Factors influencing management of unruptured intracranial aneurysms: an analysis of 424 consecutive patients

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OBJECTIVE

The choice between treating and observing unruptured intracranial aneurysms is often difficult, with little guidance on which variables should influence decision making on a patient-by-patient basis. Here, the authors compared demographic variables, aneurysm-related variables, and comorbidities in patients who received microsurgical or endovascular treatment and those who were conservatively managed to determine which factors push the surgeon toward recommending treatment.

METHODS

A retrospective chart review was conducted of all patients diagnosed with an unruptured intracranial aneurysm at their institution between January 1, 2013, and January 1, 2016. These patients were dichotomized based on whether their aneurysm was treated. Demographic, geographic, socioeconomic, comorbidity, and aneurysm-related information was analyzed to assess which factors were associated with the decision to treat.

RESULTS

A total of 424 patients were identified, 163 who were treated surgically or endovascularly and 261 who were managed conservatively. In a multivariable model, an age < 65 years (OR 2.913, 95% CI 1.298–6.541, p = 0.010), a lower Charlson Comorbidity Index (OR 1.536, 95% CI 1.274–1.855, p < 0.001), a larger aneurysm size (OR 1.176, 95% CI 1.100–1.257, p < 0.001), multiple aneurysms (OR 2.093, 95% CI 1.121–3.907, p = 0.020), a white race (OR 2.288, 95% CI 1.245–4.204, p = 0.008), and living further from the medical center (OR 2.125, 95% CI 1.281–3.522, p = 0.003) were all associated with the decision to treat rather than observe.

CONCLUSIONS

Whereas several factors were expected to be considered in the decision to treat unruptured intracranial aneurysms, including age, Charlson Comorbidity Index, aneurysm size, and multiple aneurysms, other factors such as race and proximity to the medical center were unanticipated. Further studies are needed to identify such biases in patient treatment and improve treatment delineation based on patient-specific aneurysm rupture risk.

ABBREVIATIONS CCI = Charlson Comorbidity Index.

Abstract

OBJECTIVE

The choice between treating and observing unruptured intracranial aneurysms is often difficult, with little guidance on which variables should influence decision making on a patient-by-patient basis. Here, the authors compared demographic variables, aneurysm-related variables, and comorbidities in patients who received microsurgical or endovascular treatment and those who were conservatively managed to determine which factors push the surgeon toward recommending treatment.

METHODS

A retrospective chart review was conducted of all patients diagnosed with an unruptured intracranial aneurysm at their institution between January 1, 2013, and January 1, 2016. These patients were dichotomized based on whether their aneurysm was treated. Demographic, geographic, socioeconomic, comorbidity, and aneurysm-related information was analyzed to assess which factors were associated with the decision to treat.

RESULTS

A total of 424 patients were identified, 163 who were treated surgically or endovascularly and 261 who were managed conservatively. In a multivariable model, an age < 65 years (OR 2.913, 95% CI 1.298–6.541, p = 0.010), a lower Charlson Comorbidity Index (OR 1.536, 95% CI 1.274–1.855, p < 0.001), a larger aneurysm size (OR 1.176, 95% CI 1.100–1.257, p < 0.001), multiple aneurysms (OR 2.093, 95% CI 1.121–3.907, p = 0.020), a white race (OR 2.288, 95% CI 1.245–4.204, p = 0.008), and living further from the medical center (OR 2.125, 95% CI 1.281–3.522, p = 0.003) were all associated with the decision to treat rather than observe.

CONCLUSIONS

Whereas several factors were expected to be considered in the decision to treat unruptured intracranial aneurysms, including age, Charlson Comorbidity Index, aneurysm size, and multiple aneurysms, other factors such as race and proximity to the medical center were unanticipated. Further studies are needed to identify such biases in patient treatment and improve treatment delineation based on patient-specific aneurysm rupture risk.

