Cost-effectiveness analysis in patients with an unruptured cerebral aneurysm treated with observation or surgery

Charlotte Dandurand Faculty of Medicine, Divisions of Neurosurgery and
T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts

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Lily Zhou T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
Neurology, University of British Columbia, Vancouver, Canada; and

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Swetha Prakash Faculty of Medicine, Divisions of Neurosurgery and

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Gary Redekop Faculty of Medicine, Divisions of Neurosurgery and

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Peter Gooderham Faculty of Medicine, Divisions of Neurosurgery and

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Charles S. Haw Faculty of Medicine, Divisions of Neurosurgery and

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OBJECTIVE

The main goal of preventive treatment of unruptured intracranial aneurysms (UIAs) is to avoid the morbidity and mortality associated with aneurysmal subarachnoid hemorrhage. A comparison between the conservative approach and the surgical approach combining endovascular treatment and microsurgical clipping is currently lacking. This study aimed to conduct an updated evaluation of cost-effectiveness comparing the two approaches in patients with UIA.

METHODS

A decision tree with a Markov model was developed. Quality-adjusted life-years (QALYs) associated with living with UIA before and after treatment were prospectively collected from a cohort of patients with UIA at a tertiary center. Other inputs were obtained from published literature. Using Monte Carlo simulation for patients aged 55, 65, and 75 years, the authors modeled the conservative management in comparison with preventive treatment. Different proportions of endovascular and microsurgical treatment were modeled to reflect existing practice variations between treatment centers. Outcomes were assessed in terms of QALYs. Sensitivity analyses to assess the model’s robustness and completed threshold analyses to examine the influence of input parameters were performed.

RESULTS

Preventive treatment of UIAs consistently led to higher utility. Models using a higher proportion of endovascular therapy were more cost-effective. Models with older cohorts were less cost-effective than those with younger cohorts. Treatment was cost-effective (willingness to pay < 100,000 USD/QALY) if the annual rupture risk exceeded a threshold between 0.8% and 1.9% in various models based on the proportion of endovascular treatment and cohort age. A higher proportion of endovascular treatments and younger age lowered this threshold, making the treatment of aneurysms with a lower risk of rupture more cost-effective.

CONCLUSIONS

Preventive treatment of aneurysms led to higher utility compared with conservative management. Models with a higher proportion of endovascular treatment and younger patient age were most cost-effective.

ABBREVIATIONS

aSAH = aneurysmal subarachnoid hemorrhage ; ICER = incremental cost-effectiveness ratio ; ISAT = International Subarachnoid Aneurysm Trial ; MRA = magnetic resonance angiography ; mRS = modified Rankin Scale ; PSA = probabilistic sensitivity analysis ; QALY = quality-adjusted life-year ; UIA = unruptured intracranial aneurysm .

OBJECTIVE

The main goal of preventive treatment of unruptured intracranial aneurysms (UIAs) is to avoid the morbidity and mortality associated with aneurysmal subarachnoid hemorrhage. A comparison between the conservative approach and the surgical approach combining endovascular treatment and microsurgical clipping is currently lacking. This study aimed to conduct an updated evaluation of cost-effectiveness comparing the two approaches in patients with UIA.

METHODS

A decision tree with a Markov model was developed. Quality-adjusted life-years (QALYs) associated with living with UIA before and after treatment were prospectively collected from a cohort of patients with UIA at a tertiary center. Other inputs were obtained from published literature. Using Monte Carlo simulation for patients aged 55, 65, and 75 years, the authors modeled the conservative management in comparison with preventive treatment. Different proportions of endovascular and microsurgical treatment were modeled to reflect existing practice variations between treatment centers. Outcomes were assessed in terms of QALYs. Sensitivity analyses to assess the model’s robustness and completed threshold analyses to examine the influence of input parameters were performed.

RESULTS

Preventive treatment of UIAs consistently led to higher utility. Models using a higher proportion of endovascular therapy were more cost-effective. Models with older cohorts were less cost-effective than those with younger cohorts. Treatment was cost-effective (willingness to pay < 100,000 USD/QALY) if the annual rupture risk exceeded a threshold between 0.8% and 1.9% in various models based on the proportion of endovascular treatment and cohort age. A higher proportion of endovascular treatments and younger age lowered this threshold, making the treatment of aneurysms with a lower risk of rupture more cost-effective.

CONCLUSIONS

Preventive treatment of aneurysms led to higher utility compared with conservative management. Models with a higher proportion of endovascular treatment and younger patient age were most cost-effective.

Intracranial aneurysms have been reported to be found in 3% of the population.1 The incidental finding of an unruptured intracranial aneurysm (UIA) has become more common with increased use of brain imaging.2 Rupture causing aneurysmal subarachnoid hemorrhage (aSAH) is the most feared complication.2 The main goal of preventive treatment of a UIA is to avoid the morbidity and mortality associated with aSAH.2,3

Malhotra et al. found that preventive treatment with coil placement or periodic indefinite imaging was not cost-effective.5 Recently, Silva et al. identified the need to weigh microsurgical clipping and endovascular treatment against conservative managment.6 A comparison between the conservative approach and surgical approach combining endovascular and microsurgical clipping is currently lacking. Despite growing indications for endovascular therapy, not all UIAs are amenable to this technique and microsurgical clipping remains an essential tool in the care of patients diagnosed with a UIA.7 The ideal proportion of patients to be treated with endovascular therapy and microsurgical clipping has not yet been determined, and there is significant practice variation between cerebrovascular surgeons and hospitals.

