Author(s):Author(s): Johnston, S Claiborne MD, PhD; Dowd, Christopher F. MD; Johnston, S Claiborne MD, PhD; Dowd, Christopher F. MD; Higashida, Randall T. MD; Lawton, Michael T. MD; Duckwiler, Gary R. MD; Higashida, Randall T. MD; Lawton, Michael T. MD; Duckwiler, Gary R. MD; Gress, Daryl R. MD; for the CARAT Investigators.Gress, Daryl R. MD; for the CARAT Investigators.

Issue: Stroke, Volume 39(1), January 2008, pp 120-125.Issue: Stroke, Volume 39(1), January 2008, pp 120-125. Publisher:© 2008 Publisher:© 2008

American Heart Association, Inc.American Heart Association, Inc.

IntroductionIntroduction

-The primary purpose of intracranial aneurysm treatment is to The primary purpose of intracranial aneurysm treatment is to prevent rupture. prevent rupture.

- Risk factors for rupture after aneurysm treatment have not been - Risk factors for rupture after aneurysm treatment have not been clearly established, and the need to completely occlude aneurysms clearly established, and the need to completely occlude aneurysms is debated. is debated.

- Delayed rerupture is rare after a ruptured intracranial aneurysm is - Delayed rerupture is rare after a ruptured intracranial aneurysm is treated with either coil embolization or surgical clipping.treated with either coil embolization or surgical clipping.

- Early rerupture of treated aneurysms occurs more frequently and - Early rerupture of treated aneurysms occurs more frequently and

has major consequenceshas major consequences..

- In the Cerebral Aneurysm Rerupture After Treatment (CARAT) - In the Cerebral Aneurysm Rerupture After Treatment (CARAT) study, the overall risk of rerupture in the first year after treatment study, the overall risk of rerupture in the first year after treatment is 1.8%. is 1.8%.

- Similarly, the International Subarachnoid Aneurysm Treatment - Similarly, the International Subarachnoid Aneurysm Treatment (ISAT) found a 1.7% risk of rerupture in the first year.(ISAT) found a 1.7% risk of rerupture in the first year.

- Predictors of rerupture after aneurysm treatment have not been - Predictors of rerupture after aneurysm treatment have not been carefully studied. As most of these studies have generally not carefully studied. As most of these studies have generally not been controlled and follow-up has been variable.been controlled and follow-up has been variable.

- This study sought to identify risk factors for rerupture after - This study sought to identify risk factors for rerupture after treatment of intracranial aneurysms, paying particular attention to treatment of intracranial aneurysms, paying particular attention to degree of aneurysm occlusion, using data from CARATdegree of aneurysm occlusion, using data from CARAT, ,

Methods Methods

The Cerebral Aneurysm Rerupture After Treatment (CARAT) study The Cerebral Aneurysm Rerupture After Treatment (CARAT) study

An ambidirectional cohort study of 1010 patients treated with coil An ambidirectional cohort study of 1010 patients treated with coil embolization or surgical clipping.embolization or surgical clipping.

Patients were treated at 9 hospitals in 8 high-volume centers in Patients were treated at 9 hospitals in 8 high-volume centers in the United States from1st of Jan 1996 to end of December 1998. the United States from1st of Jan 1996 to end of December 1998.

Patients were followed for up to 9 years to determine whether Patients were followed for up to 9 years to determine whether delayed rerupture of treated aneurysms .delayed rerupture of treated aneurysms .

Inclusion criteria: Inclusion criteria:

subarachnoid hemorrhage due to rupture of a saccular subarachnoid hemorrhage due to rupture of a saccular intracranial aneurysm and a coil or clip was deployed in an intracranial aneurysm and a coil or clip was deployed in an attempt to treat the index aneurysmattempt to treat the index aneurysm. .

Exclusion criteria:Exclusion criteria:

- Patients were younger than 18 years at follow-up. - Patients were younger than 18 years at follow-up.

- An intracranial arteriovenous malformation or fistula was - An intracranial arteriovenous malformation or fistula was present.present.

- Vessel occlusion was used to treat the aneurysm.- Vessel occlusion was used to treat the aneurysm.

- An endovascular balloon was used for embolization. - An endovascular balloon was used for embolization.

- The patient did not have a US Social Security number. - The patient did not have a US Social Security number.

- Those without information on degree of aneurysm occlusion - Those without information on degree of aneurysm occlusion after treatment (n=9). after treatment (n=9).

- Any aneurysm considered a possible source of the initial - Any aneurysm considered a possible source of the initial subarachnoid hemorrhage and treated during the first procedure subarachnoid hemorrhage and treated during the first procedure was defined as an index aneurysm. was defined as an index aneurysm.

