Costs and Cost-Effectiveness of Carotid Stenting Versus...

Costs and Cost-Effectiveness of Carotid Stenting VersusEndarterectomy for Patients at Standard Surgical RiskResults From the Carotid Revascularization Endarterectomy Versus

Stenting Trial (CREST)

Katherine R. Vilain, MPH*; Elizabeth A. Magnuson, ScD*; Haiyan Li, MA; Wayne M. Clark, MD;Richard J. Begg, MD; Albert D. Sam II, MD; W. Charles Sternbergh III, MD;

Fred A. Weaver, MD, MMM; William A. Gray, MD; Jenifer H. Voeks, PhD; Thomas G. Brott, MD;David J. Cohen, MD, MSc; on behalf of the CREST Investigators

Background and Purpose—The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstratedsimilar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy(CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA.Given the large number of patients who are candidates for these procedures, an understanding of their relative cost andcost-effectiveness may have important implications for health care policy and treatment guidelines.

Methods—We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trialparticipants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-levelhealth use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated tothe CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups.

Results—Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costswere lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus$14 816; mean difference, $239/patient; 95% CI for difference, �$297 to $775). Neither follow-up costs after dischargenor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year timehorizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction inquality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated thatCEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-yeargained in 54% of samples, whereas CAS was economically attractive in 46%.

Conclusions—Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs andquality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice,these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatmentoptions for carotid artery stenosis in patients at standard risk for surgical complications.

Clinical Trial Registration—URL: http://clinicaltrials.gov. Unique Identifier: NCT00004732.(Stroke. 2012;43:2408-2416.)

Key Words: economics � endarterectomy � prevention � quality of life � stenting � stroke care

Major stroke is associated with high medical care costs andreductions in life expectancy and quality of life.1–10

Carotid endarterectomy (CEA) has been shown in several trialsto be superior to medical management for the prevention of

stroke in select patients with symptomatic or asymptomatic carotidartery stenosis.11,12 More recently, carotid artery stenting (CAS)with the use of an embolic protection device has been introducedas a less invasive approach to carotid revascularization.

Received April 19, 2012; accepted June 8, 2012.From the Saint Luke’s Mid America Heart Institute, Kansas City, MO (K.R.V., E.A.M., H.L., D.J.C.); University of Missouri, Kansas City, MO

(E.A.M., D.J.C.); Oregon Health and Science University, Portland, OR (W.M.C.); Heritage Valley Health System, Heart and Vascular Center, Beaver,PA (R.J.B.); Vascular Specialty Center, Baton Rouge, LA (A.D.S.); Ochsner Health System, New Orleans, LA (W.C.S.); the University of SouthernCalifornia, Los Angeles, CA (F.A.W.); Columbia University, New York, NY (W.A.G.); Medical University of South Carolina, MUSC Stroke Center,Charleston, SC (J.H.V.); and the Mayo Clinic, Jacksonville, FL (T.G.B.).

*K. Vilain and E. Magnuson are equal contributors.The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.112.

661355/-/DC1.Correspondence to David J. Cohen, MD, MSc, Saint Luke’s Mid America Heart Institute, 4401 Wornall Road, Kansas City, MO 64111. E-mail

[email protected]© 2012 American Heart Association, Inc.

Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.112.661355

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http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.112.661355/-/DC1

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In patients for whom surgery poses an increased risk, theStenting and Angioplasty with Protection in Patients at HighRisk of Endarterectomy (SAPPHIRE) trial demonstratedCAS to be clinically noninferior to CEA with a favorablecost-effectiveness ratio.13,14 In patients at standard risk forsurgical complications, the Carotid Revascularization Endar-terectomy versus Stenting Trial (CREST) found no signifi-cant difference in the primary clinical outcome of stroke,myocardial infarction (MI), or death within the periproce-dural period or any ipsilateral stroke thereafter, although therewas a significantly higher rate of periprocedural stroke withCAS and a significantly higher rate of periprocedural MI withCEA.15 Given the large number of patients who are candi-dates for these alternative procedures, an understanding oftheir relative cost and cost-effectiveness may have importantimplications for healthcare policy and treatment guidelines.We therefore performed a prospective economic evaluationalongside the CREST trial in which we used empirical dataon healthcare costs and health utilities and clinical outcomesfrom the trial as inputs to a Markov state-transition model thatwas used as the basis for formal cost-effectiveness analysis.

MethodsPatient PopulationBetween December 2000 and July 2008, 2522 patients with symp-tomatic or asymptomatic carotid stenosis who were judged to beclinically and anatomically suitable for both CAS and CEA wereenrolled in the CREST trial (ClinicalTrials.gov numberNCT00004732) at 108 US and 9 Canadian centers. Full details of theinclusion and exclusion criteria as well as the complete studyprotocol have been published previously.15,16

Eligible patients were randomized in a 1:1 ratio to CAS (n�1271)or CEA (n�1251). After excluding 20 patients due to suspectedscientific misconduct, the primary analysis of clinical outcomes wasconducted on a data set that included 2502 patients (n�1262 CAS;1240 CEA).15 For the economic study, we defined 2 analyticpopulations: a modified intention-to-treat (ITT) population thatincluded all patients except those who declined their assignedprocedure after randomization (n�1213 CAS; 1193 CEA) and anAssigned Treatment Received population that included only thosepatients in whom the assigned treatment was actually performedwithout crossover treatment during the periprocedural period(n�1136 CAS; 1184 CEA; online-only Data Supplement FigureI). The modified ITT population was considered the primarypopulation for the cost and cost-effectiveness analyses unlessotherwise specified.

Estimation of In-Trial CostsMedical care costs for treatment of cerebrovascular disease and itsdirect and indirect complications were assessed for all patients overa 1-year follow-up period using a combination of resource-basedcosts and hospital billing data as previously described.17 All costswere assessed in year 2008 dollars or converted to 2008 dollars usingthe medical care component of the Consumer Price Index.18

Index ProceduresDetailed resource use was recorded for each procedure, and costswere calculated as the product of resource use and unit cost for eachcomponent. Acquisition costs for each item were estimated using2008 acquisition costs from a sample of study centers (Table 1). Thestudy stent (RX ACCULINK Carotid Stent System; Abbott Vascu-lar, Inc, Santa Clara, CA) was assigned an acquisition cost of $2107,and the embolic protection device (RX ACCUNET Embolic Protec-tion System; Abbott Vascular, Inc) was assigned an acquisition costof $1505 based on national average pricing data obtained from the

IMS Hospital Supply Index as of September 2010. Ancillary costsfor the catheterization laboratory or interventional radiology suite(for CAS procedures) and for the operating room (for CEA proce-dures) included overhead and depreciation, nonphysician personnel,and general supplies required for each procedure and were estimatedbased on a survey of study hospitals.