The aim of this study was to conduct an updated evaluation of cost-effectiveness comparing the conservative approach with a surgical approach (microsurgical clipping and endovascular treatment) in patients with UIA. We aimed to assess the impact that different proportions of microsurgical clipping and endovascular therapy will have on cost-effectiveness estimates. Additionally, prospectively collected index values of patients with unruptured aneurysms have not been used in previous studies.

Methods

Model Structure

A decision tree with a Markov model was developed to estimate the expected lifetime costs and quality-adjusted life-years (QALYs) after conservative and surgical management (Supplementary Fig. 1). The model simulates cohorts of patients with UIA that were randomly allocated to treatment with microsurgical or endovascular treatment versus conservative management. We modeled different proportions of combinations of the two treatment modalities (endovascular proportion 60%, 70%, and 80%) to reflect existing practice variations at different North American centers. Half-cycle corrections were applied for all analysis. A discount rate of 3% was applied to both costs and benefits per standard of practice in cost-effectiveness analysis in the United States. All analysis was done using Amua version 0.2.7 (Zach Ward). Using Monte Carlo simulation modeling, 10,000 patients in three types of cohorts (ages 55, 65, and 75 years) were modeled. Each cohort was followed until all patients died of competing risks (with age- and disability-adjusted risks for each year), aneurysm treatment complications, or a complication of subarachnoid hemorrhage.

Model Estimates

QALYs associated with living with UIA before and after treatment were prospectively collected from a cohort of patients with UIA at a tertiary center. Other clinical parameters were derived from recently published large cohort studies or meta-analyses specific to patients (Table 1). Mild disability corresponded to a modified Rankin Scale (mRS) score of 1 or 2, and major disability was considered as an mRS score of 3–5. Differential annual rates of mortality due to reasons not related to the aneurysm were assigned using the 2016 United States Life Tables.8 Major disability (mRS scores 3–5) was estimated to correspond to a 32% excess in mortality at 30 years.5,9

TABLE 1.

Parameters: probabilities, utilities, and costs

VariableEstimateDistributionReference
Overall annual risk of rupture1.4%β (117,8265)Pooled prospective cohort studies29
Prehospital aSAH case fatality rate12.4%β (475,3357)Meta-analysis30
Untreated aSAH case fatality rate (1 yr)64.7%β (330,180)Large cohort31
Well after treated aSAH (mRS 0)45.2%Dir (90,23,36,50)Prospective cohort11
Mild morbidity after treated SAH (mRS 1 or 2)11.6%Dir (90,23,36,50)Prospective cohort11
Severe morbidity after treated SAH (mRS 3–5)18.1%Dir (90,23,36,50)Prospective cohort11
Death after treated aSAH (mRS 6)25.1%Dir (90,23,36,50)Prospective cohort11
Treatment-related morbidity
 Mild complications after ET3.31%Dir (68041,1185,2377,215)Meta-analysis4,12
 Moderate to severe complications after ET1.65%Dir (68041,1185,2377,215)Meta-analysis4,12
 Death after ET0.30%Dir (68041,1185,2377,215)Meta-analysis4
 Mild complications after MT1.875%Dir (31697,1444,1444,35)Meta-analysis4,12
 Moderate to severe complications after MT1.875%Dir (31697,1444,1444,35)Meta-analysis4,12
 Death after MT0.10%Dir (31697,1444,1444,35)Meta-analysis4
 Annual risk of aSAH after ET0.2%β (3,1392)Meta-analysis32
 Annual risk of aSAH after MT0.05%β (2,4000)Expert authors estimate
 Annual re-treatment rate after ET1.12%β (67,5912)Large cohort13
Cost (2018 USD)
 MR angiography$991.64CPT code17
 CT angiogram$743.73CPT code17
 Cost per year living w/ mild disability$1,341Cost study12
 Cost per year living w/ moderate to severe disability$32,784Cost study5,15
 Mean hospital charges for MT of aneurysm$100,375Cost study6
 Mean hospital charges for ET of aneurysm$93,874Cost study6
 Mean hospital charges for SAH$32,904Cost study5,16

CPT = Current Procedural Terminology; Dir = Dirichlet distribution; ET = endovascular treatment; MT = microsurgical treatment.

Conservative Management

In this group, the risk of aSAH persists lifelong, and only patients who experienced aSAH subsequently underwent treatment for a ruptured intracranial aneurysm. Following aSAH, patients who survived until presentation to the hospital were modeled to undergo treatment with either endovascular therapy or microsurgical clipping at the same proportion of endovascular-to-microsurgical treatment as in the preventive treatment of UIA for the model (endovascular proportion 60%, 70%, or 80%). Patients with recurrent aSAH after treatment who had no neurological deficit or minor deficits were assigned to be treated with the same modality for subsequent treatments based on the study center experience.