Unruptured intracranial aneurysms are harbored by approximately 3% of adults.33 Although aneurysm rupture is often devastating, the diverse factors influencing rupture risk combined with the low overall rate of rupture result in significant variation in how aneurysms are treated.9,12,16,19,24,32 The choice between intervening and observing is further complicated by the risk of treatment itself, which remains significant even though it decreases as microsurgical and endovascular techniques improve.13,15,35 Non–disease-specific variables such as patient anxiety6 often play an important role in how aneurysms are managed, leading to situations in which nearly identical lesions may be approached in different ways. Several studies have demonstrated an effect of socioeconomic factors in the decision to treat ruptured and unruptured aneurysms,3,5 although one recent study suggested that sex and race biases associated with treatment groups have decreased over time.20 Most of these studies have relied on large International Classification of Diseases (ICD)–based hospital databases, limiting their ability to examine patient- and aneurysm-level characteristics.

Although significant attention has been paid to determining the natural history of unruptured cerebral aneurysms,11,14,29 less is known about the factors that practicing neurosurgeons distill from the literature to use in making treatment decisions on a patient-by-patient basis. Such information would be useful in evaluating which of the myriad risk factors for rupture most frequently push the surgeon toward recommending treatment. Our objective in the present study was to perform an analysis of demographic variables, aneurysm-related variables, and comorbidities to compare patients with unruptured aneurysms who received microsurgical or endovascular treatment and those who were observed.

Methods

Patient Cohort

After obtaining approval from the institutional review board, we retrospectively queried a prospectively collected University of Utah clinical database to obtain information about patients 18 years and older with a diagnosed unruptured intracranial aneurysm seen between January 1, 2013, and January 1, 2016. Individual chart review was then performed to determine which patients received treatment for their aneurysms and which were managed with observation. Patients were excluded if geographic, demographic, or socioeconomic data were unavailable. Patients were also excluded if they were younger than 18 years old at the time of aneurysm diagnosis and/or treatment or if the initial treatment decision for their aneurysm was made prior to January 1, 2013. All treatment decisions were made by 1 of 5 neurosurgeons (W.T.C., R.H.S., J.D.M., P.T., M.S.P.) on a patient-by-patient basis. All endovascular and microsurgical procedures were performed by these same 5 neurosurgeons.

Data Collection

Demographic, geographic, socioeconomic, comorbidity, and aneurysm-related information were collected on all patients. Specific variables were chosen based on those purportedly associated with a higher risk of rupture in the most recent American Heart Association and American Stroke Association guidelines.31 Demographic data included age (dichotomized by age ≥ or < 65 years), race/ethnicity (dichotomized into white and non-white), sex, marital status, and insurance type (divided into private, Medicaid/self pay, and Medicare). Each patient's ZIP code was collected and used to estimate median household income for each patient based on United States census data (http://www.census.gov/). Travel distance to the University of Utah Medical Center for each patient was also calculated from the patient's ZIP code utilizing Google Maps (http://maps.google.com) and was dichotomized based on the median travel distance (32.2 miles). Comorbidity data included active tobacco use, active alcohol use, and active illicit drug use. Data on family history of intracranial aneurysms, previous aneurysmal subarachnoid hemorrhage, multiple intracranial aneurysms, and other disorders associated with intracranial aneurysm development and/or rupture (polycystic kidney disease, hereditary hemorrhagic telangiectasia, arteriovenous malformations, and so forth) were also collected. For each patient, a Charlson Comorbidity Index (CCI) score was calculated based on published criteria.8

Aneurysm-related data included aneurysm size (in mm), multilobulated or irregular appearance, and aneurysm location. Aneurysm location was divided into 7 categories based on those used in previous publications.12 Information on whether each aneurysm was treated or managed conservatively was obtained. Finally, for those lesions that were treated, the documented reason for this decision was collected.

Statistical Analysis

Continuous variables were analyzed using the Student t-test, and categorical variables were analyzed using chi-square analysis. Univariate analysis was performed to compare patients whose aneurysms were treated and those whose aneurysms were managed with observation. Factors with a p < 0.2 in the univariate analysis were included in a multivariable model. In all analyses, p < 0.05 was considered statistically significant. All statistical analysis was performed using SPSS version 20.0 (IBM Corp.).