Procedure-related physician fees for the primary operator and firstassistant (where applicable) were calculated using national averagerates from the 2008 Medicare Fee Schedule and included the cost forthe revascularization procedure plus the cost of diagnostic cerebralangiography if applicable. Anesthesiologist fees for CEA procedureswere calculated based on measured procedure duration according tothe Medicare fee schedule.

Postprocedure Hospital CareCosts for all other aspects of care during the initial hospitalizationwere estimated based on hospital billing data. Itemized hospital billsand UB-92 or UB-04 forms (summary billing statements) wereobtained for 577 CAS patients and 637 CEA patients. After exclud-ing any charges associated with the index procedure, postprocedurehospital costs were calculated by multiplying the remaining hospitalcharges by year- and hospital-specific revenue code-level cost-to-charge ratios obtained from each center’s Medicare Cost Report.17

For index hospitalizations without available billing data(n�1203), postprocedural hospital costs were estimated using alinear regression model developed from hospital admissions for

Table 1. Index Procedural Resource Use and Costs (AssignedTreatment Received Population)

Mean Value(Median) Unit Cost

CAS resource use (n�1136)

Procedure duration, min 69�31 (62) $17.24/min

Study stents 1.01�0.30 (1) $2107

Embolus protectiondevices/filters

0.95�0.38 (1) $1505

Guiding catheters 1.06�0.81 (1) $50

Interventional guidewires 1.47�1.12 (1) $92.55

IVUS catheters 0.04�0.23 (0) $825

Balloon catheters 1.67�0.69 (2) $270

Pulmonary artery catheters 0.01�0.09 (0) $48

Temporary pacing catheters 0.002�0.04 (0) $85

IABPs 0.05�0.22 (0) $1440

Contrast volume, mL 147�62 (140) $0.13–$0.44/mL

CEA resource use (n�1184)

Procedure duration, minutes 171�55 (165) $23.75/min

Patches/grafts 0.62�0.48 (1) $106.50

Shunts 0.57�0.48 (1) $399

CAS procedure cost

Room/overhead, supplies,nonphysician personnel

$2284�541 (2172)

Devices $4510�872 (4320)

Total $6794�1109 (6544)

CEA procedure cost

Room/overhead, supplies,nonphysician personnel

$5476�1315 (5344)

Devices $293�213 (399)

Total $5769�1343 (5561)

CAS indicates carotid stenting; IVUS, intravascular ultrasound; CEA, carotidendarterectomy; IABP, intra-aortic balloon pump.

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which billing information was available (R2�0.51). Covariatesincluded in the final model were treatment group, sex, length of stay(intensive care unit and nonintensive care unit), previous coronaryartery bypass graft, and procedure-related complications (MI, minorstroke, major stroke, bleeding). Inclusion of additional covariatesand alternative model structures did not improve model fit.

Rehospitalization CostsDetailed resource use was collected for repeat carotid revasculariza-tion procedures, and costs were assigned to those admissions usingthe same approach as that developed for the estimation of indexhospitalization costs. Subsequent hospitalizations associated withMI, transient ischemic attack, stroke, and death events were eachmapped to a diagnosis-related group (by a coder blinded to treatmentassignment, and costs for each hospital admission were assignedbased on the corresponding national average Medicare reimburse-ment rates for 2008.19 Physician fees for rehospitalizations wereestimated as a percentage of hospital costs according to diagnosis-related group as described previously.20,21

Statistical AnalysisDiscrete data are reported as frequencies, and continuous data arereported as mean�SD and median. Discrete variables were com-pared by Fisher exact test. Normally distributed continuous variableswere compared by Student t test, and nonnormally distributed datawere compared by the Wilcoxon rank-sum test. Given the skeweddistribution of length of stay and cost data, we used nonparametricbootstrapping (1000 replicates) to estimate probability values and95% CIs for differences in length of stay and costs between the 2treatment arms.22 All statistical analyses were performed using SASVersion 9.2 (SAS Institute, Inc, Cary, NC). A probability value�0.05 was considered statistically significant for all comparisons.

Cost-Effectiveness AnalysisCost-effectiveness of CAS versus CEA was assessed in terms of costper quality-adjusted life-year (QALY) gained over a 10-year timehorizon from the perspective of the US healthcare system. Becauseresource use and cost data were collected only for the first year offollow-up in CREST, and there were differences between CAS andCEA for prognostically important events, it was necessary toextrapolate the observed results beyond the trial period to providemeaningful cost-effectiveness results. We therefore developed astate-transition (Markov) model to project clinical outcomes, qualityof life, survival, and costs beyond the trial period. Our generalapproach was to base this model to the greatest extent on theobserved results of the CREST trial. The model structure and theassumptions for transition probabilities, costs, and utility weights(along with their underlying distributions and data sources) aresummarized in the online-only Data Supplement. The model wasprogrammed using TreeAge Pro 2011 (TreeAge, Inc, Williamstown,MA) and structured as a microsimulation with patients sampled froman underlying population that mirrored the age and symptomaticstatus distributions of the CREST trial population.

Model Calibration and AnalysesModel calibration was confirmed by comparing the projected1-month and 1-year costs and clinical event rates against theobserved trial results (results within 3% of observed for all majoroutcomes; see online-only Data Supplement Table I). For thepurposes of cost-effectiveness analysis, all future costs, life-years,and QALYs were discounted at 3% per year, consistent with currentguidelines.23 The incremental cost-effectiveness ratio (ICER) forCAS versus CEA was calculated by dividing the difference in meandiscounted costs by the difference in mean quality-adjusted lifeexpectancy for the 2 treatment strategies. The overall impact ofuncertainty was assessed by means of probabilistic sensitivityanalysis in which all model parameters were sampled from theirappropriate distributions over 1000 runs. The results of these analysesare displayed graphically as a joint distribution of the incremental costand effectiveness of CAS versus CEA in the cost-effectiveness plane. In

addition to the primary analysis for the overall trial population, weperformed prespecified subgroup analyses for the asymptomatic andsymptomatic CREST populations.

