International Subarachnoid Aneurysm Trial Research Articles

To clip or to coil? That is no longer the question

The relative merits of clipping and endovascular coiling to treat ruptured intracranial aneurysms are the subject of an ongoing debate. The latest results from the International Subarachnoid Aneurysm Trial offer reassurance regarding the long-term outcomes of coiling and provide support for an individualized approach.

003 Quality of life in good outcome patients who underwent endovascular coiling for aneurysmal subarachnoid hemorrhage

Purpose: The International Subarachnoid Aneurysm Trial (ISAT) compared endovascular coiling and surgical clipping in randomized patients with intracranial aneurysm rupture. At the 12 month and 7 year follow-up evaluations, death...

025 Psychological impact of screening for aneurysm recurrence in good outcome patients who underwent endovascular coiling after subarachnoid hemorrhage

Purpose: Subjects allocated to endovascular coiling in the International Subarachnoid Aneurysm Trial (ISAT) had better outcomes at 12 months and during follow-up extended to 7 years. Still, concern about the...

Ruptured carotid artery aneurysms of the ophthalmic (C6) segment: clinical and angiographic long term follow-up of a multidisciplinary management strategy

Background:The management of ruptured C6 aneurysms remains controversial. Detailed long-term outcome data are still lacking. Thus the present study provided a detailed long term follow-up for a multidisciplinary approach combining...

To clip or to coil? Choosing the best treatment for cerebral aneurysms

Treatment of cerebral aneurysm has undergone many changes over the past 15 years. With the introduction of coiling under radiological guidance, surgical clipping is no longer the only available treatment. Many factors need to be considered when planning treatment including the patient's general health and the size and location of the aneurysm. The International Subarachnoid Aneurysm Trial (ISAT) (Molyneux et al, 2005) found that coiling is more likely to result in independent survival than clipping (P=0.0001). Further investigation and technological developments in both surgery and radiology have indicated that a multidisciplinary approach is required to achieve the best outcomes, and the most appropriate intervention for the individual patient is best decided on a case-by-case basis. Further research is needed to determine in which circumstances one treatment is superior to the other.

Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

To the Editor: We read a recent article published in Stroke which dealt with postoperative cerebral infarction after surgery of intracranial aneurysms.1 The article contained shortcomings on which we are obligated to comment. Contrary to the authors’ statement, there are several published articles on post-subarachnoid hemorrhage cerebral infarction mostly caused by either delayed cerebral ischemia or by aneurysm occlusion (with open surgery or endovascular occlusion).2–5 See also discussion sections of these articles for additional publications on this issue. We have done serial CT and MRI …

Cost-effectiveness analysis of endovascular versus neurosurgical treatment for ruptured intracranial aneurysms in the United States

The results of the International Subarachnoid Aneurysm Trial (ISAT) demonstrated lower rates of death and disability with endovascular treatment (coiling) than with open surgery (clipping) to secure the ruptured intracranial aneurysm. However, cost-effectiveness may not be favorable because of the greater need for follow-up cerebral angiograms and additional follow-up treatment with endovascular methods. In this study, the authors' goal was to compare the cost-effectiveness of endovascular and neurosurgical treatments in patients with ruptured intracranial aneurysms who were eligible to undergo either type of treatment. Clinical data (age, sex, frequency of retreatment, and rebleeding) and quality of life values were obtained from the ISAT. Total cost included those associated with disability, hospitalization, retreatment, and rebleeding. Cost estimates were derived from the Premier Perspective Comparative Database, data from long-term care in stroke patients, and relevant literature. Incremental cost-effectiveness ratios (ICERs) were estimated during a 1-year period. Parametric bootstrapping was used to determine the uncertainty of the estimates. The median estimated costs of endovascular and neurosurgical treatments (in US dollars) were $45,493 (95th percentile range $44,693-$46,365) and $41,769 (95th percentile range $41,094-$42,518), respectively. The overall quality-adjusted life years (QALY) in the endovascular group was 0.69, and for the neurosurgical group it was 0.64. The cost per QALY in the endovascular group was $65,424 (95th percentile range $64,178-$66,772), and in the neurosurgical group it was $64,824 (95th percentile range $63,679-$66,086). The median estimated ICER at 1 year for endovascular treatment versus neurosurgical treatment was $72,872 (95th percentile range $50,344-$98,335) per QALY gained. Given that most postprocedure angiograms and additional treatments occurred in the 1st year and the 1-year disability status is unlikely to change in the future, ICER for endovascular treatment will progressively decrease over time. Using outcome and economic data obtained in the US at 1 year after the procedure, endovascular treatment is more costly but is associated with better outcomes than the neurosurgical alternative among patients with ruptured intracranial aneurysms who are eligible to undergo either procedure. With accrual of additional years with a better outcome status, the ICER for endovascular coiling would be expected to progressively decrease and eventually reverse.