- For coiled patients, postprocedural angiography was the source - For coiled patients, postprocedural angiography was the source of the Degree of aneurysm occlusion. of the Degree of aneurysm occlusion.

- For clipped patients, angiography was used when available; - For clipped patients, angiography was used when available; otherwise, the operative report was used. otherwise, the operative report was used.

- The following scheme was used to convert descriptive terms to - The following scheme was used to convert descriptive terms to categories of occlusion: categories of occlusion: Complete occlusion, Complete occlusion, 100%100% Small residual neck, Small residual neck, 91% to 99%91% to 99% Residual neck, Residual neck, 70% to 90%70% to 90% Partial occlusion (residual aneurysm), Partial occlusion (residual aneurysm), 1% to 69% 1% to 69% Not occluded, Not occluded, 0% 0%

ResultsResults

-Overall, of 1001 included patients index aneurysms were: Overall, of 1001 included patients index aneurysms were:

completely occluded after the first intervention in 760 (75.9%) completely occluded after the first intervention in 760 (75.9%) 91% to 99% occluded in 173 (17.3%) 91% to 99% occluded in 173 (17.3%) 70% to 90% occluded in 51 (5.1%) 70% to 90% occluded in 51 (5.1%) <70% occluded in 17 (1.7%) <70% occluded in 17 (1.7%)

- Rates of total occlusion were greater in patients treated with - Rates of total occlusion were greater in patients treated with clipping (646 of 706, 92%) than with coiling (114 of 295, 39%; clipping (646 of 706, 92%) than with coiling (114 of 295, 39%; PP<0.0001). <0.0001).

- Patients with complete aneurysm occlusion (compared with - Patients with complete aneurysm occlusion (compared with those with partial aneurysm occlusion) were:those with partial aneurysm occlusion) were: younger younger less likely to have chronic obstructive pulmonary disease, less likely to have chronic obstructive pulmonary disease, less likely to have posterior circulation aneurysms. less likely to have posterior circulation aneurysms.

-During a mean of 3.6 years follow-up (median 4.4 years, range 0 During a mean of 3.6 years follow-up (median 4.4 years, range 0 to 9.6 years), there were 19 nonprocedural reruptures (overall risk to 9.6 years), there were 19 nonprocedural reruptures (overall risk ignoring loss to follow-up, 1.9%). ignoring loss to follow-up, 1.9%).

- The median time to rerupture was 3 days (range 1 day to 1.1 - The median time to rerupture was 3 days (range 1 day to 1.1 year). In Kaplan–Meier analysis, the risk of rupture was 2.2% in the year). In Kaplan–Meier analysis, the risk of rupture was 2.2% in the first year, 0.2% in the second year, and 0% thereafter. first year, 0.2% in the second year, and 0% thereafter.

- Rerupture resulted in death within 1 month in 58% of reruptures.- Rerupture resulted in death within 1 month in 58% of reruptures.

- The degree of aneurysm occlusion after treatment was strongly - The degree of aneurysm occlusion after treatment was strongly associated with risk of rerupture, cumulative risk was: associated with risk of rerupture, cumulative risk was:

1.1% for complete occlusion, 1.1% for complete occlusion, 2.9% for 91% to 99% occlusion, 2.9% for 91% to 99% occlusion, 5.9% for 70% to 90%, 5.9% for 70% to 90%, 17.6% for <70%; 17.6% for <70%; PP<0.0001 by log-rank test<0.0001 by log-rank test

- Overall, 17 of 19 reruptures occurred in the first month after - Overall, 17 of 19 reruptures occurred in the first month after treatment. treatment.

- Among those with rerupture, degree of aneurysm occlusion was - Among those with rerupture, degree of aneurysm occlusion was not associated with risk of death (not associated with risk of death (PP=0.22).=0.22).

- Risk of rerupture tended to be greater after coil embolization - Risk of rerupture tended to be greater after coil embolization compared with surgical clipping, However, the difference was not compared with surgical clipping, However, the difference was not significant (hazard ratio, 1.09; 95% CI, 0.32 to 3.69; significant (hazard ratio, 1.09; 95% CI, 0.32 to 3.69; PP=0.89).=0.89).

- A history of peripheral vascular disease was the only other - A history of peripheral vascular disease was the only other patient or aneurysm characteristic that independently predicted patient or aneurysm characteristic that independently predicted rerupture rerupture

- There were no reruptures after retreatment. - There were no reruptures after retreatment.

- The association between degree of aneurysm occlusion - The association between degree of aneurysm occlusion remained a strong predictor of risk of rerupture in an analysis remained a strong predictor of risk of rerupture in an analysis without censoring at time of retreatment (without censoring at time of retreatment (PP<0.001). <0.001).