ResultsStudy PopulationOf the 1262 patients randomized to CAS, 1213 (96.1%)underwent attempted CAS and 1136 (89.4%) had CASperformed as assigned. Of the 1240 patients randomized toCEA, 1193 (95.4%) underwent attempted CEA, and 1184(94.6%) had CEA performed as assigned (online-only DataSupplement Figure I). Baseline characteristics did not differbetween treatment groups for either the modified ITT or theAssigned Treatment Received populations (online-only DataSupplement Table II). The prevalence of symptomatic carotidstenosis was 53% for each treatment group for both themodified ITT and Assigned Treatment Received populations.

Index Hospitalization Resource Use and CostsFor the modified ITT population, 1136 of the 1213 patientsrandomized to CAS received CAS only; 8 underwent at-tempted CAS followed by CEA, and 40 underwent CEAonly. The remaining 29 patients underwent carotid andcerebral angiography only. The main reason for crossover toCEA was anatomic unsuitability for CAS. Of the 1193modified ITT patients randomized to CEA, 1184 underwentCEA and 9 received only angiography; no patients in theCEA group underwent CAS.

Resource use and costs for the index procedures aresummarized in Table 1. A mean of 1.01 stents and 0.95embolic protection devices were used in the CAS arm withtotal device-related costs of $4510/patient. Although operat-ing room costs (including overhead, depreciation, supplies,and nonphysician personnel) were substantially higher forCEA than for CAS, after including device-related costs, totalprocedural costs were higher with CAS ($6794 versus $5769,P�0.001). On the other hand, physician fees were higherwith CEA ($1951 versus $1514, P�0.001), mainly due toanesthesiology services.

Periprocedural event rates, postprocedural length of stay,and overall costs for the index hospitalization are summarizedin Table 2. Within the modified ITT population, rates ofperiprocedural stroke were higher for CAS, whereas rates ofMI were higher for CEA. Mean postprocedure length of staywas 0.4 days longer in the CEA arm (3.0 versus 2.6 days;P�0.002) with significant differences in both intensive careunit and nonintensive care unit days. Postprocedural hospitalcosts were $363/patient higher for CEA ($7122 versus $6759;P�0.927). Overall costs for the initial hospitalization (includ-ing procedural, postprocedural, and physician costs) wereslightly but nonsignificantly higher with CAS than with CEA($15 055 versus $14 816; 95% CI for difference, $297 less to$775 more; P�0.185).

One-Year Clinical Outcomes and CostsOne-year rates of rehospitalization for major cardiovascularevents and their associated costs are shown in Table 3.Overall rates of hospitalization for repeat carotid revascular-ization (either by CAS or CEA) did not differ significantly for

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the CAS versus CEA groups. As a result, mean follow-upcosts did not differ significantly between the CAS and CEAgroups ($1321 versus $1293; P�0.441). Total 1-year costsincluding the initial revascularization procedures were $267/patient higher for CAS, but this difference was not statisti-cally significant ($16 375 versus $16 108; 95% CI for differ-ence, $366 less to $961 more; P�0.223).

Utility Weights and In-Trial Quality-AdjustedLife ExpectancyThere were small but statistically significant differences inutility weights favoring CAS at both the 2-week and monthtime points but no differences at 1 year (Table 4). Quality-adjusted life expectancy over the first year of follow-up wasvirtually identical for the CAS and CEA groups (0.704 versus

Table 2. Index Hospitalization Events, Resource Use, and Costs (Modified ITT Population)

CAS (n�1213) CEA (n�1193)Difference(95% CI)

PValue

Death, % 0.3 0.2 0.2 (�0.2 to 0.6) 0.687

Stroke, % 3.0 1.3 1.6 (0.5–2.8) 0.006

Major 0.5 0.3 0.2 (�0.4 to 0.7) 0.753

Minor 2.5 1.0 1.5 (0.4–2.5) 0.006

MI, % 1.5 2.9 �1.4 (�2.6 to �0.3) 0.016

Unplanned CAS, % 0.2 0.0 0.2 (0.0–0.5) 0.250

Unplanned CEA, % 0.1 0.3 �0.3 (�0.6 to 0.1) 0.215

Post-Procedural LOS, d

Non-ICU 1.9�3.2 �1� 2.2�4.1 �1� 0.2 (�0.55 to 0.06) 0.053

ICU 0.7�1.1 �0� 0.8�1.4 �1� �0.1 (�0.24 to 0.04) 0.002

Total 2.6�3.3 �1� 3.0�4.5 �1� �0.4 (�0.70 to 0.06) 0.011

Index hospitalization costs

Procedural $6782�1412 �6554� $5743�1370 �5553� $1039 (926–1148) �0.001

Postprocedural $6759�4815 �5012� $7122�6895 �4926� �$363 (�831 to 107) 0.927

Physician fee $1514�446 �1471� $1951�693 �1876� �$437 (�485 to �394) �0.001

Total index hospitalization $15 055�5539 �13 347� $14 816�7709 �12 777� $239 (�302 to 778) 0.185

Values in brackets are medians.ITT indicates intention-to-treat; CAS, carotid stenting; CEA, carotid endarterectomy; MI, myocardial infarction; LOS, length of stay;

ICU, intensive care unit.

Table 3. One-Year Follow-Up Events and Costs (Modified ITT Population)

CAS(n�1213)

CEA(n�1193)

Difference(95% CI)

PValue

Events after initial hospitalization

Stroke, % 3.0 2.1 0.9 (�0.5 to 2.2) 0.173

Major, % 1.6 1.5 0.1 (�0.9, 1.0) 0.907

Minor, % 1.4 0.6 0.8 (�0.0 to �1.6) 0.044

MI,* % 0.3 0.5 �0.2 (�0.7 to 0.3) 0.545

Repeat revascularization, % 4.2 5.8 �1.6 (�3.3 to 0.2) 0.076

CAS, % 2.1 1.8 0.3 (�0.8 to 1.4) 0.598

CEA, % 2.1 3.9 �1.8 (�3.2 to �0.4) 0.010

Death, % 1.0 0.7 0.3 (�0.4 to 1.0) 0.388

TIA, % 0.9 0.5 0.4 (�0.3 to 1.1) 0.236

Costs to 1 y

Total index hospitalization $15 055�5539 �13 347� $14 816�7709 �12 777� $239 (�302 to 778) 0.185

Discharge to 1 y $1321�4827 �0� $1293�4502 �0� $28 (�335 to 396) 0.441

Cumulative to 1 y $16 375�7730 �13 637� $16 108�9030 �13 112� $267 (�366 to 961) 0.223

Values in brackets are medians.ITT indicates intention-to-treat; CAS, carotid stenting; CEA, carotid endarterectomy; MI, myocardial infarction; TIA, transient

ischemic attack.*MI was reported only when it occurred within 30 d of the index procedure.



