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Evidence-based Practice |
1 From the Departments of Radiology (J.L.B., J.A.K., M.T.B., M.E.A.P.M.A., G.S.G.) and Vascular Surgery (D.C.B.), Massachusetts General Hospital, Harvard Medical School, Zero Emerson Pl, Suite 2H, Boston, MA 02114; Department of Health Policy and Management, Harvard School of Public Health, Boston, Mass (G.S.G.); Department of Epidemiology and Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands (J.L.B., M.E.A.P.M.A.); and Dotter Interventional Institute, Portland, Ore (J.A.K.). Received October 15, 2001; revision requested December 26; revision received January 29, 2002; accepted April 2. Supported in part by the U.S. Department of the Army under DAMD 17-99-2-9001. Address correspondence to J.L.B. (e-mail: johanna@the-data-group.org).
| ABSTRACT |
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MATERIALS AND METHODS: A Markov decision model was developed to evaluate quality-adjusted life-years (QALYs) and lifetime costs of endovascular and open surgical repair. The incremental cost-effectiveness ratio (CER) was calculated for endovascular repair relative to open surgery in a cohort of 70-year-old men with an AAA between 5 and 6 cm in diameter. Clinically effectiveness data were derived from the literature. Cost data were derived from Medicare reimbursement rates, the hospital database, and the literature. One- and multiple-way sensitivity analyses were performed on uncertain model parameters. Costs were converted to year 2000 U.S. dollars; future costs and outcomes were discounted at 3%.
RESULTS: The incremental CER of endovascular repair was $9,905 per QALY. QALYs and lifetime costs were higher for endovascular repair than for open surgery (6.74 vs 6.52 and $39,785 vs $37,606, respectively). In sensitivity analyses, the incremental CER was insensitive to immediate conversion rate and procedure mortality rate. The incremental CER was sensitive (ie, more than $75,000 per QALY or endovascular repair was ruled out by dominance) to systemic-remote complications, long-term failures, and ruptures.
CONCLUSION: The results suggest that endovascular repair is a cost-effective alternative compared with open surgery for the elective repair of AAA. The benefits and cost-effectiveness are highly dependent on uncertain outcomes, however, particularly long-term failure and rupture rates.
Index terms: Aneurysm, abdominal, 981.73 Aorta, grafts and prostheses, 981.1286 Aorta, interventional procedures, 981.1286 Cost-effectiveness Economics, medical
| INTRODUCTION |
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In the past decade, a less invasive technology, endovascular repair, has become available for the elective repair of AAAs (9). The initial results of endovascular repair were very promising, showing a reduction in hospital stay, less blood loss, and lower complication and mortality rates compared with those of the traditionally performed open surgical procedure (10,11). At the same time, however, some limitations of the technique were reported, such as endoleaks, graft thrombosis, graft migration, or graft kinking (12). In addition, more recently, long-term results have become available that demonstrate that secondary vascular procedures are often needed and that rupture may occur (1316).
Concerns have arisen about the relative benefits and the cost-effectiveness of theendovascular technique compared with those of the open surgical procedure for the elective repair of AAAs. The value of the endovascular technique depend not only on the short-term results but also on the costs of future diagnostic imaging and subsequent treatment, the risk of rupture, and the associated health-related quality of life. From a health care policy perspective, all these aspects should be taken into account in the evaluation of the new technique. In the present study, we evaluated the cost-effectiveness of elective endovascular and open surgical repair of infrarenal AAAs by taking into account short- and long-term outcomes (17).
| MATERIALS AND METHODS |
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To model the long-term health benefits and costs, we used a Markov cycle tree (18), which updated monthly the patients clinical status and costs. With the model, QALYs and lifetime costs were estimated for each treatment strategy. Incremental CERs were calculated by dividing additional costs by QALYs gained. If one of the treatment strategies was equally or less clinically effective and more costly, the incremental CER was not calculated because we considered this treatment strategy to be ruled out by dominance (ie, the other strategy was more clinically effective and cheaper). The analysis was performed as a first-order Monte Carlo simulation (19) on the basis of the recommendations from the U.S. Panel on Cost-effectiveness in Health and Medicine (2022). Both costs and clinical effectiveness were discounted at 3% per year, and the analysis was performed from the societal perspective. All analyses were performed with software (DATA, version 3.5; TreeAge Software, Boston, Mass; Excel 97, Microsoft, Redmond, Wash).
Data Sources and Assumptions
Clinical effectiveness.The clinical effectiveness data for the model were derived from published literature, with an emphasis on studies with large patient series and cases of both (matched) endovascular and surgical repair. Our hospital database (Transition Systems, a subsidiary of Eclypsis Systems, Delray Beach, Fla) was used for additional information such as length of stays and intensive care unit admission. Approval was obtained from our hospital institutional review board to review this patient database; informed consent was not required.
