Treatment of Unruptured Intracranial Aneurysms: A Nationwide Assessment of Effectiveness

Methods

Results

A total of 2535 treated unruptured cerebral aneurysm cases, in 429 hospitals, were identified. Seventy-four percent (1881) were surgically treated. Patients identified in the study were a mean of 54 years of age, predominantly female, and predominantly admitted from home (Table 1). There were more men in the endovascular group compared with the neurosurgical group (P < .05). The admission source (P < .0001) differed significantly between the treatment groups. Compared with endovascular cases, neurosurgical cases were more likely to be admitted through the emergency department (ED) (12% versus 7%), and less likely to be admitted from home or as a transfer case (87% versus 93%). There were also statistical treatment variations based on the treating institution’s geographic location (P < .05).

The mean comorbidity scores, reflecting existing conditions, for the neurovascular and endovascular groups were not significantly different (P > .73) for any study outcome. The most frequent comorbid conditions on discharge records were hypertension (39%), chronic pulmonary disease (11%), and arrhythmia (5.4%). Neurosurgical cases were more likely than endovascular cases to have deficiency anemia (3.6% versus 2.0%, P < .05), but this condition was not related to either death or adverse outcome. Conditions associated with adverse outcomes included hypertension, congestive heart failure, peripheral vascular disease, and arrhythmia (P < .05). Only coagulopathy was associated with an in-hospital death (P < .05).

Diagnoses and procedures excluded from the comorbidity index that could potentially indicate a condition or procedure related to the treatment outcomes are displayed in Table 2. Compared with endovascular cases, neurosurgical cases were significantly (P < .05) more likely to have the following procedures or diagnoses: cranial nerve palsy, ventriculostomy, postoperative neurologic complications, endotracheal tube placed, mechanical ventilation, gastrostomy, packed red blood cell transfusion, other surgical complication or postoperative infection, and physical or occupational therapy.

Adverse outcome status was assigned to 11.5% of all treated unruptured aneurysms, including 2.1% procedural mortality at discharge (Table 3). The proportion of adverse outcomes was approximately double for neurosurgical cases compared with the endovascular-treated cases (13.2% versus 6.6%, P < .0001). The in-hospital neurosurgical mortality was more than twice the rate of endovascular mortality (2.5% versus 0.9%, P < .05). The length of stay for neurosurgical cases was significantly longer than for endovascular cases averaging 7.4 versus 4.5 days (P < .0001). Mean hospital charges were $5523 more for neurosurgical treatment than for endovascular treatment (P < .0001). Similar trends are reported for the group when stratified by ED admissions. When ED admissions were excluded from the analysis, the neurosurgical mortality rate decreased from 2.5% to 1.9%. With the exception of in-hospital death, all differences between the 2 types of treatments remained statistically significant when ED admissions were excluded.

Table 4 reports the adjusted ratios and confidence intervals comparing neurosurgical versus endovascular treatments in multivariable models. Power calculations, which indicate the level of confidence that a correct decision was made to reject the null hypothesis, are also reported. Neurosurgical cases had 70% greater odds of an adverse outcome compared with endovascular cases after adjustment for age, sex, Medicaid status, geographic region, year of treatment, comorbidity score, volume quartile, and admission source (OR = 1.7; 95% confidence interval [CI], 1.2, 2.5). After multivariable adjustment, neurosurgical treatment was associated with 2.3 times the odds of death of endovascular treatment (95% CI, 0.97, 5.7), though small numbers resulted in a low statistical power. The geometric mean length of stay was almost twice as long (OR = 1.8; 95% CI, 1.6, 2.0) and hospital charges were 30% higher (OR = 1.3; 95% CI, 1.2, 1.5) for neurosurgical treatments compared with endovascular treatments. Trends were similar for the analyses stratified by ED for all outcomes. Zero deaths in the endovascular group preclude multivariable comparison on this outcome in the emergency admission group.

Discussion

This is the first nationwide study to assess the effectiveness of endovascular and neurosurgical treatment for unruptured intracranial aneurysms at hospital discharge in a geographically diverse sample of community and academic medical centers. First, it has been shown that endovascular therapy was associated with significantly fewer adverse outcomes at discharge compared with neurosurgical treatment for unruptured cerebral aneurysms. Second, endovascular treated cases were less resource-intensive during the treatment hospitalization than neurosurgical cases, having significantly shorter lengths of stay and lower hospital charges. Third, surgical mortality was more than twice as high as endovascular mortality in multivariable analyses.