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0.708; mean difference, 0.005; 95% CI for difference,�0.006 to 0.153; P�0.403). Linear regression analysis dem-onstrated that the occurrence of major stroke was associatedwith a significant reduction in utilities among survivingpatients with disutility values of 0.10 at 1 month and 0.06 at12 months. Minor stroke also had a sustained effect onfollow-up utilities with estimated disutility values of 0.02 at 1month and 0.03 at 12 months. Neither MI nor cranial nerveinjury had a detectable impact on utilities at either time point.

Cost-Effectiveness AnalysisBased on the observed 1-year trial results alone, CAS wasassociated with a small increase in cost ($267) and a smalldecrease in QALYs (0.005), rendering CEA an economicallydominant therapy (ie, associated with both lower cost andgreater effectiveness than CAS) in the short term. The resultsof our 10-year cost-effectiveness analysis based on thetrial-based Markov model are summarized in Table 5 and theFigure A–C. For an overall population similar to that enrolledin CREST (mean age, 69 years; 53% symptomatic), ourmodel projected that over a 10-year time horizon CEA wouldbe an economically dominant strategy with net cost savingsof $524 and an increase in quality-adjusted life expectancy of0.008 years. Probabilistic sensitivity analysis demonstratedconsiderable uncertainty in the long-term results, however(Figure A). CEA was economically dominant in 34.2% ofbootstrap replicates, and CAS was economically dominant in6.2%. The probability that CEA was economically attractive

at a willingness-to-pay threshold of $50 000/QALY gainedwas 54.4%.

For symptomatic patients, CEA was projected to be adominant approach with projected cost savings of $448/patient and a gain in quality-adjusted life expectancy of 0.017years in the base case analysis. The probability that CEA waseconomically attractive at a willingness-to-pay threshold of$50 000/QALY gained was 56.3% (Figure 1B). For asymp-tomatic patients, CAS was associated with a 0.002 QALYbenefit and an incremental cost of $609, yielding an estimatedICER of $277,249/QALY gained with CAS versus CEA. Theprobability that CAS would be economically attractive at awillingness-to-pay threshold of $50 000/QALY gained was48.6% (Figure C). Analyses restricted to shorter time hori-zons demonstrated similar findings although the results weresomewhat more robust. For example, over a 5-year timehorizon, the probability that CEA would be economicallyattractive at a $50 000/QALY threshold was 71.3%.

DiscussionAlthough several previous studies have compared CAS ver-sus CEA for patients with carotid artery disease at standardsurgical risk,24,25 CREST is the first trial to incorporate acomprehensive health economic evaluation. In this study, wecollected detailed medical resource use and quality-of-lifedata on the complete trial population and hospital billing dataon a large subset. Results from analysis of these data revealedthat both initial treatment costs and total 1-year costs wereslightly higher for CAS versus CEA, driven largely by higher

Table 4. Utility Weights and Quality-Adjusted Life-Years Over the First Year of Follow-Up

Time PointCAS

(n�1213)CEA

(n�1193)Mean difference

(95% CI)P

Value

Baseline utility 0.697�0.130 0.702�0.126 �0.005 (�0.015 to 0.005) 0.347

2-wk utility 0.710�0.129 0.695�0.120 0.015 (0.005–0.025) 0.004

1-mo utility 0.716�0.312 0.699�0.120 0.017 (0.006–0.027) 0.001

1-y utility 0.717�0.123 0.720�0.123 �0.003 (�0.013 to 0.007) 0.579

QALYs at 1 y 0.704�0.142 0.708�0.125 �0.005 (�0.015 to 0.006) 0.403

CEA indicates carotid endarterectomy; CAS, carotid artery stenting; QALYs, quality-adjusted life-years.

Table 5. Projected 10-Y Costs, Quality-Adjusted Life-Years, and Cost-Effectiveness Ratios Based on the Markov Model

Population Cost QALYs�

Cost�

QALYsICER

(CAS versus CEA)CEA

Dominant*CEA

Preferred†CAS

Dominant*CAS

Preferred†

Overall

CAS $80 141 4.841 $524 �0.008 CEA 38.6% 54.9% 16.5% 45.1%

CEA $79 617 4.849 . . . . . . Dominant

ASX

CAS $80 314 4.862 $609 0.002 $277 249/QALY 37.3% 54.3% 17.0% 45.7%

CEA $79 705 4.859 . . . . . . Gained

SX

CAS $79 988 4.823 $448 �0.017 CEA 40.4% 56.8% 15.1% 43.2%

CEA $79 540 4.840 . . . . . . Dominant

QALYs indicates quality-adjusted life-years; �, difference between CAS and CEA strategies; ICER, incremental cost-effectiveness radio; CAS, carotid stenting; CEA,carotid endarterectomy; ASX, asymptomatic; SX, symptomatic.

*Associated with both lower cost and greater effectiveness.†Economically preferred at a societal willingness-to-pay threshold of $50 000/QALY gained.



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initial procedural costs. Results from the analysis of quality-of-life26 and health state use data tended to favor CAS duringthe first month of follow-up but revealed no differencesthereafter. Based on these findings, formal cost-effectivenessanalysis demonstrated that any projected cost and QALYdifferences between CAS and CEA were small (�0.02QALYs and �$650), such that the resulting ICERs wereunstable with approximately 50% probability of economi-cally attractive results (ie, ICER �$50 000/QALY gained)with either treatment. Similar results were observed when theanalysis was restricted to symptomatic or asymptomaticpatients. These findings suggest that for patients similar to

those enrolled in the CREST trial, there is little reason tostrongly prefer either CAS or CEA on economic grounds andthat other factors such as individual patient preferences andcenter-specific outcomes should be considered when choos-ing between these 2 approaches to carotid revascularization.