We assumed that one-third of the patients with moderate to severe disability from prior aSAH would have an mRS score of 3. These patients would be treated at the time of a subsequent recurrent hemorrhage with the same treatment modality as used previously. We assumed that a patient who has a significant decline in baseline functional status (mRS score 4 or 5) due to treatment-related complications or prior aSAH would not undergo aneurysm occlusion treatment or imaging monitoring for a subsequent aSAH.

For a more conservative estimation of cost-effectiveness for treatment, patients with unruptured aneurysms undergoing conservative management, who do not subsequently require intervention for aneurysmal rupture, were modeled as having no maintenance cost.

Preventive Aneurysm Treatment

Undergoing preventive treatment of a UIA carries immediate risk of death and postoperative complications while reducing the risk of aSAH. Surgical clipping significantly reduces the risk of aSAH with high complete occlusion rates. Endovascular therapy is associated with lower complete occlusion rates and higher rates of recanalization and re-treatment. Reported rates of re-treatment or hemorrhage after surgical clipping are scarce in the literature due to the lack of postoperative imaging or long-term follow-up.10 For this study, with the consensus of expert authors, the risk of aSAH after microsurgical clipping was modeled to be one-quarter of the risk of aSAH after endovascular treatment. Clipping was assumed to not require re-treatment in the absence of aneurysm rupture.10 We modeled risk of aSAH after endovascular treatment at 0.2%.10

Patients with a significant decline in baseline functional status (assumed to be two-thirds of patients with major disability) did not undergo postoperative follow-up imaging. Other patients underwent magnetic resonance angiography (MRA) annually for the first 2 years after treatment and then every 5 years. Those treated with microsurgical clipping underwent CT angiography once at 5 years after treatment. We assumed no losses to follow-up.

Aneurysm Rupture Risk and aSAH Outcomes

The overall annual risk of UIA rupture leading to aSAH was modeled at 1.4%.7 To study the effect of variation in rupture risk in patients with growing, larger, and de novo aneurysms and those harboring multiple aneurysms, we performed a threshold analysis and varied rupture risk to examine the effect on cost-effectiveness. Case fatality rate of aSAH was modeled at 35%.4,11 Of the patients who survived, 60.5% were classified as mRS score 0, 15.4% as mRS score 1 or 2, and 24.1% as mRS scores 3–5.12 We modeled this using Dirichlet distributions. It was assumed that clinical consequences of aSAH were the same between the first and subsequent ruptures and the same for those treated using endovascular versus microsurgical treatments.

Treatment-Related Morbidity and Mortality, and aSAH After Treatment

The postoperative complication rate is 4.96% for endovascular treatment4 based on data from a recent meta-analysis. There are no satisfactory pooled estimates of severity of these complications. We modeled that one-third of patients with treatment-related complications would be moderately to severely disabled (1.65%) and two-thirds would have mild disability (3.31%),13 which is similar to a previous study looking at cost-effectiveness of unruptured aneurysm treatment. The overall case fatality rate was modeled at 0.30%.4 It was assumed that treatment-related complications were the same between the first and subsequent treatments for those requiring re-treatment after receiving initial endovascular treatment. The re-treatment rate after endovascular therapy due to recanalization on surveillance imaging was estimated to be 1.12% per year, adjusted from reported 10-year re-treatment rates.14

The postoperative complication rate for clipping has been reported to be 3.75%.4 Half of the patients with complications were modeled as having mild disability (1.875%) and half as having moderate to severe disability (1.875%).13 The overall case fatality was modeled at 0.1%4 using beta distributions.

Within our models, aneurysms that received a certain treatment modality initially would not cross over to the other treatment modality for subsequent treatments based on the study center experience. Eight health states were defined in patients treated using the conservative strategy and separately for patients who underwent surgical management (Table 2).

TABLE 2.

Health states

Health States (surgical group)Health States (conservative group)Mean QALYMaintenance Cost
Well (mRS 0) w/ untreated aneurysmMean 0.854 (triangular distribution 0.240–1)0
Well (mRS 0) after ET of ruptured or unruptured aneurysmWell (mRS 0) after ETMean 0.872 (triangular distribution 0.132–1)Cost of MRA ($1892) at yrs 1 & 2 postprocedure & every 5 yrs subsequently
Well (mRS 0) after MT of ruptured or unruptured aneurysmWell (mRS 0) after MTMean 0.885 (triangular distribution 0.389–1)Cost of CTA ($744) at yr 5 postprocedure
Minor disability (mRS 1 or 2) after ET of ruptured or unruptured aneurysmMinor disability (mRS 1 or 2) after ETMean 0.72 (triangular distribution 0.65–0.80)Cost associated w/ disability ($1259) & cost of MRA ($1892) at yrs 1 & 2 postprocedure & every 5 yrs subsequently
Minor disability (mRS 1 of 2) after MT of ruptured or unruptured aneurysmMinor disability (mRS 1 or 2) after MTMean 0.72 (triangular distribution 0.65–0.80)Cost associated w/ disability ($1259) & cost of CTA ($744) at yr 5 postprocedure
Major disability (mRS 3–5) after ET of ruptured or unruptured aneurysmMajor disability (mRS 3–5) after ETMean 0.41 (triangular distribution 0.25–0.65)Cost associated w/ disability ($30,813) & cost of MRA ($1892) at yrs 1 & 2 postprocedure & every 5 yrs subsequently for 1/3 of patients
Major disability (mRS 3–5) after MT of ruptured or unruptured aneurysmMajor disability (mRS 3–5) after MTMean 0.41 (triangular distribution 0.25–0.65)Cost associated w/ disability ($30,813) & cost of CTA ($744) at yr 5 postop for 1/3 of patients
Death after ETDeath00
Death after MT

