SAH. METHODS: All 43 participating centers in the International Subarachnoid Aneurysm Trial (ISAT) were sent a questionnaire whether they never, sometimes, or always prescribed antiplatelets during or after coiling. Based on individual patient data, the relative risks (RRs) of coiling versus clipping were calculated separately for patients treated in hospitals with standard prescription during or after coiling versus patients treated in hospitals with no standard prescription of antiplatelets. We calculated ratios of RRs for standard versus not standard prescription of antiplatelets during coiling and for standard versus not standard prescription after coiling. RESULTS: Nineteen centers responded, representing 1422 (66%) of the 2143 ISAT patients. Antiplatelets were standard prescribed during coiling in 2 responding centers (8% of coiled patients) and after coiling in 6 centers (24%). For poor outcome at 2 months of coiling versus clipping the RR was 0.82 (95% CI: 0.45 to 1.49) in hospitals with a policy of antiplatelet prescription during coiling versus 0.66 (95% CI: 0.55 to 0.78) in those without such policy (ratio of RR's 1.24, P=0.56). The ratio of RRs for 1-year outcome was 1.01 (P=0.89) for antiplatelet use during coiling and 1.00 (P=0.77) for use after coiling. CONCLUSIONS: The results of this study do not support the assumption that antiplatelets during or after endovascular coiling improve outcome in patients with SAH.

Substantial observer variability in the differentiation between primary intracerebral hemorrhage and hemorrhagic transformation of infarction on CT brain imaging.

BACKGROUND AND PURPOSE: CT remains the most commonly used imaging technique in acute stroke but is often delayed after minor stroke. Interobserver reliability in distinguishing hemorrhagic transformation of infarction from intracerebral hemorrhage may depend on delays to CT but has not been reported previously despite the clinical importance of this distinction. METHODS: Initial CT scans with intraparenchymal hematoma from the first 1000 patients with stroke in the Oxford Vascular Study were independently categorized as intracerebral hemorrhage or hemorrhagic transformation of infarction by 5 neuroradiologists, both blinded and unblinded to clinical history. Thirty scans were reviewed twice. Agreement was quantified by the kappa statistic. RESULTS: Seventy-eight scans showed intraparenchymal hematoma. Blinded pairwise interrater agreements for a diagnosis of intracerebral hemorrhage ranged from kappa=0.15 to 0.48 with poor overall agreement (kappa=0.35; 95% CI, 0.15 to 0.54) even after unblinding (kappa=0.41; 0.21 to 0.60). Blinded intrarater agreements ranged from kappa=0.21 to 0.92. Lack of consensus after unblinding was greatest in patients scanned >or=24 hours after stroke onset (67% versus 25%, P=0.001) and in minor stroke (National Institutes of Health Stroke Scale or=24 hours after minor stroke and in 48% of all 30-day stroke survivors in whom reliable diagnosis would be expected to influence long-term management. CONCLUSIONS: Reliability of diagnosis of intraparenchymal hematoma on CT brain scan in minor stroke is poor, particularly if scanning is delayed. Immediate brain imaging is justified in patients with minor stroke.

Variation in outcome after subarachnoid hemorrhage: a study of neurosurgical units in UK and Ireland.

BACKGROUNDS AND PURPOSE: The purpose of the study was to describe the characteristics, management, and outcomes of patients with confirmed aneurysmal subarachnoid hemorrhage and to compare outcomes across neurosurgical units (NSUs) in the UK and Ireland. METHODS: A cohort of patients admitted to NSUs with subarachnoid hemorrhage between September 14, 2001 and September 13, 2002 was studied longitudinally. Information was collected to characterize clinical condition on admission and treatment. Death or severe disability, defined by the Glasgow Outcome Score-Extended, was ascertained at 6 months. RESULTS: Data for 2397 patients with a confirmed aneurysm and no coexisting neurological pathology were collected by all 34 NSUs in the UK and Ireland. Aneurysm repair was attempted in 2198 (91.7%) patients (surgical clipping, 57.7%; endovascular coiling, 41.2%; other repair, 1.0%). Most patients (65.0%) were admitted to the NSU on the same day or the day after their hemorrhage; 32.0% of treated patients had the aneurysm repaired on the day of admission to the NSU (day 0), day 1 or day 2 and a further 39.3% by day 7. Glasgow Outcome Score-Extended at 6 months was obtained for 90.6% of patients (2172), of whom 38.5% had an unfavorable outcome. The median risk of an unfavorable outcome for all patients was 31% (5(th) and 95(th) percentiles, 12% and 83%), depending on prerepair prognostic factors. After adjustment for case-mix, the percentage of patients with an unfavorable outcome in each NSU did not differ significantly from the overall mean. CONCLUSIONS: In this study that collected representative data from the UK and Ireland, there was no evidence that the performance of any NSU differed from the average.

Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-up.

BACKGROUND: Our aim was to assess the long-term risks of death, disability, and rebleeding in patients randomly assigned to clipping or endovascular coiling after rupture of an intracranial aneurysm in the follow-up of the International Subarachnoid Aneurysm Trial (ISAT). METHODS: 2143 patients with ruptured intracranial aneurysms were enrolled between 1994 and 2002 at 43 neurosurgical centres and randomly assigned to clipping or coiling. Clinical outcomes at 1 year have been previously reported. All UK and some non-UK centres continued long-term follow-up of 2004 patients enrolled in the original cohort. Annual follow-up has been done for a minimum of 6 years and a maximum of 14 years (mean follow-up 9 years). All deaths and rebleeding events were recorded. Analysis of rebleeding was by allocation and by treatment received. ISAT is registered, number ISRCTN49866681. FINDINGS: 24 rebleeds had occurred more than 1 year after treatment. Of these, 13 were from the treated aneurysm (ten in the coiling group and three in the clipping group; log rank p=0.06 by intention-to-treat analysis). There were 8447 person-years of follow-up in the coiling group and 8177 person-years of follow-up in the clipping group. Four rebleeds occurred from a pre-existing aneurysm and six from new aneurysms. At 5 years, 11% (112 of 1046) of the patients in the endovascular group and 14% (144 of 1041) of the patients in the neurosurgical group had died (log-rank p=0.03). The risk of death at 5 years was significantly lower in the coiling group than in the clipping group (relative risk 0.77, 95% CI 0.61-0.98; p=0.03), but the proportion of survivors at 5 years who were independent did not differ between the two groups: endovascular 83% (626 of 755) and neurosurgical 82% (584 of 713). The standardised mortality rate, conditional on survival at 1 year, was increased for patients treated for ruptured aneurysms compared with the general population (1.57, 95% CI 1.32-1.82; p<0.0001). INTERPRETATION: There was an increased risk of recurrent bleeding from a coiled aneurysm compared with a clipped aneurysm, but the risks were small. The risk of death at 5 years was significantly lower in the coiled group than it was in the clipped group. The standardised mortality rate for patients treated for ruptured aneurysms was increased compared with the general population. FUNDING: UK Medical Research Council.

International subarachnoid aneurysm trial of neurosurgical clipping versus endovascular coiling: subgroup analysis of 278 elderly patients.

BACKGROUND AND PURPOSE: It is often thought that elderly patients in particular would benefit from endovascular aneurysm treatment. The aim of this analysis was therefore to compare the efficacy and safety of endovascular coiling (EVT) with neurosurgical clipping (NST) in the subgroup of elderly SAH patients in the International Subarachnoid Aneurysm Trial (ISAT). METHODS: In the ISAT cohort 278 SAH patients, 65 years or older, were enrolled. The patients were randomly allocated EVT (n=138) or NST (n=140). The primary outcome was the proportion of patients with a modified Rankin scale score of 0 to 2 (independent survival) at 1 year after the SAH. The rates of procedural complications and adverse events were also recorded. RESULTS: 83 of 138 (60.1%) patients allocated EVT were independent compared to 78 of 140 (56.1%) allocated NST (N.S.). 36 of 50 (72.0%) patients with internal carotid and posterior communicating artery aneurysms allocated EVT were independent compared to 26 of 50 (52.0%) allocated NST (P<0.05). 10 of 22 (45.5%) patients with middle cerebral artery aneurysms allocated EVT were independent compared to 13 of 15 (86.7%) allocated NST (P<0.05). The epilepsy frequency was 0.7% in the EVT group compared to 12.9% in the NST group (P<0.001). CONCLUSIONS: In good grade elderly SAH patients with small anterior circulation aneurysms, EVT should probably be the favored treatment for ruptured internal carotid and posterior communicating artery aneurysms, whereas elderly patients with ruptured middle cerebral artery aneurysms appear to benefit from NST. EVT resulted in a lower epilepsy frequency than NST.

Treatment pathways, resource use, and costs of endovascular coiling versus surgical clipping after aSAH.

