PROJECTED HEALTH AND ECONOMIC BENEFITS OF THE USE OF SIROLIMUS-ELUTING CORONARY STENTS Rodolphe Ruffy, MD, FACC,* and Raymond J. Kaden, MBA, CPA ABSTRACT Despite remarkable technological progress in interventional cardiology, the success of percutaneous coronary intervention (PCI) remains limited by in-stent restenosis. Recent trials of sirolimuseluting stents have shown promising results regarding this complication. We estimated the potential health-economic benefits of sirolimuseluting stents. A decision-analytic model was developed from a payor s perspective to estimate the cost effectiveness of sirolimus-eluting stents compared with standard bare-metal stents in PCI, as well as with coronary artery bypass graft (CABG) surgery for a 500 000-member healthcare plan. The model input health plan specific data for volume and reimbursement rates for PCI and CABG; the results of a randomized trial comparing the 2 types of stents were used as a reference. A mean of 1.4 stents per patient for comparisons with PCI, and 2.8 stents per patient for comparisons with CABG in multivessel cases, and an incremental cost of $2000 per stent for the drug-eluting versus the bare-metal stent were assumed. Supposing that patients at high risk for restenosis are selected first, the use of a sirolimuseluting stent rather than a standard stent in 49% of current PCIs was associated with a total cost increase of $295 for the plan and 202 fewer hospital days. If all patients who currently receive a *Cardioscript International, Salt Lake City, Utah. Certified Public Accountant, Spring Lake, New Jersey. Address correspondence to: Rodolphe Ruffy, MD, 4228 S Park Terrace, Salt Lake City, UT 84124. E-mail: cardioscpt@aol.com. Acknowledgment: The authors acknowledge the contributions of Brian Firth, MD, PhD, and Pamela Palazola, from Cordis Corporation, for their assistance in obtaining the data needed for this analysis. standard stent received a sirolimus-eluting stent, an incremental cost of $568 823 for the health plan and 284 fewer hospital days were calculated. If all patients currently eligible to receive a standard stent, plus 39% of patients with multivessel disease who are typically referred for CABG surgery, were treated instead with a sirolimus-eluting stent, the estimated savings for the health plan totaled $2993, and hospital days were reduced by 745 days. In this model, substituting a sirolimus-eluting stent for a bare-metal stent in patients at high risk for in-stent restenosis was cost-neutral and reduced the incidence of repeated hospitalization. Sirolimus-eluting stents offer substantial cost savings for a health plan if their use can be expanded to a modest subset of patients currently referred for CABG surgery. (Adv Stud Med. 2003;3(6D):S602-S611) Coronary artery disease (CAD) is the number-one cause of death in the United States, for both men and women. Over the past few decades, several new therapies have been developed to treat this disease and to improve patient care and prevent adverse events. Coronary artery bypass grafting (CABG) is a well-established surgical treatment for severe multivessel CAD. Approximately 519 000 CABG procedures were performed in the year 2000. Due to the invasive nature of the surgery, patients are typically hospitalized for 6 to 8 days, followed by approximately 4 to 6 weeks of home convalescence. Physicians and patients have long sought less invasive alternatives to CABG. The growing use of coronary stents is one of the most striking clinical developments in the field of interventional cardiology S602 Vol. 3 (6D) June 2003
during the past decade. Commencing with the first uncontrolled reports of the value of coronary stenting after balloon angioplasty 10 to 14 years ago, 1,2 this treatment has become an integral part of most percutaneous coronary interventions (PCIs) that have been driven by the results of several major randomized, controlled, clinical trials. 3-6 However, the long-term success of these interventions remains limited by the phenomenon of in-stent restenosis. 7,8 This delayed complication of coronary stenting is caused by the accelerated in-growth of vascular wall tissue in reaction to the injury caused by dilatation of the lesion and insertion of a foreign body (ie, the stent). Restenosis, which occurs in 30% to 50% of patients within 6 months after balloon angioplasty, has been reduced to 20% to 30% by the implantation of stents, but it still remains a significant challenge. In the year 2000, approximately 900 000 PCIs were performed in the United States; stents were implanted in approximately 84% of these procedures. In a recent comparison of CABG with stenting for multivessel disease, further revascularization procedures were needed within 1 year in more than 20% of patients randomized to stenting, versus less than 5% of patients treated surgically. 