Journal Club

Could Late Rebleeding Overturn the Superiority of Cranial Aneurysm Coil Embolization over Clip Ligation Seen in the International Subarachnoid Aneurysm Trial?

Mitchell P, Kerr R, Mendelow AD, et al.
J Neurosurg 2008;108:437–42

Background: The International Subarachnoid Aneurysm Trial (ISAT) randomized 2,143 patients to either receive endovascular coil embolization or surgical clipping of acutely ruptured aneurysms. Unfavorable outcomes at 1 year after treatment were observed in 30.9% of cases randomized to clip ligation and 23.5% of cases that were treated by coil embolization. However, as late rebleeding occurs more often in patients treated by coil embolization (0.152%/year in ISAT, up to 0.3%/year in the literature vs. 0.03% for surgery), the question occurs whether at a younger age and a longer life expectancy the superiority of the initial postinterventional results may be overturned by the rate of late rebleeding. To put it simple: the basic question is whether under a certain age, clip placement should be favored over coiling.

Methods: All calculations were based on the ISAT data of the 2,143 patients enrolled in this study. A subgroup analysis of initial poor outcomes for different ages was presented. Different but constant rebleeding risks of 0–0.3% were applied to the coil group to calculate life expectancy at different ages of the primary event while the clip group was calculated with a late rebleeding risk of 0.03%. This analysis was set into the context of the initial results immediately following intervention.

Results: The difference between poor outcome rates of coiled versus clipped aneurysms is very small in patients under the age of 40. In addition, because of the longer life expectancy in this younger group, the higher rate of rebleeding after coiling favors clip ligation over coil placement in this age group. In patients over the age of 70, outcomes after coiling are worse than after clipping, whereas in the age group of 40–70 year old, coiling may gain up to 3 years of patient life after a subarachnoid hemorrhage (SAH) compared to clipping.

Conclusion: When treating ruptured cerebral aneurysms, the advantage of coiling an aneurysm over clipping it cannot be assumed for patients younger than 40 years. Here the difference in the safety of both procedures is small, and the better long-term protection from SAH after clip ligation may give this treatment an advantage in life expectancy for patients < 40 years of age.

Comment

For the past 5 years, ISAT has been the best friend of the interventional neuroradiologist. Although there are some well-known and overtly discussed points of criticism, it is a very powerful and important study to demonstrate that in ruptured aneurysms deemed treatable both with coils and clips, the surgical procedure leads to higher rates of poor outcome. However, clips have proven to be more efficient in preventing late rebleeds (0.03% vs. 0.152%/patient year). This led to the question, of which method is better in the long term. The present study revealed, in a post hoc analysis of patients that were stratified according to their age, a fact that common sense feared already a while: young patients seem to profit from clips more than from coils.

When looking at the ten largest studies since 1999 evaluating the percentage of patients harboring a residual aneurysm after coil treatment, values between 5% and 20% are most often encountered, likewise recanalization rates after coiling are reported to be present in 15–35% of patients. Still the rebleeding rate is, in comparison to these results, surprisingly low with 0.1–0.3%/year. Is this rebleeding rate constant? Or will it increase over time given the fact that some aneurysms seem not to be stable and progressively recanalize? Or will at one time a healing process occur that may reduce the risk of very late rebleedings? What about the efficacy (and the dangers) of retreatments (that in the literature are performed in 5–13% of patients)? New materials have been introduced allowing higher packing densities and increased host responses, learning curves had to be mastered, the widespread use of three-dimensional roadmapping, and the introduction of new thrombolytic agents have dramatically changed the neurointerventionalist’s life and improved the patient’s prognosis. Mitchell et al. from the ISAT study must be congratulated on calculating the cutoff age where the potential risks of rebleeding with its associated morbidity and mortality may outweigh the better primary outcome after the intervention. However, these calculations are based on a constant rebleeding risk for which no supporting data is available, since it does neither take the progressive recanalization rates nor the improved material, nor the risks and benefits of retreatments into consideration.

The authors report that the difference between poor outcome rates after clipping and coiling is much smaller for young people than for the whole population. This has two implications, of which only one is overtly stated by the authors, i.e., clipping may be beneficial to young patients given the higher rebleeding rate after coil embolization. However, the second implication that can be deduced from these results is that coiling has an even larger than previously estimated advantage in patients above the age of 40. In fact, in the age group of 50- to 60-year-old patients, poor outcome results are 20.2% for patients who underwent coiling and 33.4% of patients who were clipped. When this value is correlated with the life expectancy, the authors of this study state that this results in up to 3 years of life gained by coiling over clipping. Interestingly, this effect wears off in the population of patients being older than 70 years; here, clipping has a slight advantage over coiling.

What does this article tell us for our daily routine? To put it simple: in those patients where both the neurosurgeon and the neuroradiologist feel comfortable treating the ruptured aneurysm, clipping should be favored over coiling when the patient is below the age of 40 or above the age of 70.

What does it tell us for potential future research studies? Since neurosurgical procedures did not improve after ISAT had been discontinued, endovascular methods, however, did, coiling will remain the standard of treatment for patients older than 40 and younger than 70. Within the subset of patients below 40 and above 70, new comparative studies should evaluate the clinical benefits of the neuroradiologist’s improved armamentarium.

(submitted April 10, 2008)

Timo Krings, Franz J. Hans, Aachen, Germany