International Subarachnoid Aneurysm Trial II

The International Subarachnoid Aneurysm Trial (ISAT) was a turning point in modern
neurosurgical history (1). The trial showed that for 2143 subarachnoid hemorrhage
(SAH)patients eligible for both surgery and endovascular coiling, randomized allocation to
coiling was associated with better one year clinical outcomes, defined as survival without
dependency (absolute risk reduction (ARR) of 7.4% (95%CI; 3.6 - 11.2, p=0.0001). Because ISAT
was a positive pragmatic trial, the interpretation of the trial results was that coiling
should be adopted as the first-line treatment for ruptured lesions, for patients with the
types of aneurysms included in ISAT, of which the great majority were small (≥10 mm) anterior
circulation aneurysms.

Although ISAT was well-designed, conducted, and reported, trial results were not always
properly interpreted, and endovascular coiling was perhaps inappropriately extrapolated
beyond what ISAT demonstrated. Endovascular treatment for ruptured aneurysms has now become
first-line treatment in many centers (2), which may be appropriate for small, anterior
circulation lesions, but there is no evidence to support this practice for the wide spectrum
of non-ISAT patients and aneurysms. A recent pre-randomized study of coiling as
first-intention (3)showed better results for those ruptured aneurysms felt to be readily
coilable; however, the optimal management of more difficult-to-coil ruptured aneurysms
remains unclear.

Further compounding the problem are the concerns that aneurysm coiling may not be as durable
in the long-term as surgical clipping, leading many neurosurgeons to continue to clip most
ruptured aneurysms in spite of ISAT results.

Proponents of endovascular treatment sometimes justify this extrapolation of ISAT results on
the basis of improved catheter and coil technology, although this has never been
demonstrated. However, the addition of stents and flow-diverters, which were not tested in
ISAT, may increase endovascular treatment risks, especially when combined with dual
anti-platelet agents. The introduction of these devices allowed for the expansion of
indications of EVT to include wide-necked aneurysms, lesions which would not have been
included in ISAT. The wider spectrum of patients and aneurysms now considered for EVT may not
all experience the same degree of benefit as seen in the original ISAT trial (4). Considering
the relatively small ARR of 7.4% favouring coiling, when the additional risks due to stents
are included, the balance may have tipped to favour surgical clipping.

These new questions deserve formal study in the context of a randomized clinical trial.

Inclusion Criteria:

- Patients at least 18 years of age

- At least one documented, intradural, intracranial aneurysm, ruptured within last 30
days

- SAH WFNS grade 4 or less

- The patient and aneurysm are considered appropriate for either surgical or
endovascular treatment by the treating team

Exclusion Criteria:

- Patients with absolute contraindications administration of contrast material (any
type)

- Patients with AVM-associated aneurysms

- Aneurysm located at basilar apex