6 However, CABG is not a benign procedure. Over 15% of Pennsylvania patients undergoing CABG in 1999 were readmitted for further treatment, amounting to $18 438 in additional charges for the 15% of patients that were readmitted within 30 days of having CABG surgery. 9 The systemic or local delivery of several pharmaceuticals has been generally unsuccessful at inhibiting restenosis after coronary interventions. 10 By contrast, the development of a new sirolimus-eluting stent (SES) successfully prevented the development of restenosis in an observational clinical study published in January 2001. 11 The Figure shows a representative series of angiograms from a patient included in that pilot study. The total absence of arterial narrowing at the site of stent implantation after a follow-up of 2 years is particularly noteworthy. In addition, the results of the recently reported Randomized Study with the Sirolimus-Eluting Velocity Balloon-Expandable Stent in the Treatment of Patients with De Novo Native Coronary Artery Lesions (RAVEL) trial, a randomized, double-blind, controlled trial of the SES compared with a standard bare-metal stent (SBMS), have confirmed the remarkable effectiveness in terms of preventing restenosis and the need for repeated procedures up to 1 year. 12 The purpose of the present analysis was to evaluate the potential economic consequences of the widespread use of this new SES, which is already available outside the United States, and was approved by the Food and Drug Administration in April 2003 for the treatment of patients with de novo coronary lesions. METHODS A decision-analytic model was developed from a payor s perspective to project the potential cost effectiveness of the SES compared with SBMS in PCI, and in patients currently undergoing CABG. The model allows input of health plan specific data for volume and reimbursement rates for PCI and CABG. In addition, the model calculates reimbursement costs for hospitalization by procedure and assumes an incremental reimbursement of $2800 per patient for procedures using the SES. It also uses as a reference for its Figure. Representative Angiogram of Right Coronary Artery from a Patient Included in the Pilot Study of the Sirolimus-Eluting Stent Left upper panel (Pre): presence of severe narrowing of the proximal right coronary artery (arrow); right upper panel (Post): arterial narrowing is no longer visible immediately after implantation. Lower panels (1 y and 2 y): artery has remained widely patent (arrow) at 1 and 2 years after stent implantation. Advanced Studies in Medicine S603
calculation of the clinical benefits of SES the results of a recently completed randomized trial (RAVEL) comparing SES with SBMS for the revascularization of single, de novo native coronary lesions. 12 In that trial, angiographic restenosis rates associated with the SES versus the SBMS were 0% versus 26.6%, respectively. In addition, the incidence of major adverse cardiac events, including need for further PCI up to 1 year of follow-up, was markedly lower in the group of patients treated with SES than in patients treated with SBMS. The major findings of the RAVEL trial are presented in Table 1. The model assumes a 90% relative reduction in the need for reintervention. A sensitivity analysis was also conducted using 80% and 100% relative reduction in reintervention rates. For our base-case analysis, we assumed a mean utilization of 1.4 stents per patient for comparisons with PCI in single-vessel cases, 2.8 stents per patient for comparisons with CABG in multivessel cases (based on the Arterial Revascularization Therapy Study [ARTS]), and an incremental cost of $2000 per stent for the SES versus the SBMS. The demographics for a 500 000-member health plan and major clinical and economic assumptions used to compute costs are summarized in Tables 2 and 3. Details of the financial model are presented in Table 4. MODEL CALCULATIONS The model was constructed to calculate the following variables: (1) diagnostic/interventional procedure ratio; (2) PCI/CABG ratio; (3) the estimated number of de novo PCIs within a population; and (4) the estimated number of patients undergoing a first revascularization procedure. Patients undergoing a repeated revascularization at the time of the index treatment (restenotic lesions) were not included in this analysis. SUBGROUP ANALYSES PCI Strategy. PCI treatment strategy cost savings were calculated by reducing 1 PCI readmission for each high-risk patient up to the cost-neutral or breakeven point. Surgery Strategy. Cost savings were calculated by the difference in the