Results

The sex (73% vs 67% female, p = 0.196) and marital status (64% vs 59% married, p = 0.325) of the 163 treated and 261 untreated patients were similar (Table 1). Patients who underwent treatment for their unruptured intracranial aneurysms were significantly less likely to be 65 years or older at the time of intervention and/or diagnosis (23% vs 57%, p < 0.001) and were significantly more likely to be white (82% vs 72%, p = 0.021). Patients who were treated were also significantly more likely to have private insurance instead of Medicare, Medicaid, or self pay (55% vs 38%, p < 0.001). Median household income based on ZIP code was not significantly different between the 2 groups, although treated patients were significantly more likely than those managed conservatively to have a longer travel distance to the hospital (61% vs 43%, p < 0.001).

TABLE 1.

Univariate analysis of treated versus untreated unruptured aneurysms

VariableNo. (%)p Value*
UntreatedTreated
No. of patients261163
Female patients175 (67)119 (73)0.196
Age ≥ 65 yrs149 (57)38 (23)<0.001
Married154 (59)104 (64)0.325
Race/ethnicity
  White189 (72)134 (82)0.021
  Non-white72 (28)29 (18)
Payer type
  Private100 (38)89 (55)<0.001
  Medicaid/self pay28 (11)26 (16)
  Medicare133 (51)48 (29)
Mean CCI ± SD3.28 ± 1.971.87 ± 1.53<0.001
Hypertension147 (56)80 (49)0.146
Previous aneurysmal SAH1 (0.4)2 (1)0.313
Multiple aneurysms33 (13)47 (29)<0.001
Multilobulated/irregular aneurysm41 (15.7)54 (33.1)<0.001
Family history of aneurysms16 (6)22 (13)0.010
Other predisposing disorder14 (5)8 (5)0.837
Tobacco use40 (15)43 (26)0.005
Alcohol use63 (24)48 (29)0.226
Illicit drug use8 (3)3 (2)0.440
Median household income ± SD$60,976.37 ± $18,322.47$60,794.95 ± $15,373.160.916
Shorter travel distance149 (57)63 (39)<0.001
Aneurysm location
  Internal carotid artery72 (28)54 (33)0.184
  ACoA/ACA62 (24)31 (19)
  MCA57 (22)29 (18)
  PCoA19 (7)10 (6)
  Basilar tip11 (4)8 (5)
  Other posterior circulation13 (5)18 (11)
  Cavernous carotid artery27 (10)13 (8)
Aneurysm size (mm) ± SD5.14 ± 3.818.32 ± 6.75<0.001

ACA = anterior cerebral artery; ACoA = anterior communicating artery; MCA = middle cerebral artery; PCoA = posterior communicating artery; SAH = subarachnoid hemorrhage.

A p value < 0.05 was considered significant. Boldface type indicates significance.

There were no significant differences between the treated and untreated groups in rates of hypertension (49% vs 56%, p = 0.146), previous aneurysmal subarachnoid hemorrhage (1% vs 0.4%, p = 0.313), or other predisposing disorders, including abdominal aortic aneurysm and polycystic kidney disease (5% vs 5%, p = 0.837). Patients who underwent treatment had significantly lower CCI scores (1.87 ± 1.53 vs 3.28 ± 1.97, p < 0.001), were more likely to have multiple intracranial aneurysms (29% vs 13%, p < 0.001), and more commonly demonstrated a family history of aneurysms (13% vs 6%, p = 0.010). Although treated patients had a higher incidence of active tobacco use (26% vs 15%, p = 0.005), rates of alcohol and illicit drug use were similar between the 2 groups. Aneurysms in the treated cohort were significantly larger than those in the untreated cohort (8.32 ± 6.75 vs 5.14 ± 3.81 mm, p < 0.001) and were more likely to have a multilobulated or irregular appearance (33.1% vs 15.7%, p < 0.001), but the locations of aneurysms in the 2 groups were similar.