BACKGROUND AND PURPOSE: The International Subarachnoid Aneurysm Trial (ISAT) reported that endovascular coiling yields better clinical outcomes than surgical clipping at 1 year. The high cost of the consumables associated with the endovascular coiling procedure (particularly the coils) led health care purchasers to conclude that coiling was a more costly procedure overall. To examine this assumption and provide evidence for future policy, accurate and comprehensive data are required on the overall resource usage and cost of each strategy. METHODS: We provide detailed results of patient treatment pathways, resource utilization, and costs up to 24 months postrandomization for endovascular and neurosurgical treatment of aSAH. We report data on costs related to initial and subsequent procedures (ward days, ITU, equipment, staff, consumables, etc), adverse events, complications, and follow up. The data are based on a subsample of all patients randomized in ISAT, containing all patients across 22 UK centers (n=1644). RESULTS: There was a nonsignificant difference - pound 1740 (- pound 3582 to pound 32) in the total 12-month cost of treatment in favor of endovascular treatment. Endovascular patients had higher costs than neurosurgical patients for the initial procedure, for the number and length of stay of subsequent procedures, and for follow-up angiograms. These were more than offset by lower costs related to length of stay for the initial procedure. In the following 12- to 24-month period, costs for subsequent procedures, angiograms, complications, and adverse events were greater for the endovascular patients, reducing the difference in total per patient cost to - pound 1228 (- pound 3199 to pound 786) over the first 24 months of follow-up. CONCLUSIONS: No significant difference in costs between the endovascular and neurosurgery groups existed at 12- or 24-month follow up.

Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the International Subarachnoid Aneurysm Trial (ISAT).

BACKGROUND AND PURPOSE: Because the long-term security of endovascular treatments remains uncertain, a follow-up study of the patients treated in the International Subarachnoid Aneurysm Trial was performed to compare the frequency, timing, and consequences of aneurysm recurrence. METHODS: Patient data were reclassified by actual treatment performed. Aneurysm and patient characteristics, including occlusion grades, time and type of retreatment, and clinical outcomes, were compared. The relationship between these variables and late retreatment as a surrogate for recurrence was analyzed by means of the Cox proportional hazards model. RESULTS: Retreatment was performed in 191 of 1096 (17.4%) patients after primary endovascular coiling (EVT) and in 39 of 1012 patients (3.8%) after neurosurgical clipping. After EVT, 97 (8.8%) patients were retreated early and 94 (9.0%) late, 7 (0.6%) after rebleeding and 87 (8.3%) without. The mean time to late retreatment was 20.7 months. After neurosurgical clipping, 30 (2.9%) patients were retreated early and 9 (0.85%) late, 3 (0.3%) after rebleeding and 6 (0.6%) without. The mean time to late retreatment was 5.7 months. The hazard ratio (HR) for retreatment after EVT was 6.9 (95% CI=3.4 to 14.1) after adjustment for age (P=0.001, HR=0.97, 95% CI=0.95 to 0.98), lumen size (P=0.006, HR=1.1, 95% CI=1.03 to 1.18), and incomplete occlusion (P<0.001, HR=7.6, 95% CI=3.3 to 17.5). CONCLUSIONS: Late retreatment was 6.9 times more likely after EVT. Younger age, larger lumen size, and incomplete occlusion were risk factors for late retreatment after EVT. After neurosurgical clipping, retreatments were earlier; whereas EVT retreatments continued to be performed throughout the follow-up period. Short-term follow-up imaging is therefore insufficient to detect recurrences after EVT.

Embolization of spinal intramedullary arteriovenous malformations using the liquid embolic agent, Onyx: a single-center experience in a series of 17 patients.

OBJECT: The aim of this study was to analyze the endovascular treatment results of using the Onyx liquid embolic system for spinal intramedullary arteriovenous malformations (AVMs). METHODS: The clinical and radiological records of 17 patients with symptomatic spinal intramedullary AVMs treated exclusively by embolization with Onyx between 1999 and 2003 were retrospectively reviewed. There were 12 females and five males in the patient series (mean age 29 years). Four of these AVMs were located in the cervical spine, eight in the thoracic spine, and five in the lumbar spine. The clinical presentation of these AVMs included upper motor neuron signs and symptoms, and hemorrhage was the initial presentation in 12 patients. Neurological and functional evaluation was performed before and after treatment with Onyx in all patients. RESULTS: Thirteen patients underwent a single endovascular treatment and four patients underwent two endovascular treatments (average 1.23 sessions per patient). Intraprocedural complications occurred on two occasions without neurological consequences. The mean follow-up duration was 24.3 months. Angiographic outcomes included total AVM obliteration in six patients (37.5%), subtotal obliteration in five patients (31.25%), and partial obliteration in five patients (31.25%). Improvement in neurological and/or functional status was noted in 14 patients, resulting in an 82% rate of overall good clinical outcome. CONCLUSIONS: Embolization using the Onyx system is a promising treatment method for spinal vascular malformations, even for challenging intramedullary AVMs. Larger studies with longer follow-up durations will further enhance our knowledge on the safety and efficacy of this relatively new liquid embolic agent.