Both neurosurgical and endovascular treatment of intracranial aneurysms are associated with procedural risks and complications such as disability or death. The International Study of Unruptured Intracranial Aneurysms, a prospective study of 995 surgically treated patients, reported a 1-year neurosurgical mortality rate of 3.2% and a disability rate of 12%.²³ A meta-analysis of 2460 unruptured aneurysm cases in 61 publications between January 1966 and June 1996 reported a neurosurgical mortality rate of 2.6% and morbidity rate of 10.9%.⁶ A more recent study of 3498 unruptured aneurysms treated with neurosurgical clipping from 1996 to 2000 reported in-hospital mortality at 2.1% and death or discharge other than home at 18.3%.²¹ Our findings of a 2.5% mortality rate and a 13.2% adverse outcome rate in patients with a neurosurgically treated unruptured aneurysm are consistent with these published reports.

Comparative studies of neurosurgical versus endovascular treatment outcomes for unruptured aneurysms are limited to 2 retrospective cohorts.^14,24 In 2069 California patients treated from 1990 to 1998, there was significantly less morbidity (9.7% versus 25.4%), mortality (0.5% versus 3.5%), and resource use (7.1 versus 11.7 hospital days; $37,000 versus $63,000 hospital charges, P < .01) for those receiving endovascular coiling versus neurosurgical clipping treatment.²⁴ Likewise, in 2612 patients treated between 1994 and 1997 at 70 US academic medical centers, there were decreased adverse outcomes (10.6% versus 18.5%), procedural mortality (0.4% versus 2.3%), and hospital resource use (4.6 versus 9.6 hospital days; $30,000 versus $43,000 hospital charges) (P < .04).¹⁴ Our results for 2535 cases, treated at 429 hospitals in 18 states, over a 1-year period are comparable with these prior studies (Table 3). Procedural mortality in the current study was <1% for endovascular treatment versus 2.5% for neurosurgical treatment.

Procedures and diagnoses related to postoperative complications give insight into the relative safety of these procedures and potential reasons for the differences observed in discharge outcomes. Neurosurgical cases received more surgical interventions, compared with cases treated with endovascular therapy (Table 2). For neurosurgical cases, the greater hospital resource use and more frequent adverse outcomes may be explained by the increased rates of postoperative complications and rehabilitation services. Examination of the secondary diagnoses associated with mortality also suggests the prominent association of postoperative complications with death. Diagnoses significantly (P < .0001) associated with the 53 total deaths in the study included postoperative neurologic complications (42%), occlusion of cerebral artery (23%), postoperative infections (23%), postoperative respiratory insufficiency (15%), and hydrocephalus (11%). Postoperative stroke was the most common diagnosis on mortality cases, present on 40% (21/53) of records.

ED admission may also indicate an acute case with confounding physiologic variability. From a clinical standpoint, patients admitted urgently tend to be more symptomatic, presenting with headache, pain, or focal neurologic signs. This study confirmed this observation: ED admissions were diagnosed with headache and cranial nerve palsy at triple the rate of non-ED admissions. These symptoms are more frequent with larger aneurysms adjacent to cranial nerves or eloquent brain regions, which may indicate risk for poorer treatment outcomes. Cases admitted through the ED also had triple the death rate (5.5% versus 1.7%) and 1.5 times the adverse outcome rate (16.8% versus 10.9%) of non-ED admissions. The small sample size for this analysis results in limited power for comparisons; thus, conclusions about which treatment has an advantage for ED admissions can be very limited. Our findings suggest that unruptured aneurysm patients presenting in an emergency room are a unique subgroup at higher risk for poor outcomes with either treatment.

Worldwide, it is estimated that more than 220,000 patients with intracranial aneurysms have now been treated with endovascular coiling techniques, at over 2000 medical centers, with approximately 3500–4000 patients currently treated per month, a figure that has steadily increased since 1990.²⁵ This study indicates that patients were treated with surgery (74%) in higher proportions than endovascular therapy (26%) during the time interval of this analysis. Patients admitted through the ED were even more frequently (85%) operated upon during the time of this study. However, with the emergence of new evidence that endovascular therapy may have a better overall outcome for patients with an unruptured cerebral aneurysm, a change of current practice patterns may be warranted.^7,12 A multidisciplinary approach to patient care may improve overall clinical outcome and patients should be completely informed about the option of endovascular coiling as a viable treatment option in all cases.²⁶

Conclusion

This is the first nationwide effectiveness study to have evaluated the treatment of unruptured intracranial aneurysms in a geographically diverse sample of 429 community and academic medical centers in a 1-year time period. The current analysis indicates that endovascular therapy is associated with significantly less morbidity, less mortality, and decreased hospital resource use at discharge, compared with conventional neurosurgical treatment for all unruptured aneurysms.

Efficacy studies, such as randomized clinical trials are a major factor in adopting a particular procedure or therapy; however, this evidence applies only to patients and hospitals with characteristics comparable with those of the trial participants. In contrast, effectiveness research, similar to the study reported here, has high external validity because it directly samples therapy as practiced in the field. Endovascular therapy, as a treatment alternative to surgical clipping, should be offered as a viable therapeutic option for all patients considering treatment of an unruptured cerebral aneurysm.