Age-Related Complications following Endovascular Treatment of Unruptured Intracranial Aneurysms

BACKGROUND AND PURPOSE: The factors that led us to do the research for this paper was a desire to see if elderly patients did as well as non-elderly patients during endovascular intracranial aneurysm treatment. By doing this research, we could better stratify the most appropriate treatment for each patient with an aneurysm. The purpose of this study was to determine whether the incidence of procedural complications was greater in the elderly, defined as patients older than 65 years of age, compared with nonelderly patients undergoing elective endovascular treatment for intracranial aneurysms. MATERIALS AND METHODS: A retrospective review was performed in patients undergoing elective endovascular treatment of intracranial aneurysms between 2000 and 2010 at 1 institution. “Minor complications” were defined as those resulting in minimal or no loss of function that resolved before dismissal; “major complications” were complications that resulted in loss of function or complications that required a subsequent invasive therapy. Major complications were further stratified into those with and without neurologic disability, defined as an mRS score of >3. T tests and χ2 analyses were used to compare groups. RESULTS: Three hundred fifty-five patients underwent 394 endovascular procedures treating 75 aneurysm recurrences and 319 untreated aneurysms. One hundred eight (30%) were elderly. There was no significant difference in the rate of complications in the elderly compared with the nonelderly (33% versus 26%, respectively; P = .18). Major complications were significantly more prevalent in the elderly than in the nonelderly (17% versus 7.4%, respectively, P = .004). Major complications with neurologic disability were also significantly more prevalent in the elderly compared with the nonelderly (8.2% versus 1.8%, respectively, P = .004). CONCLUSIONS: Major functional complications were markedly more common in the elderly compared with the nonelderly.

E ndovascular treatment with coiling has been established as a mainstay therapy of intracranial aneurysms.2][3][4][5] Although it is the preferred choice of treatment for unruptured intracranial aneurysms in general, it remains unclear whether endovascular coiling should be used in the elderly population.Advanced age has been reported to increase the risk of complications following such procedures as carotid stent placement 6,7 as well as surgical clipping of intracranial aneurysms. 8lderly patients may appear better suited for endovascular therapy than open surgery because they have an increased number of comorbidities compared with younger patients, making them poor surgical candidates. 9,10However, it is not clear whether advanced age alone increases the risk of complications in patients undergoing endovascular aneurysm therapy. 11he purpose of this study was to determine the incidence of complications in patients undergoing elective endovascular therapy for intracranial aneurysm and whether complications were more frequent in elderly patients compared with younger patients.

Materials and Methods
We performed a retrospective review of patients undergoing elective endovascular treatment for all intracranial aneurysms at our institution, a large tertiary referral center, between January 2000 and January 2010, following approval by the Mayo Clinic institutional review board.Elective treatment was defined as treatment for either an unruptured aneurysm or retreatment of a previously treated aneurysm.When deemed necessary to achieve aneurysm obliteration, balloonassisted and stent-assisted coiling was performed.Data collected on each patient included age; sex; number, size and location of aneurysms; presence of symptoms referable to the target aneurysms; comorbidities; type of treatment; treatment outcomes; intraprocedural medications; number of coils used; and procedural complications.
A "complication" was defined as any condition arising within 30 days of the endovascular procedure that necessitated further evaluation or treatment.Complications were stratified into 2 categories, minor and major.A "minor complication" was defined as a complication that resulted in minimal or no loss of function and resolved before dismissal; major complications were complications that resulted in loss of function (temporary or permanent) or complications that required a subsequent invasive therapy."Major complications" were further characterized into 2 categories: complications that resulted in unresolved neurologic deficits at dismissal and complications without neurologic deficits at dismissal.An "unresolved neurologic deficit" in major complications was defined as a neurologic deficit at the time of dismissal that was Ն3 on the mRS. 12,13mRS score was determined by retrospectively evaluating postprocedure neurology examinations."Elderly patients" were defined as those patients older than 65 years of age at the time of treatment.[16]

Endovascular Treatment
Patients were treated under general anesthesia.Typically, a 6F guiding catheter (Envoy; Cordis, Miami Lakes, Florida) or a 5F guiding sheath (Shuttle, Cook, Bloomington, Indiana) was placed in the carotid or vertebral artery.Heparinization was administered to achieve an activated clotting time of Ͼ250 seconds.Various endovascular coil devices were used, usually bare platinum coils.Aneurysms were packed as densely as possible.

Statistical Analysis
Continuous and ordinal data were presented as means (range).Nominal data were presented as counts (percentage).Baseline comparisons of continuous data were between groups by using the Student t test, while nominal data were compared by using a 2 or Fisher exact test when appropriate.Multivariate analysis was performed to identify independent risk factors for the development of complications by using multiple logistic regression adjusting for age, sex, number of aneurysms, largest diameter of aneurysms, and location of aneurysms and whether patients were symptomatic and the type of procedure performed.A P value Ͻ.05 was considered statistically significant.A 95% CI was calculated when applicable.All statistical analyses were performed by using JMP, Version 5.1 software (SAS Institute, Cary, North Carolina).