reimbursement cost for CABG vs PCI and SES. No other hospitalization or outpatient costs were assumed in these calculations. As such, this represents a conservative approach toward cost offsets because repeated admissions that do not result in reinterventions, diagnostic tests that may precede reintervention, and additional physician fees are not included. The model was applied with the assumption that the SES is the treatment alternative in 3 separate scenarios: (1)High-risk indications: Assuming that patients at high risk of restenosis are selected first, this model calculated the percentage of patients who should receive an SES instead of an SBMS to result in a net break-even economic outcome for the healthcare plan at 1 year; (2) All standard indications: This second model calculated the economic outcome at 1 year if all patients who at present typically receive SBMS received an SES; (3) Expanded indications: The third model cal- Table 1. Incidence of In-Stent Restenosis at 6 Months, and MACE up to 1 Year of Follow-up in the RAVEL Study* Sirolimus-Eluting Bare-Metal Stent (n = 120) Stent (n = 118) Restenosis at 6 months (% of patients) 0 26.6 MACE In-hospital Death 0 0 MI 3 3 CABG 0 0 Between discharge and 1year Death 2 2 MI 1 2 CABG 1 1 PCI (%) 0 27 Overall MACE: 0-1 year, n (%) 7 (5.8) 34 (28.8) Cumulative event-free survival (%) 94.1 70.9 *Unless otherwise indicated, values indicate numbers of patients. When more than 1 MACE occurred in same patient, the most severe is counted. P <.001. MACE = major adverse cardiac events; RAVEL = Randomized Study with the Sirolimus-Eluting Velocity Balloon-Expandable Stent in the Treatment of Patients with De Novo Native Coronary Artery Lesions; MI = myocardial infarction; CABG = coronary artery bypass graft; PCI = percutaneous coronary intervention. Morice et al. N Engl J Med. 2002;346(23);1778. 12 2002 Massachusetts Medical Society. All rights reserved. Adapted (translated) with permission 2003. S604 Vol. 3 (6D) June 2003
culated the economic outcomes if all patients who at present receive SBMS are included, and the percentage of patients who at present are typically referred for CABG that are necessary to result in a net break-even economic outcome for the health plan at 1 year. RESULTS The risk stratification scheme, with estimated probabilities of reintervention based on lesion angiographic characteristics in diabetic versus nondiabetic patients, is presented in Table 5. This scheme was developed from a large clinical database of patients who underwent PCI in several multicenter randomized stent trials. 13 The results shown here assume a 90% reduction in the 7 categories of reintervention rates that were derived from Table 5, as outlined in Tables 5a and 5b, for both the diabetic and nondiabetic populations. Patients were brought into the model at 90% relative reduction in target-lesion revascularization of those rates outlined in Tables 5a and 5b, when treated with the SES. This was based on the results of the RAVEL clinical trial, which reported 0% target-lesion revascularization rate for patients treated with the SES. The percentage of patients treated with the SES in each category is also outlined in Tables 5a and 5b, line 3. Table 6 presents the results of the model in standard high-risk indications with single-vessel treatment. It was estimated that the use of the SES instead of the SBMS in 49% of procedures (490 patients) would be associated with a total cost increase of $295 and 202 fewer days of hospitalization (economic break-even for the health plan). The 49% of patients treated were from the high-risk diabetic and nondiabetic groups and adjusted baseline risk of reintervention rates were calculated at 27.1% and 20.4%, respectively, as noted in Tables 5a and 5b. Table 7 presents the results of the model if all patients who are currently eligible for the implantation of SBMS with single-vessel interventions were treated with the SES. Because the model excludes repeated procedures and retains de novo lesions only, 100% of the eligible population would include 1001 patients. The inclusion of the subgroup of patients at lower risk of reintervention was associated with an incremental cost of $568 823 for the health plan, and 284 fewer days of hospitalization. The Table 2. Health Plan Demographic Characteristics 500 000-member health plan Number of diagnostic catheterizations 4000 Number of angioplasties without stent implantation 368 Number of angioplasties with stent implantation 1472 Total number of angioplasties 1840 Number of CABG operations 1000 Average reimbursement for CABG surgery Single-vessel disease $22 000 Multivessel disease $24 000 CABG = coronary artery bypass graft. Table 3. Major Economic Model Assumptions for a Study Period of 12 Months Bare-metal stent Reintervention rate Clinical Outlined in Tables 5a & 5b SES Reduction in reintervention 80%, 90%, 100% Diabetics (% of population) 30% Estimated mean number of stents implanted Standard indication (single-vessel treatment) 1.4 Expanded indication (multivessel treatment) 2.8 Economic Mean length of hospitalization for PCI 2.3 days Mean length of hospitalization for CABG 8.3 days Per-stent incremental reimbursement for SES $2000 SES = sirolimus-eluting stent; PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft. Advanced Studies in Medicine S605
