Abstract & Commentary
Source: ISAT Collaborative Group. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomized trial. Lancet. 2002;360:1267-1274.
Neurosurgical clipping has long been the mainstay of intracranial aneurysm treatment. Such therapy involves a large craniotomy, complex microsurgical dissection, and considerable up-front morbidity for the patient. In contrast, endovascular treatment with Guglielmi detachable coils (GDC) can be accomplished via transfemoral angiography and spares the patient a major neurosurgical procedure. Coiling further offers the prospect of treating aneurysms difficult or impossible for surgeons to access, such as at the basilar artery tip. Despite these advantages, neurosurgical clipping remains the more widely available established therapy, often relegating coiling to patients in poor neurological or medical condition, such as the elderly with Hunt and Hess grade III or IV subarachnoid hemorrhage (SAH). Such a practice is currently justifiable, as long-term durability data for GDC treatment (available since 1995) are only now starting to accrue. Young patients able to more easily tolerate craniotomy might be better clipped to avoid possible eventual aneurysm recurrence, which requires repeat treatment. Worse yet, they may suffer clinical rebleeding from an inadequately treated lesion. Aneurysm anatomy, such as a high dome to neck ratio or involvement of a parent vessel wall, may push treatment in one direction or another, but in many cases it is referral patterns rather than science that dictates how patients are treated. It is in the setting of this very controversial climate that the ISAT trial has been conducted.
The ISAT trial enrolled 2143 patients, primarily in Britain, with ruptured intracranial aneurysms and randomly assigned them to neurosurgical clipping (n = 1070) or GDC coils (n = 1073). Because interim analysis demonstrated a striking difference between these groups in favor of coiling, the trial was stopped short of its planned goal of 2500 patients. At 1-year follow-up, the risk of death or significant disability (Rankin score 3-6) was 30.6% in the neurosurgical group compared to 23.7% in the endovascular group. This was a 6.9% absolute and 22.6% relative risk reduction in favor of coiling. Many patients were screened but excluded from the study. Of 9559 patients initially assessed, only 20% were actually enrolled. In the remainder, a decision was made that clipping or coiling was clearly more favorable and thus the patient could not be subjected to a random treatment choice. Considerable bias could have been introduced into the study during this screening process.
The ISAT patients are not completely representative of the SAH population at large. Eighty-eight percent were of good clinical status (Hunt and Hess grade I or II), 93% of aneurysms were 10 mm or smaller in diameter, and 97% were in the anterior circulation. The generalizability of ISAT data is therefore limited. There was a significant occurrence of post-treatment rebleeding. This was found in 2.4% (26/1048) of endovascular cases compared with 1.0% (10/994) of clipped patients. While these results clearly favor neurosurgery, such an incidence of incompletely treated aneurysms is unusual for either therapy in experienced hands. There were additionally 11 cases (6 coiled, 5 clipped) that re-bled despite indications that complete aneurysm obliteration had been achieved. Such results have led some to question the skill of some of the investigators in the study, raising doubts about the validity of the study in general.
These data are unlikely to put this raging debate to rest, but certainly add another nail into the coffin of neurosurgical clipping. Although nonrandomized and retrospective, data from UCSF1 indicate that similar morbidity, mortality, and cost-effectiveness differences in favor of coiling may be demonstrated in US centers. Despite these data, some will continue to argue that outcomes depend not only upon differences in these techniques but also upon the relative skill of the neurosurgical or endovascular operator. Coils, say the neurosurgeons, lack a lengthy track record of durability, whereas a clip is a guarantee against recurrence. We are currently engaged in a good old-fashioned turf war. With a new breed of "endovascular neurosurgeons," however, the cranial drill and the femoral catheter will not be in competition but rather options within a particular individual’s armamentarium.
Additional questions remain, such as how to treat unruptured incidentally diagnosed aneurysms. Extrapolation from the ISAT data is helpful, but it is not completely accurate to consider ruptured and unruptured aneurysms as one and the same. The best answer might come from neurologists involved in stroke and critical care. When asked, "How would you wish to be treated should you be diagnosed with an aneurysm?" no one that I know of has ever opted for the knife.
The gulf between craniotomy and endovascular therapy is furthermore likely to continue to widen in favor of coils. The continual development of new types of catheters, coils, balloons, and stents has already pushed the endovascular envelope far beyond the ISAT trial and will continue to do so in the coming years. — Alan Z. Segal
Dr. Segal, Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Presbyterian Hospital, is Assistant Editor of Neurology Alert.
1. Johnston, et al. Stroke. 2002;33:2536-2544.