(18) IN.PACT AV Access Trial: Economic Evaluation of Drug-Coated Balloon Treatment for Dysfunctional Arteriovenous Fistulae Based on 12-Month Clinical Outcomes

SECTION: TITLE
IN.PACT AV Access Trial: Economic Evaluation of Drug-Coated Balloon Treatment for Dysfunctional Arteriovenous Fistulae Based on 12-Month Clinical Outcomes

SECTION: ABSTRACT
Purpose:

To study, from a U.S. payer's perspective, the economic consequences of drug-coated balloon (DCB) versus standard percutaneous transluminal angioplasty (PTA) use for the treatment of stenotic lesions in dysfunctional hemodialysis arteriovenous fistulae. hemodialysis arteriovenous fistulae.

Materials and Methods:

Cost differences between DCBs and PTA at year 1 and beyond were calculated via 2 methods. The first approach used the mean absolute number of trial-observed access circuit reinterventions through 12 months (0.65 +- 1.05 vs 1.05 +- 1.18 events perThe first approach used the mean absolute number of trial-observed access circuit reinterventions through 12 months (0.65 +- 1.05 vs 1.05 +- 1.18 events per patient for DCBs and PTA, respectively) and projected treatment outcomes to 3 years. The second approach was based on the trial-observed access circuit primary patency rates at 12 months (53.8% vs 32.4%) and calculated the cost difference on the basis of previously published Medicare cost for patients who maintained or did not maintain primary patency. Assumptions regarding DCB device prices were tested in sensitivity analyses, and the numbers needed to treat were calculated.

Results:

Using the absolute number of access circuit reinterventions approach, the DCB strategy resulted in an estimated per-patient savings of $1,632 at 1 year and $4,263 at 3 years before considering the DCB device cost. The access circuit primary patency approach was associated with a per-patient cost savings of $2,152 at 1 year and $3,894 at 2.5 years of follow-up. At the theoretical DCB device reimbursement of $1,800, savings were $1,680 and $2,049 at 2.5 and 3 years, respectively. The one-year NNT of DCB compared to PTA was 2.48.

Conclusions:

Endovascular therapy for arteriovenous access stenosis with the IN.PACT AV DCB can be expected to be cost-saving if longer follow-up data confirm its clinical effectiveness.

SECTION: INTRO
In 2019, more than 500,000 patients with end-stage renal disease (ESRD) required hemodialysis in the United States. ESRD and hemodialysis not only present a dramatic clinical and quality-of-life challenge for patients but also create significant cost to the healthcare system. Medicare spent more than $94,000 per year per hemodialysis patient in 2019, amounting to total annual costs of more than $37 billion for Medicare fee-for-service beneficiaries alone. Approximately 65% of patients on hemodialysis with prevalent ESRD use an arteriovenous (AV) fistula (AVF) for vascular access. The costs associated with creating and maintaining vascular access required for hemodialysis comprise a sizable share of these annual costs and highlight the need for advances in treatment to improve outcomes and reduce costs. Over the last few years, several trials of new balloon-based and stent graft-based treatments for AVF stenosis have been conducted, including the IN.PACT AV Access study.

In the IN.PACT AV Access study, percutaneous transluminal angioplasty (PTA) with drug-coated balloons (DCBs) was recently shown to be superior to PTA with a standard uncoated, non-high-pressure PTA in treating dysfunctional AVFs. In that study, DCBs had a higher target lesion primary patency than PTA through 6 months (82.2% vs 59.5%; absolute risk difference 22.8%, with a 95% confidence interval (CI) of 12.8%-32.8%). The 12-month clinical outcomes have been reported in this issue of Journal of Vascular and Interventional Radiology. However, not much is known about the economic consequences of DCB use in this clinical indication.

Therefore, the objective of this study was to evaluate the long-term costs of DCBs compared with those of PTA for treating dysfunctional AVFs in the U.S. healthcare system using the IN.PACT AV balloon.

SECTION: METHODS
MATERIALS AND METHODS

Overview

This study and the underlying IN.PACT AV Access study were sponsored by Medtronic.This study and the underlying IN.PACT AV Access study were sponsored by Medtronic. Cost differences between the DCB and PTA strategies were estimated via 2 different analyses, both using the U.S. Medicare perspective for costs and the 12-month clinical results for outcomes.This study and the underlying IN.PACT AV Access study were sponsored by Medtronic. Cost differences between the DCB and PTA strategies were estimated via 2 different analyses, both using the U.S. Medicare perspective for costs and the 12-month clinical results for outcomes. In the first analysis, the DCB- and PTA-specific total treatment costs (including index procedure and access circuit reinterventions) were calculated using the reintervention rates from the clinical trial and the applicable Medicare reimbursement amounts, projecting costs through 3 years of follow-up. In the second analysis, the cost difference between the DCB and PTA strategies was calculated on the basis of the trial-observed 12-month access circuit primary patency (ACPP) rates and previously published AVaccess-related costs over 2.5 years in Medicare beneficiaries, associated with maintained versus lost primary patency. In addition, the number needed to treat (NNT) was calculated. Because no separate reimbursement exists for DCBs, the base case did not consider incremental device costs. However, scenario calculations were performed, exploring the effect of added cost to payers for the use of DCB devices.