Costs

All costs were inflated to 2018-converted USD amounts using healthcare inflation. The cost of living with a mild and severe disability and hospital charges were extracted from the literature.5,6,13,15,16 Cost for monitoring imaging was derived from Current Procedural Terminology codes.17

Each previously described health state was associated with an annual maintenance cost based on disability derived from the literature (Table 2) separate from the cost of initial treatment, management of subarachnoid hemorrhage, and associated re-treatments.

Utilities

Benefits were measured in QALYs derived from prospectively collected data from the study center and derived from the literature.18 Briefly, EQ-5D-5L value sets were prospectively collected in patients diagnosed with a UIA at the time of consultation and at 1 year after approval from the clinical research ethics board at the University of British Columbia was received. This cohort included patients who were managed conservatively as well as patients who underwent microsurgical clipping and endovascular occlusion. There were no treatment complications resulting in permanent disability impacting the mRS score. The index value was then calculated from the scores obtained.

Aggregate baseline data for the entire cohort were used for QALYs associated with living with an unruptured aneurysm. Because significant differences in baseline health utilities were found in groups that underwent conservative versus surgical management, posttreatment utilities were calculated by adjusting baseline aggregate QALYs with changes to the QALYs within the treated group pre- and posttreatment. As no complications occurred after UIA treatment within our cohort, mean utilities were extracted from the literature for minor disability (mRS score 1 or 2) and severe disability (mRS scores 3–5).18 Functional decline was considered equivalent if related to treatment complications or aSAH.

Cost-Effectiveness and Sensitivity Analysis

Treatments were considered cost-effective at an incremental cost-effectiveness ratio (ICER) of 100,000 USD or less per QALY (willingness to pay).19 To simulate uncertainty around estimated risk inputs, distributions were assigned where possible. Beta or Dirichlet distributions bounded by 0 and 1 were used for inputs related to probability. Triangular distributions were used for QALY estimates. A probabilistic sensitivity analysis (PSA) using 1000 iterations of Monte Carlo simulation with 10,000 patients was then used where input values could be selected at random from these distributions for each simulation.

The impact of annual risk of rupture of UIA and patient age on cost and utility were examined in a 1-way sensitivity analysis. For decisions on patient subgroups, threshold analysis was done to model effects of the differing aSAH risks associated with untreated UIA and the different patient age at the time of a treatment decision.

Results

Base-Case Calculation

In the base-case scenario, surgical management led to higher utility at all 3 endovascular/microsurgical proportion scenarios (endovascular 60%, 70%, and 80%). Increasingly higher ICERs were obtained when a greater proportion of patients underwent surgical clipping when age was kept constant. Increasingly higher ICERs were obtained for older patients (Table 3).

TABLE 3.

Probabilistic sensitivity analysis for 9 cohorts

Proportion of ET/MT in Treatment ArmAge of Cohort (yrs)
556575
ConservativeTreatmentConservativeTreatmentConservativeTreatment
60%/40%
 Cost (USD)601,783,376 ± 59,147,7981,546,941,918 ± 39,436,194401,649,289 ± 39,515,9871,382,836,874 ± 26,921,008232,332,717 ± 22,103,8101,235,431,543 ± 16,173,675
 QALY177,913 ± 36,769196,805 ± 25,893129,175 ± 27,575140,982 ± 18,53583,902 ± 18,45989,952 ± 11,846
 Average ICER50,03183,105165,807
 % ICER <100,000 USD56.0% (95% CI 52.9–59.1%)49.3% (95% CI 46.2–52.5%)40.3% (95% CI 37.6–43.4)
70%/30%
 Cost (USD)603,119,505 ± 58,863,4431,552,196,614 ± 46,558,942403,115,631 ± 39,791,4761,385,274,081 ± 30,936,117232,172,794 ± 21,981,2541,234,999,595 ± 18,676,706
 QALY178,177 ± 36,809199,602 ± 24,849129,353 ± 27,614143,192 ± 17,82283,933 ± 18,45591,455 ± 11,397
 Average ICER44,29970,969133,321
 % ICER <100,000 USD58.8% (95% 55.7–61.9%)51.2% (95% 48.1–54.3%)41.4% (95% CI 38.3–44.5)
80%/20%
 Cost (USD)606,605,898 ± 59,924,0501,589,701,842 ± 51,773,593403,036,222 ± 38,992,9041,410,243,457 ± 35,172,773232,189,398 ± 22,374,4481,244,433,010 ± 21,099,005
 QALY178,339 ± 36,811202,241 ± 24,888129,480 ± 27,607145,048 ± 17,85884,005 ± 18,46592,671 ± 11,416
 Average ICER41,13064,698116,795
 % ICER <100,000 USD60.9% (95% 57.8–63.9)54.1% (95% 51.0–57.2)42.8% (95% CI 39.7–45.9)

Data are presented as the mean ± standard deviation for 1000 simulations of a 10,000-patient cohort.

