Elsevier

The Lancet

Volume 366, Issue 9488, 3–9 September 2005, Pages 809-817
The Lancet

Articles
International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion

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Summary

Background

Two types of treatment are being used for patients with ruptured intracranial aneurysms: endovascular detachable-coil treatment or craniotomy and clipping. We undertook a randomised, multicentre trial to compare these treatments in patients who were suitable for either treatment because the relative safety and efficacy of these approaches had not been established. Here we present clinical outcomes 1 year after treatment.

Methods

2143 patients with ruptured intracranial aneurysms, who were admitted to 42 neurosurgical centres, mainly in the UK and Europe, took part in the trial. They were randomly assigned to neurosurgical clipping (n=1070) or endovascular coiling (n=1073). The primary outcome was death or dependence at 1 year (defined by a modified Rankin scale of 3–6). Secondary outcomes included rebleeding from the treated aneurysm and risk of seizures. Long-term follow up continues. Analysis was in accordance with the randomised treatment.

Findings

We report the 1-year outcomes for 1063 of 1073 patients allocated to endovascular treatment, and 1055 of 1070 patients allocated to neurosurgical treatment. 250 (23·5%) of 1063 patients allocated to endovascular treatment were dead or dependent at 1 year, compared with 326 (30·9%) of 1055 patients allocated to neurosurgery, an absolute risk reduction of 7·4% (95% CI 3·6–11·2, p=0·0001). The early survival advantage was maintained for up to 7 years and was significant (log rank p=0·03). The risk of epilepsy was substantially lower in patients allocated to endovascular treatment, but the risk of late rebleeding was higher.

Interpretation

In patients with ruptured intracranial aneurysms suitable for both treatments, endovascular coiling is more likely to result in independent survival at 1 year than neurosurgical clipping; the survival benefit continues for at least 7 years. The risk of late rebleeding is low, but is more common after endovascular coiling than after neurosurgical clipping.

Introduction

The International Subarachnoid Aneurysm Trial (ISAT), a randomised trial comparing neurosurgical clipping with endovascular coiling in patients with ruptured intracranial aneurysms, closed recruitment after an interim analysis showed a benefit of endovascular treatment on the primary outcome: death or dependency at 1 year. Our first report1 of the interim results used the outcome data available at the time of that analysis. These data were incomplete because 1-year follow-up was available for only 1594 of the 2143 patients enrolled. However, the difference between the two treatments was significant: endovascular coiling was associated with an absolute reduction in the risk of death or dependence at 1 year of 6·9% (a relative risk reduction of 22·6%, p<0·001) compared with neurosurgical clipping.1 The 1-year data are now complete and we report here the primary outcome at 1 year for all patients combined and subdivided by the prespecified subgroups.2 We also report results for secondary outcomes: epilepsy, rebleeding from the treated aneurysm, deaths during medium-term follow-up (with survival curves to 7 years), and the findings on follow-up angiography. Patients were eligible for enrolment into ISAT if the responsible neurosurgeon and neuroradiologist were uncertain about the best treatment. If there was insufficient uncertainty, the patient could not be randomised.3

Section snippets

Patients

The trial protocol and methods, including the randomisation and minimisation criteria, recruiting centres, patient demographics and aneurysm characteristics, have already been published.1, 2 Eligible patients had subarachnoid haemorrhage due to intracranial aneurysm, suitable for either endovascular or neurosurgical treatment. These subgroups were prespecified: World Federation of Neurosurgical Societies (WFNS) grade at randomisation, age groups by decade (<40, 40–49, 50–59, 60–69, ⩾70 years),

Results

Baseline characteristics of the enrolled patients were similar between the treatment groups and have been detailed.1 88% of patients were in good clinical grade (WFNS 1 or 2) at the time of enrolment, 95% of the aneurysms were in the anterior cerebral circulation, and 90% were smaller than 10 mm. The mean follow-up is now 4 years, with 6542 patient years of follow-up available after 1 year.

1073 and 1070 patients were randomised to endovascular coiling or neurosurgical clipping, respectively. Of

Discussion

The final 1-year results presented in this paper reinforce our preliminary findings. Endovascular coiling, compared with neurosurgical clipping, for ruptured intracranial aneurysms that were anatomically suitable for either procedure leads to a significant reduction in the relative risk of death or dependency of 23·9% (12·4–33·9). This equates to an absolute risk reduction of 7·4% (3·6–11·2), which is equivalent to 74 patients avoiding death or dependency at 1 year for every 1000 patients

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