In our multivariable model (Table 2), multiple aneurysms (p = 0.020), a larger aneurysm (p < 0.001), and a younger age (p = 0.010) were associated with a higher incidence of aneurysm treatment rather than observation, as were a white race (p = 0.008) and living further from our medical center (p = 0.003). In contrast, patients with a higher CCI were more likely to be managed conservatively (p < 0.001).

TABLE 2.

Multivariable analysis of treated versus untreated unruptured aneurysms

VariableOR (95% CI)p Value*
Aneurysm location0.255
  Internal carotid artery (ref)NANA
  ACoA/ACA0.918 (0.460–1.831)0.808
  MCA1.094 (0.535–2.235)0.805
  PCoA1.054 (0.370–2.996)0.922
  Basilar tip0.988 (0.277–3.519)0.985
  Other posterior circulation2.484 (0.917–6.726)0.073
  Cavernous carotid artery0.434 (0.163–1.155)0.095
Payer0.967
  Private (ref)NANA
  Medicaid/self pay1.096 (0.508–2.366)0.816
  Medicare1.062 (0.493–2.290)0.878
Hypertension1.447 (0.846–2.473)0.177
Family history of aneurysm1.132 (0.487–2.632)0.774
Multiple aneurysms2.093 (1.121–3.907)0.020
Multilobulated/irregular aneurysm1.612 (0.907–2.864)0.104
Tobacco use1.072 (0.578–1.989)0.825
Male sex0.639 (0.367–1.111)0.112
White race2.288 (1.245–4.204)0.008
Longer travel distance2.125 (1.281–3.522)0.003
Larger aneurysm size1.176 (1.100–1.257)<0.001
Lower CCI1.536 (1.274–1.855)<0.001
Younger age2.913 (1.298–6.541)0.010

NA = not applicable.

A p value < 0.05 was considered significant. Boldface type indicates significance.

Discussion

The choice between treating or observing unruptured intracranial aneurysms remains a difficult one in many cases, requiring the distillation of a vast amount of literature regarding the risk factors of each lesion and each specific patient. Significant efforts have been made to develop tools to help guide decision making, but a validated instrument with broad acceptance remains elusive.10 We analyzed a cohort of 424 consecutive patients managed over the course of a 3-year period to determine what factors were associated with the decision to treat or to observe. In our multivariable analysis, we found that multiple aneurysms, a larger aneurysm size, a lower CCI, and a younger age were associated with a decision to pursue treatment. These variables are fairly unsurprising as they correlate well with the most recent recommendations regarding factors that should be considered when deciding how to manage unruptured intracranial aneurysms.31

Although multilobulated or irregular aneurysms were significantly more likely to be treated than less dysplastic lesions, this variable was not significant in our multivariable analysis. This may be due to the significant association between lesion size and irregular appearance in our cohort, with irregular lesions being significantly larger on average than more smooth-walled aneurysms (7.73 ± 4.56 vs 5.97 ± 5.52 mm, p = 0.005). Concurrent pathology, previous aneurysmal subarachnoid hemorrhage, and family history of aneurysm were also not significantly associated with the decision to treat, despite being associated with higher rates of rupture.18,27 This finding is likely due to the small number of patients demonstrating these risk factors in our patient cohort. Similarly, we found no significant association between aneurysm location and the decision to treat, despite evidence that lesions in locations such as the anterior communicating artery22 and the posterior circulation28 are more prone to rupture. This finding may be due to the relatively small number of aneurysms falling into each location category, and such limitations in power mark a significant limitation in our study.

Somewhat surprisingly, a non-white race and greater proximity to our medical center were both associated with a higher likelihood of conservative unruptured aneurysm management. The reasons for this disparity are probably multifactorial, and there is scant literature examining the topic of racial, ethnic, and geographic disparities in aneurysm management. With regard to racial differences, one important factor is likely the continued income inequality that exists along racial and ethnic lines in the United States.23 In our population, the calculated median household income for non-white patients was more than $7,000 less than that for white patients ($55,561.37 vs $62,578.06, p < 0.001). Such differences can have a significant effect on access to and utilization of health care resources.