Probabilistic Sensitivity Analysis

PSA was used to simulate 1000 cohorts of 10,000 patients at each endovascular–to–microsurgical treatment proportion compared with conservative management (Fig. 1). For patients aged 55 years, surgical management resulted in an ICER less than 100,000 USD 56.0% of the time when an endovascular modality was used at proportion 60% (95% CI 52.9%–59.1%), 58.8% of the time when endovascular modality was used at proportion 70% (95% CI 55.7%–61.9%), and 60.9% of the time when endovascular modality was used at proportion 80% (95% CI 57.8%–63.9). For patients aged 65 years, the ICERs were higher. For patients aged 75 years, ICERs were above willingness to pay 100,000 USD.

FIG. 1.
FIG. 1.

Probabilistic sensitivity analysis for 9 cohort models. Values on the x-axis are QALYs and those on the y-axis are cost in USD. Figure is available in color online only.

Sensitivity Analysis

In a 1-way sensitivity analysis, rupture risk thresholds associated with cost-effectiveness varied between 0.008 and 0.019. This was done at a willingness to pay 100,000 USD per QALY by patient age and endovascular proportion (Table 4). If annual rupture risk exceeded this threshold, the ICER of treatment was less than 100,000 USD per QALY and was found to be cost-effective.

TABLE 4.

One-way sensitivity analysis on lower threshold of annual risk of UIA rupture where ICER < 100,000 USD/QALY

Age of Cohort, YrsProportion of ET/MT
60%/40%70%/30%80%/20%
550.0080.0060.005
650.0120.0100.008
750.0250.0220.019

Patient age varied over a range of 50 to 100 years at the time a treatment decision was made. Treatment was cost-effective for patients younger than 67.75, younger than 70, and younger than 72 years at centers where an endovascular modality was used at 60% proportion, at 70% proportion, and at 80% proportion, respectively (Fig. 2).

FIG. 2.
FIG. 2.

Sensitivity analysis of age threshold where ICER < 100,000 USD/QALY. Figure is available in color online only.

The annual rupture risk associated with unsecured aneurysms was varied over a range of 0% and 10% while keeping other variables fixed. Preventive treatment was the most optimal strategy at an annual rupture risk of 6% or greater over conservative management in a patient cohort aged 55 years. In cohorts of patients aged 65 years, preventive treatment was most optimal when the annual rupture risk exceeded 9%. For cohorts aged 75 years, a conservative approach remained the most optimal management within this range of rupture risks.

Discussion

This study demonstrated that preventive aneurysm treatment consistently increases health utility when compared with conservative treatment. Additionally, a higher proportion of endovascular treatment was more cost-effective. The American Heart Association stated that when the risk of hemorrhage is low, such as in small asymptomatic UIAs, observation is a reasonable alternative to surgical treatment.10 This is especially true in the elderly population with comorbidities.10 Additionally, the majority of aneurysms in the population are small in size.20 In recent years, the number of hospitalizations associated with preventive treatment of UIAs has significantly increased.6,20 Preventive endovascular treatments are responsible for this increase.20 Interestingly, the upward trend of preventive treatment has not resulted in decreasing the rate of aSAH deaths.21

Hospitalization charges are lower with endovascular treatment.20 However, endovascular treatment creates additional costs not encountered by clipping due to higher rates of re-treatment and follow-up cerebral angiograms, creating a chronic disease.15,22,23 Overall, despite lower mean hospitalization charges, endovascular treatment has greater economic burden.20 Maud et al. concluded that endovascular treatment was more costly but resulted in higher QALYs (better outcomes) compared with clipping.15 This result was obtained using clinical data and quality-of-life values from the International Subarachnoid Aneurysm Trial (ISAT), which included aneurysms that were suitable for treatment via either surgical or endovascular technique.15

Since ISAT, the endovascular world is evolving at a rapid pace unlike microsurgical clipping.23 The improving technology and costs may influence cost-effectiveness studies.21,23 Decreased disability rates with coiling might also decrease costs.23 However, microsurgical clipping and endovascular treatment are complementary and both are essential for cerebrovascular practice. Not all aneurysms are equally suitable for endovascular treatment and microsurgical clipping. This was illustrated in the Barrow Ruptured Aneurysm Trial in which 38% of the patients assigned to coiling crossed over to clipping.24–26 Only 1.9% of patients assigned to clipping crossed over to coiling.24–26 Malhotra et al. compared different imaging follow-up strategies and coiling without microsurgical clipping.5 Greving et al. compared three separate strategies in which all patients would receive microsurgical clipping, endovascular treatment, or conservative treatment.13

Within our analysis, when annual aneurysm rupture risk exceeds 6% in patients aged 55 years or 9% in patients aged 65 years, the decision to treat leads to both lower lifetime costs and improved health outcomes. These findings are similar to those of a previous analysis by Malhotra et al. who identified that coiling becomes cost-effective compared with surveillance imaging when the rupture rate is greater than 7.1% in the elderly.5