adjusted baseline risk of reintervention rates were calculated at 19.3% for diabetic patients and 13.8% for nondiabetic patients, as noted in Tables 5a and 5b. Finally, Table 8 presents the results of the model where all patients currently eligible to receive SBMS receive a SES, plus 39% of patients with multivessel CAD who are typically referred for CABG procedures are treated with the SES. Use of the SES instead of surgery in this subpopulation alone would save the health plan $571 817 and eliminate 745 postoperative hospital days, resulting in an overall saving of $2993 for the combined treatment strategy (a break-even scenario). Because the CABG population treated in the United States currently includes approximately 10% of patients with single lesions and 25% of patients with lesions in 2 vessels, this scenario is realistic. Results of the sensitivity analysis using 80%, 90%, and 100% relative rates of reduction of reintervention are also shown. As the relative rate of reduction of reintervention increases, so does the percentage of patients who can be treated with the SES up to the cost-neutral point before considering any shift from CABG. For the shift from SBMS to the SES, the cost-neutral points are as follows: 34% at an 80% relative reduction, 49% at a 90% relative reduction, and 62% at a 100% relative reduction in reintervention versus SBMS. The costs for treating the entire population who are eligible for stents with an SES thus decreases as the relative reduction in reintervention increases. The percentage of patients shifting from CABG to arrive at a cost-neutral point also decreases as the relative reduction in reintervention with the SES increases. DISCUSSION In 1994 a new era in PCI treatment was introduced in the United States. In the year 2000, approximately 900 000 PCIs were performed in the United States, and stents were implanted in 84% of these procedures. Despite various approaches to prevent its development, clinically significant restenosis continues to occur in 20% to 30% of patients after stent implantation, resulting in additional hospitalizations and interventions in Table 4. SES Financial Model Indication PCI Surgery Economic assumptions Cost per SES (US $)* 3200 3200 Cost per bare-metal stent (US $) 1200 1200 Procedure cost multiplier (% change from initial to first repeat PCI) 1 1 Reimbursement for CABG (US $) Single-vessel Multivessel 22 000 24 000 Reimbursement for angioplasty without stent implantation (US $) 9000 - Clinical assumptions Percentage diabetics (stent procedures) 30 - Number of stents per procedure 1.4 2.8 Mean duration of hospitalization (days) 2.3 8.3 Study period (months) 12 12 Baseline % clinical restenosis (all patients) 20 40 Percentage clinical restenosis (SES, all patients) 4, 2, 0 8, 4,0 Percentage reduction in reintervention (CYPHER) 80, 90, 100 80, 90, 100 *Based on amount charged during clinical trials. US price had not been established at the time of this article. SES = sirolimus-eluting stent; PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft. Table 5. Risk Stratification Scheme Showing Probabilities of Need for Reintervention Based on Lesion Angiographic Characteristics in Diabetic and Nondiabetic Patients Diabetics vs Nondiabetics Risk of Restenosis Lesion length (mm) Reference vessel diameter (mm) 10 20 30 Risk Level Diabetics 2.5 23% 29% 33% 3.0 15% 20% 24% High 3.5 10% 13% 17% Intermediate 4.0 6% 8% 11% Low Nondiabetics 2.5 18% 22% 27% 3.0 11% 15% 19% High 3.5 7% 9% 12% Intermediate 4.0 4% 5% 8% Low Data from Ho et al. 13 S606 Vol. 3 (6D) June 2003
