Elsevier

The Lancet

Volume 360, Issue 9342, 26 October 2002, Pages 1267-1274
The Lancet

Articles
International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial

https://doi.org/10.1016/S0140-6736(02)11314-6Get rights and content

Summary

Background

Endovascular detachable coil treatment is being increasingly used as an alternative to craniotomy and clipping for some ruptured intracranial aneurysms, although the relative benefits of these two approaches have yet to be established. We undertook a randomised, multicentre trial to compare the safety and efficacy of endovascular coiling with standard neurosurgical clipping for such aneurysms judged to be suitable for both treatments.

Methods

We enrolled 2143 patients with ruptured intracranial aneurysms and randomly assigned them to neurosurgical clipping (n=1070) or endovascular treatment by detachable platinum coils (n=1073). Clinical outcomes were assessed at 2 months and at 1 year with interim ascertainment of rebleeds and death. The primary outcome was the proportion of patients with a modified Rankin scale score of 3–6 (dependency or death) at 1 year. Trial recruitment was stopped by the steering committee after a planned interim analysis. Analysis was per protocol.

Findings

190 of 801 (23·7%) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 (30·6%) allocated neurosurgical treatment (p=0·0019). The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22·6% (95% Cl 8·9–34·2) and 6–9% (2·5–11·3), respectively. The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 and zero per 1081 patient-years for patients allocated endovascular and neurosurgical treatment, respectively.

Interpretation

In patients with a ruptured intracranial aneurysm, for which endovascular coiling and neurosurgical clipping are therapeutic options, the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling. The data available to date suggest that the long-term risks of further bleeding from the treated aneurysm are low with either therapy, although somewhat more frequent with endovascular coiling.

Introduction

Rupture of an intracranial aneurysm causing Subarachnoid haemorrhage (SAH) occurs with a frequency of between six and eight per 100 000 in most western populations.1 Neurosurgical intervention to clip the aneurysm and prevent further bleeding carries both risks and benefits. In the 1960s, McKissock and colleagues published a series of prospective randomised trials,2, 3, 4 which showed that the benefits of surgery outweighed the risks in some circumstances (depending on the location of the aneurysm).

Since then, there have been incremental reductions in the risk of surgery for ruptured intracranial aneurysms. These risk reductions have been achieved by advances in many aspects of management, including the introduction of the operating microscope, the development of better microsurgical techniques and instruments, advances in anaesthetic and intensive-care management, improved diagnostic facilities, and the development of vascular neurosurgery as a subspecialty. Nonetheless, even with these advances, relatively few patients return to a normal lifestyle after SAH, and many have persistent disabling neurological or cognitive defects.5 In 1990, a detachable platinum coil device, the Guglielmi detachable coil (GDC; Boston Scientific/Target Therapeutics, Freemont, CA, USA)6 was introduced into clinical use. It was first used as an investigational device in the USA, and then introduced in Europe in 1992 and was approved by the US Food and Drugs Administration in 1995. This device allowed the development of endovascular techniques for the occlusion of intracranial aneurysms, which offered the prospect of reducing the risk of further rupture without the need for craniotomy. Since 1995, endovascular coiling has become widely used in patients with ruptured and unruptured intracranial aneurysms.7, 8, 9

The introduction of an alternative to neurosurgical clipping raised the questions of how, when, and in whom endovascular treatment should be used. The frequency of use of this technique varies widely around the world and there is an urgent need for high quality evidence to establish the safety and efficacy of endovascular treatment compared with neurosurgical treatment, and to determine which treatment provides the best outcomes for patients. Only one small randomised trial of 109 patients with a ruptured intracranial aneurysm comparing the detachable coil technique with neurosurgical clipping has been published to date.10, 11

This paper describes the protocol, methods, and primary outcome results of the International Subarachnoid Aneurysm Trial (ISAT). ISAT is a multicentre, randomised clinical trial, which compares a policy of neurosurgical clipping with a policy of endovascular treatment with detachable platinum coils in patients with ruptured intracranial aneurysms considered suitable for either treatment.

Section snippets

Aims and objectives

The aim of ISAT was to compare the safety and efficacy of a policy of endovascular treatment of ruptured intracranial aneurysms versus a policy of conventional neurosurgical treatment in patients who were suitable for either treatment. The primary objective was to determine whether a policy of endovascular treatment compared with a policy of neurosurgical treatment reduced the proportion of patients dependent or dead, as defined by modified Rankin scale 3–6 (panel), at one year by 25%.12, 13, 14

Results

The Data Monitoring Committee met on April 29, 2002, to consider the results of a planned interim analysis. They unanimously agreed that the trial steering committee be advised of the interim results. The steering committee met on May 2, 2002, and decided that recruitment should stop, but that follow-up must continue. Recruitment ceased immediately.

The proportion of all aneurysmal SAH patients entered in the trial varied widely, between 1% and 44%, among the centres. 16 centres were able to

Discussion

The results show that endovascular intervention with detachable platinum coils in patients with ruptured intracranial aneurysms can improve the chances of independent survival compared with neurosurgical intervention to clip the neck of the aneurysm. At 1 year, the relative risk of dependence or death was reduced by 22·6%, with an absolute risk reduction of 6·9%. This result, achieving the primary ISAT objective, led to trial recruitment being stopped early by the steering committee.

The results

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