Comparison With Previous StudiesSeveral previous studies have compared initial treatmentcosts for CAS versus CEA.27–31 These studies have consis-tently shown that procedural costs are higher with CAS thanwith CEA, due almost entirely to the cost of disposabledevices (eg, stents, embolic protection devices, etc). In a

Figure. A, Scatterplot of the joint distribution of cost and QALY differences between CAS and CEA for a CREST-like population (meanage, 69 years; 53% symptomatic) based on probabilistic sensitivity analysis (1000 replications). The probability that the cost and QALYdifference is in each of the 4 quadrants is indicated. The diagonal line through the origin represents a cost-effectiveness threshold of$50 000/QALY gained. Each point below and to the right of this line represents an estimate derived from one model-based simulationfor which CAS was found to have an estimated cost-effectiveness ratio less than the threshold ratio of $50 000 per QALY gained;points above and to the left of the line correspond to model based estimates in which the incremental cost-effectiveness ratio for CASrelative to CEA was �$50 000/QALY. The probability that CEA was economically attractive at this threshold was 54.4%. Points fallingwithin the upper left-hand quadrant correspond to model-based results for which CAS was found to be dominated by CEA associatedwith both increased costs and lower effectiveness. Points falling within the lower right-hand quadrant correspond to results for whichCAS was found to be a dominant therapeutic approach associated with both lower costs and increased effectiveness in terms ofQALYs gained. The ellipse indicates the 95% credible interval for the joint distribution. B, Scatterplot of the joint distribution of costand QALY differences between CAS and CEA for a 100% asymptomatic population based on probabilistic sensitivity analysis (1000replications). The probability that the cost and QALY difference is in each of the 4 quadrants is indicated. The probability that CEA waseconomically attractive at this threshold was 51.4%. C, Scatterplot of the joint distribution of cost and QALY differences between CASand CEA for a 100% symptomatic population based on probabilistic sensitivity analysis (1000 replications). The probability that the costand QALY difference is in each of the 4 quadrants is indicated. The probability that CEA was economically attractive at this thresholdwas 56.3%. CEA indicates carotid endarterectomy; CAS, carotid artery stenting; QALY, quality-adjusted life-year.



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single-center randomized trial of 104 patients, Brooks andcolleagues27 found that variable costs were approximately$600/patient higher with CAS. Similar to our results, theyobserved modest cost savings for postprocedural care thatwere insufficient to offset the substantial increase in proce-dural costs with CAS. In a single-center observational studyof 62 patients, Pawaskar and colleagues31 found that proce-dural costs were nearly $5000/patient greater with CAS thanCEA with only minimal reductions in other hospital costs; asa result, the cost of CAS exceeded that of CEA by �$4000/patient. Using data from their hospital’s cost accountingsystem, Sternberg and colleagues32 also reported hospitalcosts that were �$3000/patient higher with CEA than CAS.On the other hand, several other single-center studies havedemonstrated substantial reductions in lengths of stay withCAS with either similar28 or lower total hospital costs.29

It is difficult to reconcile the differences between theresults of previous single-center cost studies and those of theCREST trial. The single-center studies are limited by rela-tively small sample sizes (generally �200 patients), lack ofrandomization, and limited description of costing methodol-ogy. In contrast, CREST included 2502 patients randomizedat 117 sites and incorporated costing methods based onmeasured resource use. The CREST costing methodologywas similar to that used in a variety of other cardiovasculartrials33–35 and accounted for the full costs of treatment(including allocated hospital overhead). Current guidelinesgenerally favor this approach for informing decisions regard-ing societal resource allocation, because all costs are variablein the long run.36 On the other hand, studies based onhospitals’ internal accounting systems tend to focus onvariable costs, which are more appropriate for short-termresource allocation decisions at the hospital level.

In the only other multicenter study to date, McDonald andcolleagues17 used data from the National Inpatient Sample toestimate hospital costs for nearly 200 000 patients whounderwent either CAS or CEA between 2001 and 2008. Theyfound that hospital costs were nearly $5000/patient higherwith CAS than CEA in this unselected population, a differ-ence that was explained at least in part by much higher ratesof comorbidities and complications among patients treatedwith CAS. In addition, they estimated patient-level costsbased on whole hospital cost to charge ratios. This approachhas been shown to be less precise than our approach incor-porating both resource-based costs (for procedures) anddepartment-specific cost to charge ratios (for nonproceduralcare), particularly when the admission involves a high costprocedure. Finally, their study did not consider physiciancosts, which are substantially higher with CEA (due toanesthesiology services).

Comparison With Other PopulationsSeveral previous studies have examined the relative cost-effectiveness of CAS versus CEA for patients at high risk ofsurgical complications. Maud and colleagues37 used pub-lished, aggregate data from the SAPPHIRE trial to estimatethe cost-effectiveness of CAS versus CEA for high-risksurgical patients. Over a 1-year follow-up period, they esti-mated that the ICER for CAS versus CEA was approximately

$67 000/QALY gained. Mahoney and colleagues,13 usingprospectively collected patient-level resource use from theSAPPHIRE trial, reported somewhat different findings. Al-though procedural costs were substantially higher with CASthan with CEA, there were substantial reductions in otherhospital costs such that total costs for the index hospitaliza-tion were only $500/patient higher with CAS. Lifetimeprojections of cost and life expectancy suggested that CASwas an economically attractive strategy for high-risk patientswith a lifetime ICER of approximately $6500/QALY gainedcompared with CEA.

The results of the CREST economic analysis differ fromthose from the SAPPHIRE trial because of differences inthe patient populations as well as clinical outcomes. InSAPPHIRE, patients were required to be at high risk ofcomplications from CEA because of either anatomic chal-lenges or extensive comorbidity. In that population, CASresulted in substantial reductions in hospital length of stay aswell as better clinical outcomes at 1 year, including reducedlong-term mortality.14 Consequently, despite its higher cost,CAS was an economically attractive strategy for the high-riskpopulation. In contrast, CREST enrolled a much lower-riskpatient population and demonstrated relatively small differ-ences between treatment groups in clinical outcomes and nolong-term differences in survival or quality of life. With onlyminimal differences in both long-term cost and quality-adjusted life expectancy, it is not surprising that neither CASnor CEA was clearly preferred on economic grounds. Therelative cost-effectiveness of these alternative procedurestherefore appears to depend heavily on patient characteristicsand, in particular, the likelihood of ischemic complications(death, stroke, or MI) with the 2 procedures.