15% to 20% of patients. In addition, approximately 519 000 CABG operations were performed in the same year. ECONOMIC IMPLICATIONS FOR THE HEALTHCARE SYSTEM It is estimated that reinterventions currently affect 150 000 to 200 000 patients annually in the United States, at a cost to the healthcare system of about $1.5 to $2 billion in revascularization procedures. Sirolimuseluting stents have the potential to decrease the restenosis rate by 90% to 95% and the need for reintervention by 80% to 100%, depending on the severity of the disease, thereby reducing the costs associated with repeated revascularization. They will clearly cost more than SBMS at the time of the index procedure. These devices are much more complex to manufacture than bare-metal stents because they include 3 components: the stent; the appropriate polymers that are modified to release the drug over a 30- to 45-day period; and the drug sirolimus. However, the potential reduction in reinterventions has important implications for reducing the direct medical costs associated with repeated PCI. These reinterventions typically occur in the first 4 to 8 months after the index procedure so that the cost Table 5A. SES* Diabetic Calculations Extrapolated* Low Risk Avg of Adjacent Med Risk Avg of Adjacent High Risk (Extrapolated)* 1. Reintervention risk 6.1% 8.8% 12.5% 16.3% 21.8% 27.3% 34.1% 2. % procedures at risk level 5.8% 11.5% 14.3% 17.0% 19.2% 21.4% 10.8% 3. % treated w/ CYPHER 100.00% 94.25% 82.75% 68.50% 51.50% 32.25% 10.75% 4. Adjusted baseline risk 19.3% 20.4% 22.1% 24.1% 26.6% 29.5% 34.1% 1) Rate of reintervention risk in each category; 2) percentage of procedures in each category; 3) cumulative percentage of patients being brought into the model; 4) the blended or adjusted rate of reintervention based on the percentage of patients being brought in to the model. SES = sirolimus-eluting stent; Avg = average; Med = medium. *Linear extrapolation beyond the data set; The average of low rates of risk of restenosis for diabetics in Table 5; Average of the low and medium risk and the medium and high risk, respectively; The average of intermediate risk of restenosis for diabetics in Table 5; The average of high risk of restenosis for diabetics in Table 5. Table 5B. SES* Nondiabetic Calculations (Extrapolated)* Low Risk Avg of Adjacent Med Risk Avg of Adjacent High Risk (Extrapolated)* 1. Reintervention risk 4.1% 6.0% 8.9% 11.8% 16.6% 21.5% 27.8% 2. % procedures at risk level 6.8% 13.4% 15.8% 18.0% 18.2% 18.5% 9.3% 3. % treated w/ CYPHER 100.00% 93% 80% 64% 46% 28% 9.3% 4. Adjusted baseline risk 13.8% 14.9% 16.4% 18.3% 20.8% 23.6% 27.8% 1) Rate of reintervention risk in each category; 2) percentage of procedures in each category; 3) cumulative percentage of patients being brought into the model; 4) the blended or adjusted rate of reintervention based on the percentage of patients being brought in to the model. SES = sirolimus-eluting stent; Avg = average; Med = medium. *Linear extrapolation beyond the data set; The average of low rates of risk of restenosis for diabetics in Table 5; Average of the low and medium risk and the medium and high risk, respectively; The average of intermediate risk of restenosis for diabetics in Table 5; The average of high risk of restenosis for diabetics in Table 5. Advanced Studies in Medicine S607
savings are realized within the first year of treatment. These cost savings to payors are illustrated in Tables 6 and 7 for 2 different scenarios: one in which only patients at the highest risk of reintervention are treated with the SES, and the other in which all patients currently treated with an SBMS receive an SES. It is important to note that these models only reflect the third-party payor cost (reimbursement) savings, and do not reflect the overall societal benefits expected from this new technology in terms of potential reduction in costs borne by the patient, such as transportation, lodging, or the need for assistance in their daily life activities. Nor does it include costs to employers, such as absence from work or reduced productivity. The third scenario considers the potential outcome for a payor if all patients who are currently treated with an SBMS receive an SES and an additional 39% of patients currently undergoing CABG procedures are treated with the SES. It is clear that even a relatively modest shift of patients from CABG to the SES would result in a break-even economic outcome or in cost savings for the health plan, even if patients Table 6. Model Outcomes for High-risk Standard Indications Among Total Pool of 1001 Patients Eligible for First PCI in 500 000-Member Healthcare Plan Percent relative reduction in reintervention 80 90 100 Percent of procedures using SES instead of bare-metal stents at neutral cost 34 49 62 Adjusted baseline rate of reintervention of population Diabetic 29.3 27.1 24.8 Nondiabetic 22.7 20.4 18.3 Number of patients receiving SES instead of bare-metal stents 340 490 621 Number of hospital days eliminated 137 202 260 Total cost increase (savings US $) 244 295 (401) PCI = percutaneous coronary intervention; SES = sirolimus-eluting stent. Table 7. Model Outcomes for All Standard Indications in 1001 Patients Eligible for First PCI in 500 000-Member Healthcare Plan Percent