In the absence of randomized clinical trials, we performed a meta-analysis of short-term results of studies to compare patients who underwent endovascular repair with (matched) patients who underwent open surgery (23). The meta-analysis included nine studies (687 endovascular procedures and 631 open surgical procedures) published in 1998 or later (2432). These studies met the following inclusion criteria: (a) Results in the study patients undergoing elective endovascular repair were compared with those in patients undergoing elective open surgical repair, (b) each treatment group included at least 10 patients, and (c) patient characteristics, complications, and mortality were reported for both groups (23). Data were independently abstracted by two reviewers (J.L.B., M.E.A.P.M.A.), and discrepancies were resolved with consensus. In the meta-analysis, we tested for heterogeneity in patient characteristics and short-term results, and the data were combined by using random-effects models, which take into account the between-study variance and the within-study variance (33).
Tables 1 and 2 show the parameter estimates for the base-case analysis and the ranges used in sensitivity analysis.
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Long-term results.In the base-case analysis, we used an average annual rupture rate (14,15). In addition, we estimated the annual risk for additional procedures performed in follow-up, excluding rupture repair, and stratified them as late conversions and percutaneous treatments (14). Long-term life expectancy was calculated on the basis of age- and sex-specific mortality rates from standard U.S. life tables of the general population. For patients with major systemic-remote complications, survival was adjusted with an excess mortality rate (35,43,44).
Health-related quality of life.Most patients with AAA who are treated electively are asymptomatic before treatment. Therefore, in our base-case analysis, quality-of-life weights before treatment were set to be similar to those in the general population (45). Furthermore, after aneurysms were treated successfully, the quality-of-life weights after recovery from treatment were similar to those before treatment (46,47) and were the same after a successful endovascular repair or open surgery (4850).
Short-term quality-of-life adjustments for patients undergoing endovascular repair or open surgery were approximated by reducing a persons quality of life by 10% for the first month after the endovascular procedure and by 30% for 2 months after the open surgical procedure. In addition, an extra toll of 3 days was subtracted for those patients who had a systemic-remote complication.
Long-term quality-of-life adjustments for patients with cardiac, cerebral, renal, or pulmonary complications were made by multiplying each year of life, adjusted for age- and sex-specific values in the general population, by a coefficient that ranged from 0 to 1 (42,51,52).
Costs
Costs included those of the procedures, morbidity and mortality, and imaging in follow-up (Table 2) (3841). All costs were converted to year 2000 U.S. dollars on the basis of the Medical Component of the Consumer Price Index (53).
Procedure costs.Procedure costs included those of the hospital, physician, and patient for endovascular repair, open surgery, percutaneous treatment (eg, coil embolization), and emergent surgical repair of rupture. Both the hospital costs and physician fees were derived from Medicare reimbursement rates by using the Diagnosis Related Group, or DRG, 110 and 111 codes for hospital costs and the Current Procedural Terminology, or CPT, code for physician fees (54,55). The hospital costs for each intervention were adjusted on the basis of the corresponding coding distributions for that intervention that were derived from our hospital database.
Patient costs included time. Time costs were determined by multiplying the daily wage rate by the number of days spent in the hospital. The daily wage rate was estimated by dividing the published full-time median weekly wage rate for all men in the United States by 5 days ($129 per day) (56). The time required for treatment was based on the length of hospitalization, which was estimated from that for patients undergoing these procedure in our hospital: endovascular repair, 4 days; open surgery, 9 days; percutaneous treatment, 1 day; and emergent repair of rupture, 14 days.
Costs of morbidity and mortality.If a major systemic-remote complication occurred during the procedure, extra costs were added to the procedure costs. These additional costs were based on the number of days a patient was admitted to the intensive care unit multiplied by the cost of an intensive care unit day. The number of days a patient was admitted to the intensive care unit was determined on the basis of the number of days patients were admitted to the intensive care unit in our hospital: endovascular repair, 1 day; open surgery, 2 days; and emergent repair, 14 days. The cost of a day in the intensive care unit was determined in a previous study (57) by means of multiple regression analysis ($1,543 per day). Long-term costs of cardiac, cerebral, renal, and pulmonary complications were based on those in the literature (3841). Costs of procedure-related mortality (within 30 days after the procedure or when the aneurysm ruptured) were estimated as the cost of 5 intensive care unit days (ie, 5 x $1,543). In addition, we added the costs for associated physicians for those days (ie, $592 total).