Study Data

Analysis inputs are shown in Table 1. Clinical data and resource utilization for the DCB and PTA strategies were obtained from the 12-month data of the IN.PACT AV Access study. In brief, this was a prospective multicenter randomized clinical trial that evaluated the IN.PACT AV DCB (Medtronic Inc., Santa Rosa, California) versus PTA in participants with de novo or nonstented restenotic lesions up to 100 mm in length in AV dialysis fistulae. The trial randomized a total of 330 participants (n = 170 and n = 160 in the DCB and PTA groups, respectively). The primary safety endpoint was the rate of serious adverse events involving the AV access circuit through 30 days after the procedure. The primary effectiveness measure was the target lesion primary patency rate through 6 months, defined as freedom from clinically driven target lesion revascularization or access circuit thrombosis measured through 6 months after the procedure. Additional trial details have been previously published. The ethics committee or institutional review board (as appropriate for each study site) approved the IN.PACT AV Access study from which the clinical data for this analysis were obtained.

For the purposes of the present economic analyses, this study focused on the reintervention events and ACPP as the clinical outcomes because they are both directly associated with treatment cost and resource utilization. For reinterventions, details about the use of balloon procedures, stent procedures, and thrombectomy procedures were obtained from the trial data. In addition, the number of DCB catheters used in the DCB index procedure, the frequency of required surgical reinterventions, and the use of duplex ultrasound examinations in each strategy were captured.

For the first analysis, costs were based on the fiscal year 2020 Medicare fee schedules

For the first analysis, costs were based on the fiscal year 2020 Medicare fee schedulesFor the first analysis, costs were based on the fiscal year 2020 Medicare fee schedules (details available online on the article's Supplemental Material page at www.jvir.org). Because AVF interventions are performed in different settings of care:physician office, ambulatory surgery center (ASC), and hospital inpatient and outpatient settings:a weighted average of payment was estimated for the base case calculations on the basis of the Medicare site-of-service distribution (calendar year 2018 data). The costs of surgical reinterventions were determined on the basis of the types of surgical reinterventions performed and the corresponding Medicare payments. Duplex ultrasound costs were included only if performed in the office setting because they are not separately reimbursed in other settings.

For the second analytic approach, the previously reported vascular access costs from Thamer et al for participants who had maintained versus those who had not maintained AVF primary patency at 12-month follow-up were used because that cohort ("cohort 1") most closely resembled the current study population.

Model-Based Projections and Analysis Scenarios

The first analysis used a decision-analytic model that included "postendovascular intervention" and "death" as its 2 health states.The first analysis used a decision-analytic model that included "postendovascular intervention" and "death" as its 2 health states. Participants in the modeled cohorts progressed through these states on the basis of strategy-specific event rates, with a modeled cycle length of 1 month. Respective access circuit reintervention events were accounted for in each model cycle. Monthly reintervention events were modeled on the basis of the event rates observed at 6 and 12 months. For analysis purposes, the current study assumed the reported 6-month events to be equally distributed in that 6-month period. The same assumption was made for the incremental events in the subsequent 6-month period leading up to the reported 12-month data point. For subsequent model cycles up to the analysis horizon of 36 months, the participants who were alive were assumed to have a reintervention rate that resembled the year 1 events, with other effectiveness scenarios:reflecting uncertainty in the 1-year data and derived projections:being explored in extensive sensitivity analyses, including a diminishing DCB effect and fewer reintervention events with PTA. Furthermore, in addition to the weighted average cost across the different sites of care, costs were reported separately for each site of service.

Similar mortality rates were observed for the DCB and PTA at 12 months in the IN.PACT AV Access study; therefore, no survival difference between the 2 strategies was assumed. For survival projections, the age- and sex-matched mortality rates from U.S. life tables were used. These were adjusted through a hazard ratio to match the trial-observed mortality.