of relative reduction in reintervention 80 90 100 Percent of procedures using SES instead of bare metal stents 100 100 100 Number of patients receiving SES instead of bare-metal stents 1001 1001 1001 Number of hospital days eliminated 252 284 316 Total cost increase (US $) 692 415 568 823 446 718 PCI = percutaneous coronary intervention; SES = sirolimus-eluting stent. Table 8. Model Outcomes in All Patients with Standard Indications for Stent Implantation Plus Subgroup of Patients Currently Referred for Coronary Artery Bypass Graft Surgery in 500 000-Member Healthcare Plan Percentage relative reduction 80 90 100 in reintervention PCI CABG PCI CABG PCI CABG Percent of procedures using SES instead: 100 58 100 39 100 26 of bare-metal stents (PCI) or surgery (CABG) Number of patients receiving SES instead: 1001 185 1001 124 1001 83 of bare-metal stents (PCI) or surgery (CABG) Number of hospital days eliminated 252 1108 284 745 316 497 Total cost increase (US $) 692 415 568 823 446 718 Total cost savings (US $) 693 571 571 817 451 511 Net savings (US $) 1156 2993 4793 PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft; SES = sirolimus-eluting stent. S608 Vol. 3 (6D) June 2003
currently treated with SBMS were exclusively treated with an SES. The impact on decreasing hospital costs and length of convalescence, not to mention the impact on quality of life as a result of these benefits to patients, is particularly striking in this scenario. CONCLUSIONS Despite remarkable advances in percutaneous techniques of coronary revascularization and adjunctive pharmacologic interventions, in-stent restenosis remains a clinical challenge and an economic burden on the healthcare system. Sirolimus-eluting stents represent a promising cost-effective solution to this persistent complication. QUESTIONS AND ANSWERS In this question-and-answer section, Rodolphe Ruffy, MD, FACC, and Raymond J. Kaden, MBA, CPA, respond to questions posed by Earl P. Steinberg, MD, MPP, featured in the CLINICIAN INTERVIEW section on page 612. RESTENOSIS RATE IN PATIENTS WITH VARYING LEVELS OF RISK OF RESTENOSIS AND PREVALENCE OF PATIENTS IN DIFFERENT RISK CATEGORIES Dr Steinberg: The analysis assumes that the benefits of drug-eluting stents are the same in high-risk and lower-risk patients. While available data have shown benefits in both types of patients, there is not enough data available for high-risk patients to know with confidence what the restenosis rate really is. Was this uncertainty addressed in a sensitivity analysis? Dr Ruffy: Seven categories of restenosis rates were derived from Table 5 as outlined in Tables 5A and 5B (page 607), for both the diabetic and nondiabetic populations. The categories were developed by averaging the low, intermediate, and high risks of restenosis from Table 5 and identifying the averages between low and intermediate risk, between intermediate and high risk, and extrapolating a category on the low end and high end for both populations. Patients were brought into the model at 90% relative reduction in target-lesion revascularization of those rates outlined in Tables 5A and 5B when treated with the sirolimus eluting stent (SES), based on the results of the Randomized Study with the Sirolimus- Eluting Velocity Balloon-Expandable Stent in the Treatment of Patients with De Novo Native Coronary Artery Lesions (RAVEL) trial, which reported 0% restenosis rate for patients treated with the SES. The percentage of patients treated with SES in each category is also outlined in Tables 5A and 5B, line 3 (page 607). SENSITIVITY ANALYSIS A sensitivity analysis was conducted using 80%, 90%, and 100% relative rates of reduction in reintervention and results were included in Tables 6, 7, and 8. As the relative rate of reduction of reintervention increases, so does the percentage of patients that can be treated up to the cost-neutral point. The cost-neutral points are as follows: 34% at an 80% relative reduction, 49% at a 90% relative reduction, and 62% at a 100% relative reduction in reintervention versus standard bare-metal stent. The costs for treating the entire population who are eligible for stents with an SES thus decreases as the relative reduction in reintervention increases. The percentage of patients shifting from coronary artery bypass graft (CABG) to arrive at a cost-neutral point also decreases as the relative reduction in reintervention increases. THE COST OF RESTENOSIS Dr Steinberg: What assumptions did the authors make regarding the cost of managing restenosis? Were procedures other than percutaneous transluminal coronary angioplasty (PTCA) for example, brachytherapy, cutting balloons, stent within a stent considered for the treatment of restenosis? What percentage