Multiple studies also suggest that minorities have had poor access to interventional procedures such as carotid endarterectomy17 and coronary angiography,1 as well as disproportionally worse outcomes for diseases such as abdominal aortic aneurysm,25 cerebrovascular diseases,34 and traumatic brain injury.30 Moreover, studies in the oncological literature suggest that complex decisions such as whether to have surgery are approached differently by different racial or ethnic groups and that such differences may influence the willingness of patients to undergo treatment.21 One recent study suggested that sex and racial subgroup differences for aneurysm treatment decreased to nonsignificance between 1998 and 2007,20 but that study, a large ICD-based database study, was limited by the potential for limited ascertainment of aneurysm rupture and treatment status (Table 3). An awareness of these differences and further inquiry into the topic would likely improve the ability of practitioners to provide appropriate counseling to an increasingly diverse population.

TABLE 3.

Review of literature addressing socioeconomic disparities in decisions to treat cerebral aneurysms

Authors & YearSample SizeStudy PopulationFindings
Lin et al., 201220,134 RIAs; 14,765 UIAs; 100% treatedNIS, 1998–2007Increased rate of UIAs treated over epoch; increased ratio of coiling/clipping of both RIAs and UIAs; whites (OR 1.30) and men (OR 1.26) more likely to undergo coiling; sex and racial subgroup differences in treatment nonsignificant by 2007
Bekelis et al., 201457,418 UIAs; 18,231 treatedNIS, 2000–2010Male (OR 0.67), Asian (OR 0.88), Hispanic (OR 0.76), African American (OR 0.57), and patients w/o insurance (OR 0.76) less likely to undergo treatment; patients w/lower CCI (OR 3.03), Medicaid coverage (OR 1.12), private insurance coverage (OR 1.92), and lower income (OR 1.22) more likely to undergo treatment; regional variability in treatment rates seen
Brinjikji et al., 201273,224 UIAs; 89,168 RIAs; 100% treatedNIS, 2001–2009Women and whites more likely to undergo treatment for UIA than RIA; self-payers more likely to undergo treatment for RIA than UIA

NIS = Nationwide Inpatient Sample database; RIA = ruptured intracranial aneurysm; UIA = unruptured intracranial aneurysm.

Even less information is available regarding the influence of travel distance on decisions related to the management of intracranial aneurysms. Perhaps patients who live closer to a tertiary care center are more likely to choose conservative observation of their aneurysm because the routine surveillance imaging required in concert with conservative management is easier to access when the patient does not live prohibitively far away. Patients may also have increased anxiety regarding their ability to access life-saving care in the event of aneurysm rupture if they live in a remote area with limited medical services. Proximity to tertiary care medical centers has been an important factor on follow-up for chronic care as well as access to specialists.2,7

Despite the strong internal validity of our study in comparison with other large database studies, there are several limitations. The first is its retrospective nature, which increases its vulnerability to confounding. Our study is also limited to a single institution, and the decision-making strategies used by the practitioners likely differ somewhat from those used at other centers. Any study of treatment decisions, especially in complex conditions in which physician and patient interpretation of available information plays a major role in the choice of management, is vulnerable to bias resulting from the subset of the population studied. While a prospective multicenter study would be the ideal instrument with which to analyze the variables that drive the decision to treat or observe unruptured intracranial aneurysms, history has demonstrated the significant challenges associated with conducting prospective trials in this field.26 It would likely be especially difficult to reconcile differences between centers with an algorithmic approach to unruptured cerebral aneurysm management and those in which decisions are more routinely made on a patient-by-patient basis. While it would be unreasonable to assume that our group of physicians is representative of all practitioners treating unruptured intracranial aneurysms, the fact that the majority of variables that significantly impacted management decisions are the same as those outlined in the most recent guidelines31 suggests that our practices do not deviate drastically from the accepted norm.