Patient Population
Three hundred fifty-five patients (76% female; 95% CI, 72%-80%) were identified.These patients underwent 394 elective endovascular treatment sessions during the time period studied.The mean age of patients was 57 years (range, 6 -87 years).Of the 355 patients, 108 were elderly (30%; 95% CI, 26%-35%).Elderly patients were noted to have increased prevalence of hypertension and hyperlipidemia, but this is expected in an elderly population.It was also observed that the elderly population had a significantly larger average aneurysmal size (Table 1).
No difference was noted in the complication rate or demographics of patients who were undergoing treatment for unruptured aneurysms or previously treated ruptured aneurysms (Table 3).Similarly, there was no difference in complication rates between patients on anticoagulation therapy and those not on anticoagulation therapy (Table 4).

Age-Related Risk Factors for Complications
Age older than 65 years was not a significant risk factor for complications overall (P ϭ .18,Table 5).Rates of minor complications were not significantly different between nonelderly and elderly patients (P ϭ .56).However, both major complications overall (7.4 versus 17% for nonelderly and elderly patients, respectively, P ϭ .004)and major complications associated with neurologic deficit (1.8% versus 8.2% for nonelderly and elderly patients, respectively, P ϭ .004)were significantly more prevalent in the elderly compared with nonelderly patients (Table 5).

Discussion
In the current study, we demonstrated that elderly patients undergoing elective endovascular intracranial aneurysm treatment do not have a greater overall complication rate compared with nonelderly patients.However, major complications, particularly major complications associated with neurologic deficits, occurred at a significantly greater rate in the elderly population compared with the nonelderly population, with elderly patients having such complications 4 times as frequently as nonelderly patients.One potential explanation for this observed difference in major complication rates is that the "vascular reserve" of elderly patients is compromised; thus, any type of ischemic insult may lead to symptoms that might be subclinical in younger patients. 17symptomatic diffusion abnormalities are common after coil embolization, occurring in Ͼ50% of patients in many series. 18Furthermore, elderly patients have tortuous vasculature and atherosclerotic disease in the aortic arch and intracranially, making them prone to complications. 19While these explanations cannot be proved in the current series, the fact that other neuroendovascular procedures, including carotid stent placement, appear relatively poorly tolerated in elderly patients lends credence to the concept of diminished vascular reserve. 17,19Although these 2 articles 17,19 on this subject had   different age cutoffs for the elderly (70 and 80, respectively), the idea of diminished vascular reserve can be applied to elderly patients in general, because it is a gradual phenomenon.The findings of elevated risk of major complications indicate that elective coiling in the elderly should be carefully considered, especially given the relative risk of spontaneous hemorrhage and potentially shorter life expectancy than in younger patients.
Relatively few previous studies have examined the complication rate of elderly patients undergoing elective endovascular aneurysm treatment.Most of these previous studies have focused on treatment of elderly patients with ruptured aneurysms. 15,16,20Gonzalez et al 11 reported 97 elderly patients, defined as older than 70 years of age, who had undergone elective aneurysm treatment.In that study, it was determined that being elderly carried no additional risk during coiling.However, the study had no comparison between nonelderly and elderly patients; thus, it could not determine whether coiling had a higher rate of complications within the elderly group.The overall major complication with neurologic deficits rate that we observed was 3.8%, which is comparable with the 3% found by Ross and Dhillon 21 in their study of aneurysms.That study did not examine complications not involving permanent neurologic deficits, and we could not compare the other types of complications to this study or others.
Our mortality rate of 0.5% in the elderly group is lower but comparable with the rate of 1.3% observed by van Roojj and Sluzewski. 22Furthermore, the mortality rate in our elderly group was similar to that of the 0.8% found in the NIS. 23,24lso in the NIS, it was noted that patients aged 65-79 years had a significantly increased mortality rate compared with patients younger than 65 years of age, as shown in the current study. 23his retrospective trial had several limitations.First, it remains possible that with complete follow-up and prospectively defined outcomes, risks might have been higher in both groups than we determined with retrospective data analysis.Second, we defined the elderly as patients older than 65 years of age, while other studies have used different age thresholds.A third limitation was in the observation that the elderly population had an average aneurysmal size larger than that in the nonelderly population, perhaps biasing results because larger aneurysms are more prone to complications such as rupture or lack of compaction. 25Further study may be warranted between elderly and nonelderly cohorts with similar aneurysmal sizes.

Table 3 : Comparison of previously ruptured aneurysms and unruptured aneurysms a
Although the number of coils and size of aneurysm varied between unruptured aneurysms and previously ruptured ones, there was no difference in the complication rate between the 2 groups.
Note:-NS indicates not significant.a