of PTCAs would be performed on an inpatient and outpatient basis to treat restenosis? How does the cost vary with regard to inpatient and outpatient procedures? How does the model that the authors used reflect the percentage of restenosis risk with those patients receiving a bare-metal stent and a drug-eluting stent? Dr Ruffy: The costs are the reimbursement rates by payors stated as diagnosis-related groups (DRGs) or case rates and limited to single- and multivessel CABG and angioplasty with stenting. The $9000 amount is the reimbursement cost of an angioplasty without stenting. For stented patients, $4480 per patient at 1.4 stents per patient would be added. DRG or case-rate reimbursement is based on the diagnosis and the proce- Advanced Studies in Medicine S609
dure, or stenting versus nonstenting. Payors who reimburse at a percentage of charge may reimburse at a higher rate and those that reimburse at a per diem rate would reimburse at a lower rate. Currently 85% to 90% of the patients treated with angioplasty receive a stent. The model assumes that any patient currently being treated with a stent would come into the model being treated with an SES. Brachytherapy is only indicated for in-stent restenosis. The model filters out previously treated restenosis. The choices of treatment in the model are angioplasty with stenting and CABG, all performed on an inpatient basis. Currently, less than 7% of patients are treated on an outpatient basis, so we have not considered this scenario. The model uses assumptions and formulae developed by David Cohen, MD, MSc, a well-known Harvard health economist. The probability of receiving CABG after the following events are assumed to be: Unsuccessful stenting procedure 2% Restenosis following initial intervention 8% Restenosis following 1st repeat PCI 39% Restenosis following 2nd repeat PCI 65% At 49% of the population being treated, there are no deaths assumed. At 100% of the population being treated, there is 1 death for the bare-stent treated population. IMPACT OF AVAILABILITY OF DRUG-ELUTING STENTS ON NUMBER OF PATIENTS UNDERGOING PTCA PLUS STENT Dr Steinberg: Please address whether the availability of drug-eluting stents will result in a shift of patients from (1) CABG to PTCA plus stent and/or (2) medical therapy to PTCA plus stent. Because physicians and facilities would lose revenue due to decreased admissions and procedures when drug-eluting stents are used, it is possible that providers would respond in compensatory ways that would increase their revenue as well as insurers costs. Dr Ruffy: The model assumes that the patients currently being treated by a stenting procedure would be treated with an SES as well as the probability of patients currently being treated with an invasive CABG procedure shifting to an SES. There are no assumptions concerning patients currently being treated with medical therapy alone who shift to a stenting procedure. If there is a shift from medical treatment to an SES, there may be an increase in cost to the payor; however, the decrease in patients being treated by CABG represents a potentially greater saving to payors. While it is likely that facilities will be facing reduced revenues, due to the decrease of CABG procedures that generate a greater profit margin than current bare-metal stenting procedures, increased revenues should be generated by the incremental reimbursement for drug-eluting stents. GENERALIZABILITY OF COST ASSUMPTIONS Dr Steinberg: I would like to know how representative the payment rates are for PTCA and CABG. A loss of 8.3 days for CABG and 2.3 days for PTCA seems to be high. Dr Ruffy: Payment rates and the length of stay are derived from a 7-state analysis of all 1999 payor data and includes 283 000 cases from 369 hospitals. DRGs 106, 107, 109, 516, 517 and 518 were included in the analysis. LATE RESTENOSIS Dr Steinberg: The analysis assumes that the incidence of late restenosis is equal in the 2 groups. If the drug-eluting stents delay rather than prevent restenosis, the cost effectiveness of them will be lower. Since we don t have enough experience with drug-eluting stents to know how durable their benefits are, this issue should be addressed in a sensitivity analysis. Dr Ruffy: Data from the First in Man study (FIM) (up to 3 years) and data from the RAVEL trial (up to 2 years) have shown that the SES does not just delay but prevents restenosis up to at least 3 years. Restenosis is a self-limited condition that typically presents within 6 to 12 months following percutaneous coronary interventions. REFERENCES 1. Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med. 1987;316:701-706. S610 Vol. 3 (6D) June 2003
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