Effect of Antiplatelet Therapy for Endovascular Coiling in Aneurysmal Subarachnoid Hemorrhage

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. 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. 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. The results of this study do not support the assumption that antiplatelets during or after endovascular coiling improve outcome in patients with SAH.

Advances in Critical Care and Emergency Medicine

In 2008, there were clinical trial advances in 3 areas that will impact on the way stroke care is practiced in the emergency department and intensive care unit (ICU). These include (1) the positive results of the European Cooperative Acute Stroke Study (ECASS) III trial, extending the time window for intravenous thrombolytic therapy for acute ischemic stroke; (2) the negative results of 2 trials investigating the use of intensive insulin therapy in the ICU; and (3) new data from the Phase 2 Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT), investigating the role of intensive blood pressure (BP) control after intracerebral hemorrhage (ICH). Intravenous thrombolysis with alteplase is still the only approved treatment for acute ischemic stroke. However, the time window for applying this therapy, which significantly reduces morbidity but not mortality, up to now has been restricted to 3 hours after symptom onset.1 Various stroke trials trying to expand this strict time window, selecting patients based on CT or MRI perfusion, and using thrombolytic agents other than recombinant tissue plasminogen activator (rtPA), have up until now failed to prove efficacy regarding clinical end points.2–5 After a couple of years without any positive stroke trials, ECASS III adds on to the encouraging results of the pooled analyses of the ECASS and National Institute of Neurological Diseases and Stroke trials,6 now expanding the time window for CT-based treatment of acute ischemic stroke up to 4.5 hours.7 The ECASS III trial randomly assigned 821 patients either to receive 0.9 mg rtPA per kilogram body weight or placebo. After ruling out intracranial hemorrhage using CT, thrombolysis was administered between 3 and 4.5 hours (median, 4 hours). The dichotomized primary end point of recovery with no disability after 90 days (modified …

Vertebrobasilar Aneurysms: Need for Surgical Treatment?

The results of the International Subarachnoid Aneurysm Trial (ISAT) have shown that endovascular intervention with detachable platinum coils is superior to neurosurgical intervention with an absolute risk reduction of 8.7%. The results have led to practical consequences: Endovascular treatment has become the first option for management of cerebral aneurysm. Due to development in the technology of microcatheters, protecting balloons and stents, occlusion devices, and embolic materials, as well as the increase in knowledge and practical endovascular manual skills of the neuroradiologists, many aneurysms primarily assumed noncoilable can be coiled today. Also, the use of biologically active coils, liquid embolic agents such as ONYX, and bioactive coils coated with expansile hydrogel polymers has broadened the spectrum of treatable aneurysms. Because ∼90% of all aneurysms are endovascularly treatable, the predominant and, in some centers, nearly exclusive treatment of aneurysms by endovascular means is thus justified. Partial recanalization of aneurysms after coiling remains a basic problem, ranging between 0 and 35% depending on anatomy and the technique applied; however, the occurrence of this problem is decreasing because of the combined treatment modalities mentioned previously.

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

SummaryBackgroundOur 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).Methods2143 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.Findings24 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).InterpretationThere 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.FundingUK Medical Research Council.

The costs and prognostic characteristics of ischaemic neurological deficit due to subarachnoid haemorrhage in the United Kingdom