Our results demonstrate an annual rupture risk threshold associated with cost-effectiveness varying between 0.8% and 1.9% for all cohorts modeled age 55, 65, and 75 years. A higher proportion of endovascular treatment and younger age lowered the rupture risk threshold of cost-effectiveness. Many studies have reported the natural history of unruptured aneurysms. A recent meta-analysis showed an overall annual rupture rate of 0.4% for aneurysms smaller than than 7 mm.10,27 Extrapolating from our results, the treatment of aneurysms smaller than 7 mm is not cost-effective. Preventive aneurysm treatment has been identified to be cost-effective if the patient had a life expectancy of 13 additional years.28

A notable limitation of previous studies is the unknown utility of patients who were aware of an untreated aneurysm and chose the conservative approach.5,13 One of the strengths of the present study is the use of such utility collected prospectively in patients who harbor a UIA.

To achieve the lowest costs possible within conservative management, we assumed no imaging surveillance in those patients undergoing conservative management. Conservative management was defined as treatment of a UIA until aSAH. This decision was made due to their being no well-published data on annual treatment rates due to aneurysm changes on follow-up imaging.

In the interpretation of this study, certain limitations must be considered. QALYs were collected prospectively from a Canadian population while studies reporting a population from the United States were used. The variations in proportions between endovascular treatment and microsurgical treatment were made to reflect the differences in practices worldwide, which is influenced by local experience and neurosurgeon training. It is possible that complication rates vary among the different proportions as aneurysms might be treated with a less balanced approach. Due to the prespecified proportion of endovascular treatment and microsurgical treatment, a 1-way sensitivity analysis varying complication rates of these treatments was not feasible within this model. However, second degree uncertainties regarding estimation of complications are reflected in our PSA, which varies this risk around the expected rate using a Dirichlet distribution. A limitation within our sensitivity analysis is that measured utilities reflected implicit concern of aneurysm rupture in patients with untreated aneurysms, which led to persistently higher utility of treatment even at a rupture risk of zero. Estimates for bleeding after treatment and re-treatment that are available in the literature are based on relatively short follow-up (< 10 years). These rates likely represent an overestimation. Rigorous studies outlining postclipping rupture rates are lacking in the literature. Clinical estimates were derived from large cohorts and meta-analyses from the literature. Therefore, the usage of those clinical estimates brings along with them the limitations of those studies such as selection bias. If better clinical estimates were to become available, an updated cost-effectiveness analysis study should be performed.

Certain assumptions were made to make the model feasible. For example, it is possible that in certain cases a repeat or subsequent surgery has outcomes that are different from those of the first surgery. Estimates for re-treatment and rebleeding after clipping are based on small sample size or short follow-up. The assumption that clipping is curative and never requires re-treatment is an underestimation. However, rebleeding or re-treatment is extremely rare, and the rate is very close to zero.

Conclusions

In this cost-effectiveness analysis of preventive treatment of UIA, different proportions of endovascular treatment to microsurgical clipping have been compared with conservative treatment. Preventive treatment of aneurysms led to higher utility compared with conservative management. A higher proportion of endovascular treatment and treatment at a younger age were more cost-effective. As endovascular technology continues to evolve with different costs and outcomes, updated cost-effectiveness studies should be performed to aid health policy and decision-making.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Dandurand, Zhou. Acquisition of data: Dandurand. Analysis and interpretation of data: Dandurand, Zhou. Drafting the article: Dandurand, Zhou, Prakash. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Dandurand. Statistical analysis: Dandurand, Zhou. Study supervision: Dandurand.

Supplemental Information

Online-Only Content

Supplemental material is available with the online version of the article.

References

  • 1

    Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 2011;10(7):626636.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Lawton MT, Vates GE. Subarachnoid hemorrhage. N Engl J Med. 2017;377(3):257266.

  • 3

    Wiebers DO, Whisnant JP, Huston J III, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362(9378):103110.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Algra AM, Lindgren A, Vergouwen MDI, et al. Procedural clinical complications, case-fatality risks, and risk factors in endovascular and neurosurgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis. JAMA Neurol. 2019;76(3):282293.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Malhotra A, Wu X, Forman HP, et al. Management of unruptured intracranial aneurysms in older adults: a cost-effectiveness analysis. Radiology. 2019;291(2):411417.

  • 6

    Silva NA, Shao B, Sylvester MJ, et al. Unruptured aneurysms in the elderly: perioperative outcomes and cost analysis of endovascular coiling and surgical clipping. Neurosurg Focus. 2018;44(5):E4.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Lindgren A, Vergouwen MD, van der Schaaf I, et al. Endovascular coiling versus neurosurgical clipping for people with aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2018;8(8):CD003085.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    National Center for Health Statistics. Life tables. CDC.gov. June 19, 2019. Accessed August 11, 2019. https://www.cdc.gov/nchs/products/life_tables.htm

  • 9

    Huhtakangas J, Lehto H, Seppä K, et al. Long-term excess mortality after aneurysmal subarachnoid hemorrhage: patients with multiple aneurysms at risk. Stroke. 2015;46(7):18131818.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Thompson BG, Brown RD Jr, Amin-Hanjani S, et al. Guidelines for the management of patients with unruptured intracranial aneurysms: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(8):23682400.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Nieuwkamp DJ, Setz LE, Algra A, et al. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol. 2009;8(7):635642.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Hammer A, Steiner A, Ranaie G, et al. Impact of comorbidities and smoking on the outcome in aneurysmal subarachnoid hemorrhage. Sci Rep. 2018;8(1):12335.