Study LimitationsOur study should be considered in light of the followinglimitations. First, our analysis was performed from theperspective of the US healthcare system and may not reflectthe perspective of any other health system or payor whosecosts may differ from those we observed. In addition, thecosts we applied to resource use for our analysis includedboth fixed and variable costs. Although there is generalagreement that this approach is appropriate when consideringa long-term decision (because virtually all costs are variablein the long run), for short-term resource allocation, variablecosts may be a closer representation of the true opportunitycosts of each treatment strategy.36 Because disposable costs(which are variable even in the short term) represent a largerproportion of costs for the CAS group, restriction of ouranalysis to variable costs (which would have required accessto each hospital’s internal accounting data) would likely haveresulted in a greater cost difference between the 2 groups infavor of CEA.

Third, although CREST enrolled patients at �100 centers,the sites and operators were chosen on the basis of adequatevolumes and outcomes (for CEA) as well as an extensivetraining and certification process (for CAS). Thus, it isuncertain whether the clinical results (and by extension, theeconomic outcomes) obtained in this trial would be represen-tative of those in routine clinical practice. A recent study of



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carotid stenting in Medicare recipients revealed significantlyhigher mortality rates than those seen in CREST.38

Finally, it is important to recognize that by design, theCREST trial and its economic analysis only compared 2alternative revascularization procedures and did not include aparallel medical therapy group. Implicit in this analyticapproach is an assumption that CEA is cost-effective relativeto medical therapy for the CREST population. Althoughprevious studies support the validity of this assumption forboth symptomatic and asymptomatic patients,39 there contin-ues to be substantial debate on this issue, particularly forasymptomatic patients.40 Only a dedicated clinical trial usingboth contemporary revascularization techniques and medicaltherapy can resolve this issue.

ConclusionsIn a population of patients with carotid artery stenosis whowere not at increased risk for surgical complications, CEAwas associated with a slightly lower cost and slightly greaterquality-adjusted life expectancy compared with CAS, butcost-effectiveness results were highly unstable. These find-ings, which were derived from a controlled clinical trial withcareful credentialing of both surgeons and interventionalists,suggest that there is insufficient evidence at present tostrongly favor one or the other treatment strategy on eco-nomic grounds.

Sources of FundingSupported by the National Institute of Neurological Disorders andStroke and the National Institutes of Health (R01 NS 038384) withsupplemental funding from Abbott Vascular, Inc.

DisclosuresE. Magnuson received research grants from Eli Lilly, DaiichiSankyo, Sanofi-Aventis, and Bristol-Myers Squibb. Dr Cohen re-ceived research grants from Boston Scientific, Medtronic, AbbottVascular, and Edwards Lifesciences and consulting fees fromMedtronic, Cordis, and Abbott Vascular.

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14. Yadav JS, Wholey MH, Kuntz RE, Fayad P, Katzen BT, Mishkel GJ, etal. Protected carotid-artery stenting versus endarterectomy in high-riskpatients. N Engl J Med. 2004;351:1493–1501.

15. Brott TG, Hobson RW II, Howard G, Roubin GS, Clark WM, Brooks W,et al. Stenting versus endarterectomy for treatment of carotid-artery ste-nosis. N Engl J Med. 2010;363:11–23.

16. Sheffet AJ, Roubin G, Howard G, Howard V, Moore W, Meschia JF, etal. Design of the Carotid Revascularization Endarterectomy vs StentingTrial (CREST). Int J Stroke. 5:40–46.

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25. Ringleb PA, Allenberg J, Bruckmann H, Eckstein HH, Fraedrich G,Hartmann M, et al. 30 day results from the SPACE trial of stent-protectedangioplasty versus carotid endarterectomy in symptomatic patients: arandomised non-inferiority trial. Lancet. 2006;368:1239–1247.

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31. Pawaskar M, Satiani B, Balkrishnan R, Starr JE. Economic evaluation ofcarotid artery stenting versus carotid endarterectomy for the treatment ofcarotid artery stenosis. J Am Coll Surg. 2007;205:413–419.

32. Sternbergh WC, Crenshaw GD, Bazan HA. Carotid endarterectomy ismore cost-effective than carotid artery stenting. J Vasc Surg. 2012;55:1623–1628.

33. Bakhai A, Stone GW, Grines CL, Murphy SA, Githiora L, Berezin RH,et al. Cost-effectiveness of coronary stenting and abciximab for patientswith acute myocardial infarction: results from the CADILLAC (Con-trolled Abciximab and Device Investigation to Lower Late AngioplastyComplications) trial. Circulation. 2003;108:2857–2863.

34. Cohen DJ, Bakhai A, Shi C, Githiora L, Lavelle T, Berezin RH, et al. Cost-effectiveness of sirolimus-eluting stents for treatment of complex coronarystenoses: results from the SIRolImUS-eluting balloon expandable stent in thetreatment of patients with de novo native coronary artery lesions (SIRIUS)trial. Circulation. 2004;110:508–514.

35. Cohen DJ, Cosgrove RS, Berezin RH, Teirstein PS, Leon MB, KuntzRE. Cost-effectiveness of gamma radiation for treatment of in-stent

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36. Luce BR, Manning WG, Siegle JE, Lipscomb J. Estimating costs incost-effectiveness analysis. In: Gold MR, Siegel JE, Russell LB,Weinstein MC, eds. Cost-Effectiveness in Health and Medicine. NewYork, NY: Oxford University Press; 1996:176–213.

37. Maud A, Vazquez G, Nyman JA, Lakshminarayan K, Anderson DC,Qureshi AI. Cost-effectiveness analysis of protected carotid artery stentplacement versus endarterectomy in high-risk patients. J Endovasc Ther.2010;17:224–229.

38. Nallamothu BK, Gurm HS, Ting HH, Goodney PP, Rogers MA, CurtisJP, et al. Operator experience and carotid stenting outcomes in Medicarebeneficiaries. JAMA. 2011;306:1338–1343.

39. Kuntz KM, Kent KC. Is carotid endarterectomy cost-effective? An anal-ysis of symptomatic and asymptomatic patients. Circulation. 1996;94:194–198.