Delayed ischaemic neurological deficit (DID) following subarachnoid haemorrhage from aneurysm rupture (aSAH) is a serious complication and a major cause of mortality and morbidity. No empirical estimates of resource use and costs of patients with delayed ischaemic deficit compared to those without have been reported to date. A detailed cost analysis of the UK National Health Service health care costs of DID was performed using resource use data from the International Subarachnoid Aneurysm Trial (ISAT) over the 24 months following haemorrhage. Resource use categories included direct health care and employment-related costs. A prognostic model of baseline predictors of DID and overall total health care costs was also constructed. Mean (standard deviation) total health care costs at 24 months follow-up were estimated to be pound sterling 28175 (pound sterling 26773) in the DID group and pound sterling 18805 (pound sterling 17287) in the no DID group, a significant difference (95 % confidence interval) of pound sterling 9370 (pound sterling 6880 to pound sterling 12516). This cost difference was driven by statistically significant differences on imaging and investigations, longer length of stay and higher cost of complications and adverse events experienced by patients with DID. Patients with DID also spent on average 62 days less in paid employment than patients without this complication. The prognostic model found CT Fisher grading, WFNS grade, aneurysm location and time from aSAH to intervention statistically significant baseline predictors of delayed ischaemic deficit. Patients who developed DID incurred substantially higher costs and a significantly slower resumption of employment than patients without at 24 months follow-up after aSAH.

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) is a common and frequently devastating condition, accounting for ≈5% of all strokes and affecting as many as 30 000 Americans each year.1,2 The American Heart Association (AHA) previously published “Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage.”3 Since then, considerable advances have been made in endovascular techniques, diagnostic methods, and surgical and perioperative management paradigms. Nevertheless, outcome for patients with SAH remains poor, with population-based mortality rates as high as 45% and significant morbidity among survivors.4–9 Several multicenter, prospective, randomized trials and prospective cohort analyses have influenced treatment protocols for SAH. However, rapid evolution of newer treatment modalities, as well as other practical and ethical considerations, has meant that rigorous clinical scientific assessment of the treatment protocols has not been feasible in several important areas. To address these issues, the Stroke Council of the AHA formed a writing group to reevaluate the recommendations for management of aneurysmal SAH. A consensus committee reviewed existing data in this field and prepared the recommendations in 1994.3 In an effort to update those recommendations, a systematic literature review was conducted based on a search of MEDLINE to identify all relevant randomized clinical trials published between June 30, 1994, and November 1, 2006 (search terms: subarachnoid hemorrhage , cerebral aneurysm , trial ; Table 1). Each identified article was reviewed by at least 2 members of the writing group. Selected articles had to meet one of the following criteria to be included: randomized trial or nonrandomized concurrent cohort study. Case series and nonrandomized historical cohort studies were reviewed if no studies with a higher level of evidence were available for a particular topic covered in the initial guidelines. These were chosen on the basis of sample size and the relevance of the particular studies to subjects that …

Endovascular cerebral aneurysm treatment: Long-term outcomes

The International Subarachnoid Aneurysm Trial confirmed endovascular treatment as the treatment of choice for intracranial 'berry' aneurysms. The durability of coiling and the relevance of stable neck remnants needed to be addressed next. We retrospectively assessed the follow-up angiograms of patients who presented with subarachnoid haemorrhages or third-nerve palsies and had berry aneurysms treated endovascularly between 2002 and 2003. Patients were phoned to assess their wellbeing and to see whether they were back at work or not. Angiograms were assessed to ascertain the percentage of the aneurysm coiled at the initial procedure, and then stability was assessed by percentage change in the residual aneuysm neck on later angiograms. Over a 1-year period 75 patients were treated endovascularly; 100% occlusion was achieved in 52% at the initial procedure, and although only 40 and 34 respectively attended for 3-month and 1-year follow-up angiograms there was a trend toward progressive thrombosis in 65% and 82% respectively. In only 1 of the neck remnants was growth noted at the 3-month angiogram. One patient bled after missing his 3-month follow-up angiogram. Although only 40% of the patients were contactable at 4 years there were no rebleeds among them. Coiling is durable, as shown by our results over a 4-year period, and while neck remnants that look unchanged are generally stable any growth should be viewed as grounds for concern and treated either endovascularly or surgically if required. The 5-year angiogram may be unnecessary, which is of importance in our setting where socio-economic factors influence patient follow-up.