  • 13

    Greving JP, Rinkel GJE, Buskens E, Algra A. Cost-effectiveness of preventive treatment of intracranial aneurysms: new data and uncertainties. Neurology. 2009;73(4):258265.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Daileda T, Vahidy FS, Chen PR, et al. Long-term retreatment rates of cerebral aneurysms in a population-level cohort. J Neurointerv Surg. 2019;11(4):367372.

  • 15

    Maud A, Lakshminarayan K, Suri MFK, et al. Cost-effectiveness analysis of endovascular versus neurosurgical treatment for ruptured intracranial aneurysms in the United States. J Neurosurg. 2009;110(5):880886.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Qureshi AI, Vazquez G, Tariq N, et al. Impact of International Subarachnoid Aneurysm Trial results on treatment of ruptured intracranial aneurysms in the United States. Clinical article. J Neurosurg. 2011;114(3):834841.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    CPT codes and fees: radiology (70010-79999). North Carolina Industrial Commission. Accessed December 18, 2020.http://www.ic.nc.gov/ncic/pages/70000.htm

  • 18

    Ali M, MacIsaac R, Quinn TJ, et al. Dependency and health utilities in stroke: data to inform cost-effectiveness analyses. Eur Stroke J. 2017;2(1):7076.

  • 19

    Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796797.

  • 20

    Huang MC, Baaj AA, Downes K, et al. Paradoxical trends in the management of unruptured cerebral aneurysms in the United States: analysis of nationwide database over a 10-year period. Stroke. 2011;42(6):17301735.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Jalbert JJ, Isaacs AJ, Kamel H, Sedrakyan A. Clipping and coiling of unruptured intracranial aneurysms among medicare beneficiaries, 2000 to 2010.Stroke. 2015;46(9):24522457.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Campi A, Ramzi N, Molyneux AJ, et al. Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the International Subarachnoid Aneurysm Trial (ISAT). Stroke. 2007;38(5):15381544.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Zhang X, Li L, Hong B, et al. A systematic review and meta-analysis on economic comparison between endovascular coiling versus neurosurgical clipping for ruptured intracranial aneurysms. World Neurosurg.2018;113:269275.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Spetzler RF, McDougall CG, Zabramski JM, et al. Ten-year analysis of saccular aneurysms in the Barrow Ruptured Aneurysm Trial. J Neurosurg. 2020;132(3):771776.

  • 25

    Spetzler RF, McDougall CG, Zabramski JM, et al. The Barrow Ruptured Aneurysm Trial: 6-year results. J Neurosurg. 2015;123(3):609617.

  • 26

    McDougall CG, Spetzler RF, Zabramski JM, et al. The Barrow Ruptured Aneurysm Trial. J Neurosurg. 2012;116(1):135144.

  • 27

    Wermer MJH, van der Schaaf IC, Algra A, Rinkel GJE. Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis. Stroke. 2007;38(4):14041410.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    King JT Jr, Glick HA, Mason TJ, Flamm ES. Elective surgery for asymptomatic, unruptured, intracranial aneurysms: a cost-effectiveness analysis. J Neurosurg. 1995;83(3):403412.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Greving JP, Wermer MJH, Brown RD, et al. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol. 2014;13(1):5966.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Huang J, van Gelder JM. The probability of sudden death from rupture of intracranial aneurysms: a meta-analysis. Neurosurgery. 2002;51(5):11011107.

  • 31

    Korja M, Kivisaari R, Rezai Jahromi B, Lehto H. Natural history of ruptured but untreated intracranial aneurysms. Stroke. 2017;48(4):10811084.

  • 32

    Naggara ON, White PM, Guilbert F, et al. Endovascular treatment of intracranial unruptured aneurysms: systematic review and meta-analysis of the literature on safety and efficacy. Radiology. 2010;256(3):887897.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Supplementary Materials

  • Collapse
  • Expand

Selected panels from a figure in Satzer et al. (pp 1742–1751).

  • FIG. 1.

    Probabilistic sensitivity analysis for 9 cohort models. Values on the x-axis are QALYs and those on the y-axis are cost in USD. Figure is available in color online only.

  • FIG. 2.

    Sensitivity analysis of age threshold where ICER < 100,000 USD/QALY. Figure is available in color online only.

  • 1

    Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 2011;10(7):626636.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Lawton MT, Vates GE. Subarachnoid hemorrhage. N Engl J Med. 2017;377(3):257266.

  • 3

    Wiebers DO, Whisnant JP, Huston J III, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362(9378):103110.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Algra AM, Lindgren A, Vergouwen MDI, et al. Procedural clinical complications, case-fatality risks, and risk factors in endovascular and neurosurgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis. JAMA Neurol. 2019;76(3):282293.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Malhotra A, Wu X, Forman HP, et al. Management of unruptured intracranial aneurysms in older adults: a cost-effectiveness analysis. Radiology. 2019;291(2):411417.

