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Summary of The International Subarachnoid Aneurysm
Trial Summary (ISAT)
What is the International Subarachnoid Aneurysm
Trial?
The International Subarachnoid Aneurysm Trial -- or
ISAT -- is the only multi-center, prospective randomized
trial comparing the safety and efficacy of endovascular
coil treatment and surgical clipping for the treatment
of ruptured brain aneurysms1. The primary objective
of ISAT was to determine whether endovascular treatment
compared with neurosurgical treatment reduced the proportion
of patients dependent or dead, defined by a modified
Rankin score of 3-6.
What types of patients were included in the ISAT?
ISAT's primary inclusion criterion was patients with
ruptured aneurysms who were deemed equally suited for
either neurosurgical clipping or endovascular coil treatment.
Most patients were not deemed equally suitable for both
treatment options and were therefore not randomized.
Most of the 2,143 patients randomized into the trial
had good-grade (88% in World Federation of Neurosurgical
Societies (WFNS) grades I and II), small anterior circulation
aneurysms (92 percent less than 11 mm in size).
What were the primary results of the ISAT?
The study found that, in patients equally suited for
both treatment options, endovascular coil treatment
produces substantially better patient outcomes than
surgery in terms of survival free of disability at one
year. The relative risk of death or significant disability
at one year for patients treated with coils was 22.6%
lower than in surgically-treated patients, an absolute
risk reduction of 6.9%2. A one-year primary
outcome point was chosen to ensure that the likelihood
and effects of any subsequent procedures and the occurrence
of early rebleeding would be taken into account.
What are the implications for the treatment of patients
with ruptured aneurysms?
The ISAT findings are relevant to the types of patients
randomized into the trial - good-grade patients with
small anterior circulation aneurysms. The results suggest
that these patients may be candidates for coiling and
should receive an endovascular consultation as part
of the treatment protocol. For patients that do not
fit this profile, treatment decisions should be based
on other research.
What were the rebleed rates during the first year
for the two procedures?
The risk of rebleeding during the first year was low
in both groups (2.4% for the endovascular group and
1.0% for the surgical group). The effects of rebleeds
have been factored into the one-year finding that the
relative risk of death or significant disability for
endovascular patients was 22.6 percent lower than for
surgical patients.
What are the long-term rebleed rates for the two
procedures?
While complete long-term data from the ISAT is not yet
available, significant follow-up data has been collected
because patients were enrolled in the trial as early
as 1997. There was no statistical difference between
the post one-year rebleed rates in the two patient groups.
The risk of rebleeding after one year was two per 1,276
follow-up years for endovascular patients and zero per
1,081 follow-up years for surgical patients. Patients
will be followed through at least 2007.
How do the ISAT centers compare to hospitals in
the United States?
ISAT centers, which treat between 60 and 200 ruptured
aneurysm cases per year, and high-volume centers in
the United States have reported similar surgical management
mortality rates in the treatment of ruptured aneurysms3.
However, most ruptured aneurysm patients in the United
States are not treated at high-volume centers. Typical
ruptured aneurysm patients are treated at hospitals
that admit fewer than 18 ruptured aneurysm cases a year4.
In fact, 75 percent of US SAH patients present at hospitals
that see less than 36 cases a year. All of the centers
that participated in ISAT had both surgical and endovascular
expertise, whereas more than 75% of ruptured aneurysm
patients in the United States are admitted to hospitals
that do not have an endovascular service available.
How do the ISAT mortality results compare with other
studies?
The surgical management mortality rate reported in ISAT
is similar to that reported in the multicenter, randomized
North American trial of tirilazad. Although there are
some differences in the distribution of clinical grades
in the two trials and in the timing of outcomes assessment,
the tirilazad study does provide a reference point of
surgical outcomes. In the tirilazad study, 9.2% of the
grade I-III patients had died at three-months3. In ISAT,
8.3% and 10.1% of surgically-treated patients were dead
at two months and one-year, respectively. Most other
available research on the surgical treatment of aneurysms
is from case series that are not directly comparable
to ISAT. Randomized trials record the management mortality
of all patients enrolled, including those who cross-over
or rebleed prior to treatment. Self-reported case series
usually do not include these cases and may under-report
bad outcomes5.
How do the ISAT morbidity results compare with other
studies?
Comparison of morbidity data across studies is unreliable
because of the variations in methods of data collection.
ISAT relied on patient-reported outcomes on the modified
Rankin scale. Other studies on the surgical treatment
of aneurysms have relied on physician or third-party
assessment on the Glasgow Outcome Scale5,6.
Will there be more data forthcoming from the ISAT?
The Medical Research Council of Great Britain has granted
funding for ISAT through 2007. Additional data on cost
effectiveness, quality of life, angiographic findings
and rebleed rates will be collected and analyzed for
publication.
How can I learn more about the ISAT study?
More information about study design and results is available
at the ISAT
homepage (http://users.ox.ac.uk/~isat/).
1Molyneux A, Kerr R, Stratton I, Sandercock
P, Clarke M, Shrimpton J, Holman R. International Subarachnoid
Aneurysm Trial (ISAT) of neurosurgical clipping versus
endovascular coiling in 2143 patients with ruptured
intracranial aneurysms: a randomised trial. Lancet.
2002: 360: 1267-74.
2One-year data on 1,888 patients demonstrated
a relative risk reduction of 26.8% in favor of coiling,
an absolute risk reduction of 8.7%. Reference: Kerr
R. The International Subarachnoid Aneurysm Trial: What
have we learned? Presentation at the AANS Satellite
Symposium: State of the Art Treatment for Acute Subarachnoid
Hemorrhage. April 28, 2003.
3Haley EC, Kassell NF, Apperson-Hansen C,
Moles MH, Alves WM. A randomized double-blind, placebo-controlled
trial of tirilazad mesylate in patients with aneurysmal
subarachnoid hemorrhage: a cooperative study in North
America. J Neurosurg. 1997;86: 467-74.
4Cross, DeWitte T et. al. Mortality Following
Subarachnoid Hemorrhage Varies With Hospital Case Volume
in 18 States. To be published.
5Grimes, David A and Schulz, Kenneth F. An
overview of clinical research: the lay of the land.
Lancet. 2002: 359: 57-61.
6Kassell NF, Haley EC, Apperson-Hansen C,
et al. Randomized, double-blind, vehicle-controlled
trial of tirilazad mesylate in patients with aneurysmal
subarachnoid hemorrhage: a cooperative study in Europe,
Australia, and New Zealand. J Neurosurg. 1996;
84: 221-228.
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