Vascular neurosurgery since the International Subarachnoid Aneurysm Trial

Vascular neurosurgery since the International Subarachnoid Aneurysm Trial

Vascular neurosurgery following the International Subarachnoid Aneurysm Trial: modern practice reflected by subspecialization

In this paper the authors' goal was to report on and examine (in the context of a large hospital with good endovascular intervention provisions) the activities of a neurosurgeon with a dedicated vascular interest in the era after the International Subarachnoid Aneurysm Trial in the United Kingdom. They also aimed to establish therapeutic trends and outcomes. The authors reviewed the multidisciplinary team activity of 1 neurosurgeon and 2 interventional radiologists during a period of 22 months (2005-2007). They reviewed 281 aneurysm interventions; the majority was used to treat subarachnoid hemorrhage. Data analysis showed a strong preference for endovascular treatment for acute rupture (86.6 vs 13.4%), with a progressively greater role for open microsurgery in the more elective context (57% endovascular vs 43% surgical). They also reviewed 66 interventions for arteriovenous malformations, of which only 6 were surgical. These data are compared against a sample year from 2001 to 2002 (pre-International Subarachnoid Aneurysm Trial), showing comparable rates of surgically treated aneurysms versus endovascularly treated aneurysms, but an increase overall in the number of patients requiring open surgery. The authors found that excellent outcomes for microsurgical clipping compared with endovascular therapy can be achieved within the current climate. These and previously published data strongly support a continuing role for vascular neurosurgery as a subspecialist interest in combination with a dedicated endovascular service and a multidisciplinary team. Despite a trend to prefer coiling for ruptured aneurysms, the authors have shown that there is still a vital role for open surgery in the management of the ruptured and unruptured aneurysm. They consider the remaining role for surgery for arteriovenous malformations within the modern era of endovascular therapy.

Materials and techniques for coiling of cerebral aneurysms: how much scientific evidence do we have?

Since coils were approved for aneurysm treatment, materials and techniques developed rapidly. It still remains an open question whether one material or method is superior. This article reviews the literature on various coil types and treatment approaches assessing the scientific evidence of its use. Studies on aneurysm treatment with Guglielmi detachable platinum coils, bioactive coils, hydrogel coated coils, and complex designs as well as balloon- and stent-assisted techniques were retrieved by a PubMed database search from 1990 until May 2008. Data were analyzed in terms of aneurysm occlusion, permanent morbidity and mortality, recanalization, and retreatment. We also assessed the level of evidence of the published studies. Only the International Subarachnoid Aneurysm Trial provides level I evidence proving the superiority of endovascular over surgical therapy in ruptured aneurysms. Randomized trials comparing bioactive or hydrogel coated devices with bare coils are ongoing. Other studies were based on registries or case series mainly conducted without control groups. Morbidity, mortality, and initial occlusion rates appear similar for all devices. No clear evidence exists for the superiority of bioactive- or hydrocoils regarding long-term stability. It remains ambiguous whether morbidity and mortality rises with the use of balloons and stents. There is no evidence that routine use of balloons improves treatment durability. Mid-term results of stent-assisted coiling of complex aneurysms appear favorable. There is a lack of studies with a high level of evidence comparing different coiling materials and techniques. Case series and registries were not able to prove the superiority of any device or method.

Craniotomy and Clipping of Intracranial Aneurysm in a Stereoscopic Virtual Reality Environment: Technical Note and Illustrations

Objective: The release of results of the International Subarachnoid Aneurysm Trial (ISAT) in 2003 caused a shift in the paradigm of management of ruptured intracranial aneurysm. The microsurgical clipping cases today are usually aneurysms that are not suitable for embolization, at times complex and difficult. We devised an innovative application of operative planning and training for craniotomy and microsurgical clipping of intracranial aneurysm in a stereoscopic virtual reality environment.

International Subarachnoid Aneurysm Trial of Neurosurgical Clipping Versus Endovascular Coiling

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). 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. 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). 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.

Current trends in endovascular management of intracranial aneurysms (including posterior fossa aneurysms and multiple aneurysms)

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating illness and a major cause of morbidity and mortality.[1] The frequency of aneurysm ranges from 0.4-10%; there is a prevalence of 2.3% in adults without a risk factor for SAH and an annual risk of rupture of 1.9%.[2] Once the aneurysm has bled, there is 15% chance of rebleed in the first few hours, and this is associated with high mortality.[3] Therefore, intracranial aneurysms (IAs) has to be treated surgically or endovascularly. With the publication of the International Subarachnoid Aneurysm Trial (ISAT) results, more and more aneurysms are being treated by endovascular means worldwide.[4] However, each aneurysm should be assessed by an interdisciplinary approach, with the aim being to choose the best option for each patient. Advanced techniques in endovascular therapy have made this modality relatively safe and as effective as surgery in experienced hands.