Costs of follow-up.Costs of follow-up included hospital costs for imaging, the cost of a physician visit, and patient costs. We assumed that all patients underwent computed tomography (CT) (5860). In the model, patients underwent imaging at 3, 6, and 12 months in the first year after the endovascular procedure and annually thereafter. Patient time for imaging was estimated by multiplying the daily wage rate by 0.5 per day. Other possible future costs were assumed to be similar for endovascular repair and open surgery and were therefore not included in the model.
Sensitivity Analysis
One- and multiple-way sensitivity analyses were performed on model assumptions and uncertain model parameter estimates, such as complication and mortality rates, immediate conversion rates, health-related quality-of-life weights, and rupture and long-term failure rates. To identify the value of the variables at which the optimal treatment option changes, we performed threshold analyses. The threshold values for variables at which the preferred treatment option changes were determined with a commonly used cutoff value of an incremental CER of $75,000 per QALY (61).
In addition, uncertainty exists in hospital cost for endovascular repair compared with that for open surgery. Previously, results of cost studies demonstrated that the actual hospital costs for elective endovascular repair could be either lower or higher than those for open surgery (17,29,57,6267). In a sensitivity analysis, we replaced the Medicare hospital costs with the actual hospital costs derived from our hospital accounting database for endovascular repair, open surgery, emergent repair of a ruptured aneurysm, percutaneous treatment (based on coil embolization), and CT. It should be noted that the actual hospital costs for endovascular repair were higher than those for open elective surgery (factor of 1.05) and that the costs of emergent repair were more than twice those of open elective surgery (factor of 2.21). In additional sensitivity analyses, we increased the hospital costs for endovascular repair to the hospital costs of open surgery multiplied by a factor that ranged from 0.5 to 2.0. Furthermore, we increased the hospital costs for immediate conversion to surgery after endovascular repair to those for open surgery plus the approximate cost of a stent graft (ie, from $23,484 in the base-case analysis to $33,484).
| RESULTS |
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Long-term failure and rupture rates.In a two-way sensitivity analysis, we varied the annual rates of rupture and percutaneous or surgical procedures performed in follow-up (Fig 3). Long-term failure and rupture rates each had an effect on the incremental CER. If the annual rate for procedures performed in the follow-up was increased from 8% to 12%, with the annual rupture rate kept at the base-case value (ie, 1%), the incremental CER was increased to $56,630 per QALY (Table 4). If the annual rate for procedures in follow-up exceeded 12%, the incremental CER was more than $100,000 per QALY. If the annual rupture rate was increased from 1% to 1.6%, with the annual rate for procedures in follow-up kept at base-case level (ie, 8%), endovascular repair was dominated by open surgery (endovascular repair had equal clinical effectiveness and higher costs compared with those for open surgery) (Fig 3, Table 4).
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Additional sensitivity analyses.In additional sensitivity analyses, we varied the mortality rates of rupture and emergent repair, the complication rate of emergent repair, the quality-of-life coefficients, and the discount rate. These changes did not influence the base-case incremental CER (<$20,000 per QALY). With the annual long-term failure rate after open surgery decreased from 1% to 0.5%, the incremental CER increased to $54,233 per QALY (Table 4). With the odds ratio for excess mortality rate among the patients with systemic-remote complications decreased from 1.8 to 1.3, endovascular repair was dominated by open surgery (ie, endovascular repair was less clinically effective and had higher costs).
| DISCUSSION |
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On the basis of the best estimates for all model parameters, our results demonstrate that endovascular repair is a clinically effective and cost-effective alternative to open surgery for the elective repair of AAA. The results of our study, however, were highly sensitive to the varying of uncertain parameters in the model, such as the systemic-remote complication rate, long-term failure rate, and rupture rate. For example, if the complication rate after endovascular repair was 5% higher than the base-case estimate, endovascular repair was dominated by open surgery (ie, endovascular repair was less clinically effective and more costly). If the annual long-term failure rate after endovascular repair with treatment required was 13% or higher, the incremental CER was greater than $75,000 per QALY. Also, if the annual rupture rate after endovascular repair was greater than 1.5%, with the other parameters kept at the base-case values, endovascular repair was no longer cost-effective at the treatment threshold of $75,000 per QALY but was dominated by open surgery. Furthermore, the procedural costs of endovascular repair influenced the incremental CER. If the endovascular procedure costs were 1.5 times the costs of open surgery, the incremental CER for endovascular repair was greater than $75,000 per QALY.