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Voeks, Thomas G. Brott and David J. CohenAlbert D. Sam II, W. Charles Sternbergh III, Fred A. Weaver, William A. Gray, Jenifer H.

Katherine R. Vilain, Elizabeth A. Magnuson, Haiyan Li, Wayne M. Clark, Richard J. Begg,Versus Stenting Trial (CREST)

Standard Surgical Risk: Results From the Carotid Revascularization Endarterectomy Costs and Cost-Effectiveness of Carotid Stenting Versus Endarterectomy for Patients at

Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright © 2012 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Stroke doi: 10.1161/STROKEAHA.112.661355

2012;43:2408-2416; originally published online July 19, 2012;Stroke.

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SUPPLEMENTAL MATERIAL

Overview of the State Transition Model

We developed a state-transition (Markov) model in order to project long-term outcomes

for the CREST population beyond the time-frame observed in the study. The model structure is

summarized in Figure S1. During the index procedure, patients could experience treatment

success, treatment failure, or attempted crossover to the alternative procedure. In addition to

these technical outcomes, patients were at risk for periprocedural events including MI, minor

stroke, major stroke, cranial nerve injury (CNI), and death. After the initial procedure, surviving

patients entered the Markov model in one of 4 health states: (1) Alive with No Major Adverse

Events (MAEs), (2) Alive Post-MI, (3) Alive Post-Minor Stroke, or (4) Alive Post-Major Stroke.

Patients who experienced more than one event were assigned to the “worst” health state using

the following hierarchy: major stroke> MI > minor stroke. In addition, each of these health

states was modified by the presence or absence of cranial nerve injury. In subsequent monthly

cycles, patients could experience a repeat carotid revascularization procedure (along with the

possibility of any of the events described for the index procedure), spontaneous major or minor

stroke, cardiovascular or non-cardiovascular death, or no event. The model was calibrated to our

cost study results at 1 month and 1 year to ensure internal validity (Table S1).

Data Sources and Key Assumptions Transition probabilities. Transition probabilities for procedural outcomes were estimated

for each treatment group based on CREST trial results from the per-protocol population and were

applied to each simulated patient based on the actual treatment received. Specific base case

values along with their underlying distributions and defining parameters are summarized in

Table S2. Most probabilities were assumed to follow a beta distribution. After the first month,

transition probabilities were based on the CREST results observed between 1 month and 12

months with rare exceptions, as described below.

Specifically, the transition probability relating to spontaneous (non-periprocedural) stroke

following the index procedure was estimated using 4-year follow-up data from CREST for the

combined treatment groups (annual rate of 2.2% for the Assigned Treatment Received

population). In addition, for patients not successfully treated with CEA or CAS, we used

published data on the annual spontaneous stroke rate for patients with carotid artery disease

treated medically.1, 2 Finally, since annual mortality for the CREST population was less than

age-adjusted U.S. averages, age- and gender-specific rates of cardiovascular and non-

cardiovascular mortality were applied based on U.S. population vital statistics data.3, 4 We

applied a fixed hazard ratio of 3.67 to the subsequent cardiovascular mortality rates of patients

who experienced a non-fatal MI during follow-up, based on analysis of CREST data for post-MI

patients.5 Since the CREST trial demonstrated similar hazard ratios for mortality after stroke or

MI, the hazard ratio for cardiovascular mortality patients after non-fatal stroke was assumed to

be equal to that following MI.

Costs. Costs for the index revascularization procedures and the incremental costs

associated with complications were based on linear regression analysis of the empirical in-

hospital cost data for the CREST trial (Table S2). Since follow-up cost data for the CREST trial

were limited to the direct costs of carotid revascularization procedures and endpoint-related

events, external data sources were used to provide more complete follow-up costs for each of the

modeled health states. Annual costs assigned to health states following the index procedure were

as follows: $9933 for Post-Minor Stroke or No Event;6 $13,088 for the first year following MI7

and $9933 for subsequent years following MI; and $22,307 for Post-Major Stroke.8 Costs of

acute events (incremental costs) were assumed to follow a log-normal distribution, while costs

associated with chronic health states were assumed to follow a gamma distribution.

Utility Weights. Health-related quality of life was assessed prospectively for the CREST

population using the Medical Outcome Study Short-Form 36 (SF-36) at baseline, 2 weeks, 1

month, and 1 year, as previously described.9 For the purposes of this analysis, the raw SF-36

data were converted to U.S. population utility weights based on the methods of Brazier and

colleagues.10 We then developed separate linear regression models to estimate the impact of

periprocedural events including MI, minor stroke, major stroke, and cranial nerve injury on the

1-month and 1-year utility weights. In addition to the outcomes of interest, these models also

adjusted for treatment group, baseline quality of life, sex, history of diabetes, age and

symptomatic status. Estimates of the impact of periprocedural events from the 1-month data

were used as inputs for the first year of follow-up; estimates from the 1-year data were used as

inputs for the post-1-year period. The specific utility weights for each health state and disutilities

associated with health states during the first year of follow-up and subsequent years were

assumed to follow either a beta distribution (for baseline utilities) or a gamma distribution (for

disutilities) and are summarized in Table S2.

Figure S1. Representation of the CREST decision model. M represents a Markov process with 5 health states, plus a mandatory, one-time Index Procedure state for each of the two treatments shown on the left. Cycle length is 1 month. Patients remain in their post-procedure health state until another event (e.g., a spontaneous stroke) occurs, with the probabilities of these events contingent upon the treatment option and the current health state. The branch from No MAEs represents the potential events, and other health states have branches with similar structures (not shown). Events that could occur during the index procedure are the same as those shown for the Repeat revascularization events.