- There was no evidence that attempting more complete aneurysm - There was no evidence that attempting more complete aneurysm occlusion was associated with a greater risk of complications in occlusion was associated with a greater risk of complications in the index procedure. Specifically, among those treated with the index procedure. Specifically, among those treated with clipping. clipping.

- There was no association with degree of occlusion and either - There was no association with degree of occlusion and either perioperative disability/mortality (perioperative disability/mortality (PP=0.31) or intraprocedural =0.31) or intraprocedural rupture (rupture (PP=0.77). =0.77).

- For those treated with coiling results of degree of occlusion and - For those treated with coiling results of degree of occlusion and risk of intraprocedural rupture were similar (risk of intraprocedural rupture were similar (PP=0.38).=0.38).

- there was an insignificant trend toward greater risk of new - there was an insignificant trend toward greater risk of new disability with greater degrees of occlusion achieved during the disability with greater degrees of occlusion achieved during the index treatment (index treatment (PP=0.07 =0.07

DiscussionDiscussion

-This study found that early rerupture was an infrequent but This study found that early rerupture was an infrequent but important early complication of treatment, particularly among important early complication of treatment, particularly among those treated with coil embolization. those treated with coil embolization. - Half of reruptures occurred during the first 3 days after - Half of reruptures occurred during the first 3 days after treatment. treatment.

- Incomplete occlusion of the aneurysm was a strong predictor of - Incomplete occlusion of the aneurysm was a strong predictor of risk of rerupture. risk of rerupture.

- The risk of rupture in aneurysms that were <70% occluded was - The risk of rupture in aneurysms that were <70% occluded was 24.5% in the first year, similar to rerupture rates in prior studies of 24.5% in the first year, similar to rerupture rates in prior studies of untreated ruptured aneuruntreated ruptured aneurysms.ysms.

- There is no evidence to suggest that attempting complete - There is no evidence to suggest that attempting complete occlusion was associated with increased procedural risk occlusion was associated with increased procedural risk

-Complete aneurysm occlusion after initial treatment did not Complete aneurysm occlusion after initial treatment did not guarantee that rerupture would not occur, though the risk of guarantee that rerupture would not occur, though the risk of rerupture was only 1.1% in this group with all events occurring rerupture was only 1.1% in this group with all events occurring during the first year. during the first year.

- Follow-up imaging in all patients with treated aneurysms is very - Follow-up imaging in all patients with treated aneurysms is very important, particularly during the first year after initial treatment. important, particularly during the first year after initial treatment.

- The risk of rerupture and the inconvenience and risk of - The risk of rerupture and the inconvenience and risk of retreatment should be considered when consenting patients for retreatment should be considered when consenting patients for treatment. treatment.

- Eighteen of the 19 reruptures in this study occurred during the - Eighteen of the 19 reruptures in this study occurred during the first year after treatment, with half occurring during the first 3 first year after treatment, with half occurring during the first 3 days. days.

- After 1 year, the annual risk of rerupture was 0.11% in patients - After 1 year, the annual risk of rerupture was 0.11% in patients treated with coil embolization, and there were no reruptures treated with coil embolization, and there were no reruptures among clipped patients. among clipped patients.

-The most obvious limitation of this study is the lack of The most obvious limitation of this study is the lack of standardization in assessment of degree of aneurysm occlusion. standardization in assessment of degree of aneurysm occlusion.

- Although angiography was routine immediately after coil - Although angiography was routine immediately after coil embolization, it was performed only in a subset of patients after embolization, it was performed only in a subset of patients after clipping, and degree of occlusion was derived from operative clipping, and degree of occlusion was derived from operative reports in these instances.reports in these instances.

- Though this was a large study, the actual number of patients - Though this was a large study, the actual number of patients with rerupture was small, thus limiting the power of the study, this with rerupture was small, thus limiting the power of the study, this may have impacted the ability to identify other factors associated may have impacted the ability to identify other factors associated with rerupture, including larger aneurysm size, which has been with rerupture, including larger aneurysm size, which has been associated with risk of rerupture before treatment associated with risk of rerupture before treatment

- On the other hand, the study evaluated multiple factors as - On the other hand, the study evaluated multiple factors as potential confounders, so the association of aneurysm rerupture potential confounders, so the association of aneurysm rerupture with peripheral vascular disease could have been due to chance with peripheral vascular disease could have been due to chance and requires independent confirmation. and requires independent confirmation.

Conclusions:-Conclusions:-Degree of aneurysm occlusion after the initial treatment is a Degree of aneurysm occlusion after the initial treatment is a strong predictor of the risk of subsequent rupture in patients strong predictor of the risk of subsequent rupture in patients presenting with subarachnoid hemorrhage, which justifies presenting with subarachnoid hemorrhage, which justifies attempts to completely occlude aneurysms.attempts to completely occlude aneurysms.