The sensitivity of these results to certain model parameters is notable. Higher values have been reported in some studies for the systemic-remote complication rate after endovascular repair (eg, 18%, including cardiac, renal, cerebral, and pulmonary complications [68]) and annual rupture rate after endovascular repair (ie, 1.4% [15]). In addition, lower values have been published for a systemic-remote complication rate after open surgery (eg, 19% [16]), and results of a cost study have been published of hospital costs for endovascular repair that were 1.6 times those for open surgery (62). Because endovascular repair is a relatively new procedure, only limited long-term follow-up is available in published series. The most common long-term problem is an endoleak, a persistent filling of the aneurysm. The consequences of endoleaks, however, in terms of both their clinical outcomes and costs are still unclear and may differ for the various types of endoleaks (12,69). In addition, findings in studies with long-term results after an endovascular procedure demonstrate that rupture or secondary procedures could not be predicted on the basis of the presence or absence of an endoleak (13,14). Therefore, in our study, the clinical and cost consequences of procedures performed in follow-up were modeled independently of disease status. To decrease concerns about the clinical effectiveness and cost-effectiveness of endovascular repair, more details are needed about the severity of the complications, the number of additional percutaneous treatments required, and the number of late conversions to open surgery.
Our results expand on and confirm those of a previously published cost-effectiveness study of endovascular repair and open surgery performed by Patel et al (17). They concluded that endovascular repair was a cost-effective alternative to open surgery for the elective repair of AAA and that the incremental CER was highly sensitive to the systemic-remote complication rate. In our study, the data for short-term results were more up to date, but we also included recently published long-term reports of rupture and additional procedures performed. We found that in addition to the complication rate, the incremental CER was highly sensitive to rupture rate and the number of additional procedures performed.
Our analysis has several limitations. The parameter estimates of our model were not derived from randomized clinical trials. Because of the promising initial results of endovascular repair, randomized clinical trials were ethically hard to organize. In our study, the parameter estimates were principally based on results in several large patient series and a meta-analysis of nine studies to compare short-term results of endovascular repair and open surgery. In the meta-analysis, patients in the endovascular and open surgery groups were matched on the basis of patient and lesion characteristics in four of the nine studies (26,27,29,32). In the other studies, patients were not matched between the treatment groups, but the patient and lesion characteristics were not significantly different (24,25,28,30,31). To evaluate the relative benefits of endovascular repair and open surgery more accurately, data from randomized clinical trials are needed.
Several assumptions were required for our analysis. For example, we made assumptions about the recovery time after treatment, cost of mortality, quality of life, cost of morbidity in follow-up, excess mortality rate, and number and type of additional procedures performed. Also, we assumed that 25% of the patients with renal complications were dependent on dialysis; this percentage was probably too high after endovascular repair. By performing sensitivity analyses, however, we evaluated the influence that any uncertainty in these assumptions may have on the base-case incremental CER.
In the present study, we compared results of endovascular repair and open surgery in patients with AAA who were eligible for both procedures. In many cases, however, patients may be eligible for only one of the procedures. Patients eligible for surgery may not be eligible for endovascular repair because of specific morphologic requirements for the endovascular procedure. Also, not all patients eligible for endovascular repair are eligible for surgery because of the higher perioperative mortality risk. After future developments of the endovascular technique are taken into account, it may be that the rate of eligibility of patients with AAA for endovascular repair is higher than that for open surgery. Future development of stents, deployment techniques, and/or the procedure, such as the use of local anesthesia, may lead to endovascular repair of smaller aneurysms and thereby allow a simpler endovascular graft design (eg, tube grafts [70]). These developments may lead to a further decrease in complications after endovascular repair compared with those after open surgery and to the prevention of long-term problems (71). As soon as data become available, our model can be used to identify patient groups and treatment thresholds for which either endovascular repair, open surgery, or surveillance is the preferred treatment option.
In conclusion, our results, which are based on the best available data from a wide range of studies, suggest that endovascular repair is a cost-effective alternative compared with open surgery for the elective repair of AAA. However, the benefits and cost-effectiveness are highly dependent on uncertain outcomes, particularly systemic-remote complications and long-term failure and rupture rates.
| FOOTNOTES |
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Abbreviations: AAA = abdominal aortic aneurysm, CER = cost-effectiveness ratio, QALY = quality-adjusted life-year
Author contributions: Guarantors of integrity of entire study, J.L.B., G.S.G.; study concepts, all authors; study design, J.L.B., G.S.G.; literature research, J.L.B., M.T.B., M.E.A.P.M.; data acquisition, J.L.B.; data analysis/interpretation, J.L.B., J.A.K., D.C.B., G.S.G.; statistical analysis, J.L.B.; manuscript preparation and definition of intellectual content, J.L.B.; manuscript editing, revision/review, and final version approval, all authors.
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