One important factor in the decision to treat or observe intracranial aneurysms was not assessed in our cohort—namely, aneurysm growth on serial imaging. Because we limited our analysis to a 3-year period and a proportion of our patients have not been followed up long enough for serial imaging to be performed, such an analysis was not possible. We believe it likely, however, that significant growth over time is associated with the decision to treat versus the choice to continue conservative management—and indeed aneurysm growth was cited as the primary impetus for treatment in nearly 10% of our cohort (Table 4).

TABLE 4.

Reasons for aneurysm treatment in the present study

Treatment ReasonNo. of Patients (%)
Aneurysm growth on serial imaging15 (9.2)
Aneurysm morphology12 (7.4)
Aneurysm size29 (17.8)
Patient anxiety28 (17.2)
Family history11 (6.7)
Comorbidities*9 (5.5)
Multiple aneurysms3 (1.8)
Neurological symptoms34 (20.8)
Young patient age22 (13.5)

Medical conditions believed to place the patient at high risk of aneurysm rupture (for example, polycystic kidney disease, previous subarachnoid hemorrhage).

In any medical or surgical treatment, the agency of the patient is vital to the decision-making process. The role of patient preference—specifically anxiety related to an unruptured intracranial aneurysm—is an acknowledged contributor to the choice of whether to treat or observe these lesions.9 This was very much true in our cohort, in which patient anxiety was the third most common reason cited for treatment of unruptured aneurysms over observation. Lack of quantification of such patient measures, especially in patients who elected not to be treated, represents another weakness of our study and the literature on unruptured intracranial aneurysm management as a whole.4 Future investigations into the patient decision-making process when faced with an unruptured aneurysm could contribute significantly to our ability to counsel this population.

While our study does not elucidate any new findings that can guide neurosurgeons in the difficult decision of whether to treat or observe unruptured intracranial aneurysms, it does offer an assessment of what known variables are most likely to influence this choice in this patient population. It also suggests that beyond individual medical and aneurysm characteristics, factors as broad as racial background and geographic access to neurosurgical care can have significant effects on how these patients are managed. Knowledge of these possible biases may help neurosurgeons to better advise these patients and their families.

Conclusions

Larger aneurysm size, younger age, lower CCI, and multiple aneurysms are associated with the decision to treat rather than observe unruptured intracranial aneurysms, as are a white race and a longer travel distance to the treatment center. Further inquiry, preferably at multiple centers with diverse patient populations, is needed to better elucidate what variables significantly impact treatment decisions in the management of unruptured intracranial aneurysms.

Acknowledgments

We thank Kristin Kraus, MSc, for editorial assistance.

Disclosures

Dr. Taussky is a consultant for Covidien.

Author Contributions

Conception and design: Park, Guan. Acquisition of data: Guan. Analysis and interpretation of data: Guan, Karsy. Drafting the article: Park, Guan. Critically revising the article: Park, Karsy, Couldwell, Schmidt, Taussky, MacDonald. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Park. Administrative/technical/material support: Couldwell, Schmidt, Taussky, MacDonald. Study supervision: Park.

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Article Information

Correspondence Min S. Park, Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, 175 N Medical Dr. East, Salt Lake City, UT 84132. email: neuropub@hsc.utah.edu.

INCLUDE WHEN CITING Published online October 7, 2016; DOI: 10.3171/2016.7.JNS16975.

Disclosures Dr. Taussky is a consultant for Covidien.

© AANS, except where prohibited by US copyright law.

Headings

References

1

Alter DANaylor CDAustin PTu JV: Effects of socioeconomic status on access to invasive cardiac procedures and on mortality after acute myocardial infarction. N Engl J Med 341:135913671999

2

Arcury TAGesler WMPreisser JSSherman JSpencer JPerin J: The effects of geography and spatial behavior on health care utilization among the residents of a rural region. Health Serv Res 40:1351552005

3

Bekelis KMissios SLabropoulos N: Regional and socioeconomic disparities in the treatment of unruptured cerebral aneurysms in the USA: 2000–2010. J Neurointerv Surg 6:5565602014

4

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