CAS = carotid stenting; CEA = carotid endarterectomy; MAE = major adverse event; MI = myocardial infarction

Table S1. Model Calibration: Comparison of Model Results with Observed Trial Results for the Assigned Treatment Received Population at 1-Year CAS CEA

Model Observed* Model Observed*

30-day Outcomes

Death 0.2% 0.2% 0.2% 0.2%

Stroke 3.0% 3.0% 1.4% 1.4%

MI 1.3% 1.4% 3.0% 3.0%

1-year Outcomes

Dead 1.2% 1.2% 0.8% 0.8%

Stroke rate 6.0% 6.2% 3.1% 3.6%

Costs

Index Hosp $15,117 $15,104 $14,930 $14,881

1-Year hosp $15,995 $16,381 $15,918 $16,183

1-Year QALYs 0.68 0.7 0.68 0.71

Table S2. Markov Model Input Distributions

Mean (CI) Type Defining Parameters Reference

Patient Characteristics

Age at randomization 69.0 (67.9, 70.17) Normal µ = 69; SD = 8.9 11

Treatment Variables

Procedural mortality for either CAS or

CEA

0.009 (0.005, 0.014) Beta α = 13; β = 1489 CREST (mean of CAS and CEA)

Pr(medical failure of CAS proc) 0.070 (0.056, 0.085) Beta α = 86; β = 1144 CREST primary cost analysis

Pr(attempt CEA | medical failure of CAS) 0.804 (0.627, 0.986) Uniform low = 0.616; high = 1 CREST primary cost analysis

Pr(medical failure of CEA procedure) 0.007 (0.003, 0.013) Beta α = 9; β = 1242 CREST primary cost analysis

Pr(periprocedural stroke | CAS, sx pop) 0.053 (0.036, 0.072) Beta α = 32; β = 570 CREST primary cost analysis

Pr(periprocedural stroke | CEA, sx pop) 0.027 (0.016, 0.041) Beta α = 17; β = 608 CREST primary cost analysis

Pr(periprocedural stroke | CAS, asx pop) 0.027 (0.015, 0.042) Beta α = 14; β = 520 CREST primary cost analysis

Pr(periprocedural stroke | CEA, asx pop) 0.014 (0.006, 0.025) Beta α = 8; β = 551 CREST primary cost analysis

Pr(CNP | CAS procedure) 0.001 (0.000, 0.003) Beta α = 1; β = 1135 CREST primary cost analysis

Pr(CNP | CEA procedure) 0.049 (0.038, 0.062) Beta α = 58; β = 1126 CREST primary cost analysis

Pr(periprocedural MI | CAS) 0.010 (0.005, 0.016) Beta α = 11; β = 1125 CREST primary cost analysis

Pr(periprocedural MI | CEA) 0.023 (0.015, 0.032) Beta α = 35; β = 1149 CREST primary cost analysis

Disease Progression

Annual spontaneous stroke rate,

successfully treated pts

0.026 (0.020, 0.033) Beta α = 61; β = 2259 CREST annual rates after peri-

procedural period (mean of CAS

and CEA)

Annual spontaneous stroke rate,

unsuccessfully treated pts

0.030 (0.013, 0.053) Beta α = 8.7; β = 282.3 1, 2

Pr(stroke is minor) 0.662 (0.448, 0.839) Beta α = 14.8; β = 7.6 Expert opinion

Pr(repeat CAS | successful CAS), year 1 0.025 (0.017, 0.034) Beta α = 28; β = 1108 CREST primary analysis

Pr(repeat CEA | successful CAS), year 1 0.015 (0.009, 0.022) Beta α = 17; β = 1119 CREST primary analysis

Pr(repeat CAS | successful CEA), year 1 0.018 (0.011, 0.027) Beta α = 22; β = 1162 CREST primary analysis

Pr(repeat CEA | successful CEA), year 1 0.043 (0.032, 0.055) Beta α = 51; β = 1133 CREST primary analysis

Pr(repeat revascularization) > year 1 0 n/a CREST primary analysis

HR for mortality after MI or stroke 0.026 (0.020, 0.033) LogNormal m = 1.238; SD = 0.352 5

Distribution Description Mean (CI) Type Defining Parameters Reference

Costs of Acute Events

Cost of CEA procedure 7223 (5685, 9135) LogNormal m = 8.882; SD = 0.121 CREST microcosting

Cost of CAS procedure 7875 (7404, 8368) LogNormal m = 8.971; SD = 0.032 CREST microcosting

Additional cost of CEA for patients who received

attempted CAS first

756 (324, 1442) LogNormal m = 6.551; SD = 0.3889 CREST microcosting

Cost of CNP 100 (59, 157) LogNormal m = 4.575; SD = 0.247 CREST (regression model)

Acute cost of periprocedural minor stroke 7319 (6387, 8282) LogNormal m = 8.896; SD = 0.068 CREST (regression model)

Acute cost of periprocedural major stroke 13,055 (10,312, 16,383) LogNormal m = 9.473; SD = 0.114 CREST (regression model)

Cost of major stroke rehospitalization 18,470 (16,368, 21,110) LogNormal m = 9.820; SD = 0.065 12, 13

Cost of minor stroke rehospitalization 13,573 (11,636, 15,971) LogNormal m = 9.514; SD = 0.082 12, 13

Acute cost of periprocedural MI 5534 (4060, 7207) LogNormal m = 8.613; SD = 0.147 CREST (regression model)

Costs of Chronic Health States

Annual cost of medical care, post-major stroke 22,307 (7232, 36652) Gamma α = 7.111; l = 0.000 8

Annual cost of medical care, post-MI (year 1) 13,088 (3195, 14994) Gamma α = 7.111; l = 0.001 7

Annual cost of medical care, no MAE, post-minor

stroke states and post-MI after first year

9933 (4363, 18128) Gamma α = 8.054; l = 0.001 6

Utilities and Disutilities

Baseline utility 0.703 (0.462, 0.896) Beta α = 9.408; β = 4.032 CREST

Disutility of minor stroke, additive model (year 1) 0.016 (0.001, 0.050) Gamma α = 1.432; l = 87.156 CREST regression model

Disutility of major stroke, additive model (year 1) 0.099 (0.048, 0.179) Gamma α = 9.166; l = 92.471 CREST regression model

Disutility of major stroke, additive model(year >1) 0.062 (0.022, 0.125) Gamma α = 7.111; l = 114.180 CREST regression model

Disutility of minor stroke, additive model(year >1) 0.033 (0.012, 0.066) Gamma α = 7.111; l = 215.488 CREST regression model

Disutility toll for CEA (1 month only) 0.019 (0.013, 0.029) Gamma α = 22.032; l = 1122.914 CREST regression model

asx – asymptomatic, CAS – Carotid artery stenting, CEA – Carotid endarterectomy, CNP – Cranial Nerve Palsy, HR – Hazard Ratio, MAE – Major Adverse

Event, MI – Myocardial Infarction, sx - symptomatic

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