  • 6

    Silva NA, Shao B, Sylvester MJ, et al. Unruptured aneurysms in the elderly: perioperative outcomes and cost analysis of endovascular coiling and surgical clipping. Neurosurg Focus. 2018;44(5):E4.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Lindgren A, Vergouwen MD, van der Schaaf I, et al. Endovascular coiling versus neurosurgical clipping for people with aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2018;8(8):CD003085.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    National Center for Health Statistics. Life tables. CDC.gov. June 19, 2019. Accessed August 11, 2019. https://www.cdc.gov/nchs/products/life_tables.htm

  • 9

    Huhtakangas J, Lehto H, Seppä K, et al. Long-term excess mortality after aneurysmal subarachnoid hemorrhage: patients with multiple aneurysms at risk. Stroke. 2015;46(7):18131818.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Thompson BG, Brown RD Jr, Amin-Hanjani S, et al. Guidelines for the management of patients with unruptured intracranial aneurysms: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(8):23682400.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Nieuwkamp DJ, Setz LE, Algra A, et al. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol. 2009;8(7):635642.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Hammer A, Steiner A, Ranaie G, et al. Impact of comorbidities and smoking on the outcome in aneurysmal subarachnoid hemorrhage. Sci Rep. 2018;8(1):12335.

  • 13

    Greving JP, Rinkel GJE, Buskens E, Algra A. Cost-effectiveness of preventive treatment of intracranial aneurysms: new data and uncertainties. Neurology. 2009;73(4):258265.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Daileda T, Vahidy FS, Chen PR, et al. Long-term retreatment rates of cerebral aneurysms in a population-level cohort. J Neurointerv Surg. 2019;11(4):367372.

  • 15

    Maud A, Lakshminarayan K, Suri MFK, et al. Cost-effectiveness analysis of endovascular versus neurosurgical treatment for ruptured intracranial aneurysms in the United States. J Neurosurg. 2009;110(5):880886.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Qureshi AI, Vazquez G, Tariq N, et al. Impact of International Subarachnoid Aneurysm Trial results on treatment of ruptured intracranial aneurysms in the United States. Clinical article. J Neurosurg. 2011;114(3):834841.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    CPT codes and fees: radiology (70010-79999). North Carolina Industrial Commission. Accessed December 18, 2020.http://www.ic.nc.gov/ncic/pages/70000.htm

  • 18

    Ali M, MacIsaac R, Quinn TJ, et al. Dependency and health utilities in stroke: data to inform cost-effectiveness analyses. Eur Stroke J. 2017;2(1):7076.

  • 19

    Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796797.

  • 20

    Huang MC, Baaj AA, Downes K, et al. Paradoxical trends in the management of unruptured cerebral aneurysms in the United States: analysis of nationwide database over a 10-year period. Stroke. 2011;42(6):17301735.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Jalbert JJ, Isaacs AJ, Kamel H, Sedrakyan A. Clipping and coiling of unruptured intracranial aneurysms among medicare beneficiaries, 2000 to 2010.Stroke. 2015;46(9):24522457.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Campi A, Ramzi N, Molyneux AJ, et al. Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the International Subarachnoid Aneurysm Trial (ISAT). Stroke. 2007;38(5):15381544.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Zhang X, Li L, Hong B, et al. A systematic review and meta-analysis on economic comparison between endovascular coiling versus neurosurgical clipping for ruptured intracranial aneurysms. World Neurosurg.2018;113:269275.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Spetzler RF, McDougall CG, Zabramski JM, et al. Ten-year analysis of saccular aneurysms in the Barrow Ruptured Aneurysm Trial. J Neurosurg. 2020;132(3):771776.

  • 25

    Spetzler RF, McDougall CG, Zabramski JM, et al. The Barrow Ruptured Aneurysm Trial: 6-year results. J Neurosurg. 2015;123(3):609617.

  • 26

    McDougall CG, Spetzler RF, Zabramski JM, et al. The Barrow Ruptured Aneurysm Trial. J Neurosurg. 2012;116(1):135144.

  • 27

    Wermer MJH, van der Schaaf IC, Algra A, Rinkel GJE. Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis. Stroke. 2007;38(4):14041410.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    King JT Jr, Glick HA, Mason TJ, Flamm ES. Elective surgery for asymptomatic, unruptured, intracranial aneurysms: a cost-effectiveness analysis. J Neurosurg. 1995;83(3):403412.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Greving JP, Wermer MJH, Brown RD, et al. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol. 2014;13(1):5966.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Huang J, van Gelder JM. The probability of sudden death from rupture of intracranial aneurysms: a meta-analysis. Neurosurgery. 2002;51(5):11011107.

  • 31

    Korja M, Kivisaari R, Rezai Jahromi B, Lehto H. Natural history of ruptured but untreated intracranial aneurysms. Stroke. 2017;48(4):10811084.

  • 32

    Naggara ON, White PM, Guilbert F, et al. Endovascular treatment of intracranial unruptured aneurysms: systematic review and meta-analysis of the literature on safety and efficacy. Radiology. 2010;256(3):887897.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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