The cost difference between the DCB and PTA strategies at 36 months was the main economic outcome. Shorter analysis horizons were explored in the sensitivity analyses. All costs were discounted at 3% per annum, in line with recommendations promulgated by the U.S. Panel on Cost-Effectiveness and the relevant American College of Cardiology/American Heart Association statement.t Association statement. Scenario analyses included a decreased or lower relative clinical effectiveness in years 2 and 3; variation in the 12-month event rates; analyses based on the variation of sex, age, and mortality hazard ratio; as well as scenarios exploring the implication of potential additional payment for DCB devices.Scenario analyses included a decreased or lower relative clinical effectiveness in years 2 and 3; variation in the 12-month event rates; analyses based on the variation of sex, age, and mortality hazard ratio; as well as scenarios exploring the implication of potential additional payment for DCB devices.. Uncertainty in the number of access circuit reinterventions at 12 months, projected clinical events, and cost projections were additionally explored by plotting the calculated 95% CIs on the basis of the reported 12-month clinical data and evaluating significance.Uncertainty in the number of access circuit reinterventions at 12 months, projected clinical events, and cost projections were additionally explored by plotting the calculated 95% CIs on the basis of the reported 12-month clinical data and evaluating significance.

The second analysis did not require a projection or analysis model because the cost difference between the 2 strategies could be calculated directly from the trial-observed 12-month ACPP rates for DCB and PTA and the vascular access cost data by Thamer et al. The cost difference at 2.5 years of follow-up was calculated on the basis of the annualized cost by Thamer et al as well as the 1-year cost difference based on their reported 1-year costs. All costs were inflated from 2013 to 2019 dollars using the medical consumer price index. Trial-derived primary patency for each group and the annual costs for primary patency versus nonpatency were resampled 5,000 times; the total 1-year and 2.5-year costs were compared using the Wilcoxon rank sum test given nonnormally distributed data.

Additional analyses included the calculation of costs per reintervention avoided based on cost data from the main analysis and observed/projected reintervention events. Similarly, the NNT to avoid 1 reintervention was calculated on the basis of these event data.

Analyses were performed using Stata MP15 (StataCorp, College Station, Texas), JMP 15 (SAS Institute, Cary, North Carolina), and TreeAge Pro (TreeAge LLC, Williamstown, Massachusetts).

SECTION: RESULTS
RESULTS

The first analysis yielded a projected 3-year cost saving of $4,263 for the DCB strategy on the basis of a projected cumulative reduction of 1.06 reinterventions (1.70 for DCB vs 2.76 for PTA) over the analysis horizon. Savings accumulated over time, with projected 1- and 2-year per-patient savings of $1,632 and $3,038, respectively. The CIs of events and costs did not overlap, indicating statistically significant differences (P .025) (Fig 1; Supplemental Figure E2, available online at www.jvir.org).

The second analysis, based on a bootstrapped dataset, found a mean 12-month cost of $12,207 (95% CI, $11,751-$12,656) per patient for the DCB strategy and a mean 12-month cost of $14,359 (95% CI, $13,807-$14,818) per patient for the PTA strategy. The mean cost difference was $2,152 (P .0001). For the 30-month horizon, the mean costs were $24,722 (95% CI, $23,418-$25,671) and $28,615 (95% CI, $27,654-$29,906) for DCB and PTA strategies, respectively, with a mean cost difference of $3,893 (P .0001) (Fig 2; Supplemental Figure E3, available online at www.jvir.org).

Scenario and Sensitivity Analyses

Performing site-of-service-specific calculations of the first analysis, as opposed to the blended scenario, resulted in the following projected cost savings over the 3-year horizon: $1,925 for the physician office setting, $3,066 for the ASC setting, $6,095 for the hospital outpatient setting, and $21,307 for the hospital inpatient setting. Cost savings at shorter analysis horizons are included in Figure E1 (available online at www.jvir.org).

The effects of changes in clinical and cost assumptions on cost difference between the strategies and on the cumulative difference in projected event rates at 3 years in the first analysis are shown in Table 2. Without the consideration of additional device payment for the DCB strategy, DCBs remained cost saving across all the studied scenarios and at all time frames between 1 and 3 years. Savings were more pronounced with longer follow-up. Hypothetical additional payment for DCBs, between $1,800 and $2,200 per device, led to smaller cost savings at 3 years. A payment of $1,800 per DCB device:based on manufacturer-provided list price:led to approximate cost neutrality between 1 and 2 years but was associated with higher incremental cost for the DCB strategy at 1 year. The use of 1 device per procedure, as opposed to the 1.23 devices assumed in the base case, would lead to more pronounced savings.

NNT, Budget Impact, and Threshold Analysis

The NNT to avoid 1 reintervention over a 1-year period was 2.48. Under constant event rate assumptions beyond 1 year, the NNT was reduced to 1.34 over a 2-year horizon and to 0.94 over a 3-year horizon.

Under the assumption that 50% of the current approximately 233,000 annual access circuit PTA procedures would be performed with DCBs instead of PTA, Medicare could expect to save between $190 million (based on the first analysis) and $250 million (based on the second analysis) per year. Over 3 years, potential savings are projected to be approximately $497 million on the basis of the first analysis.

Considering a 2.5-year analysis horizon, it was projected that Medicare could expect cost savings as long as the potential additional payment for DCBs is lower than $2,820 or $3,165 per device based on the 2 analyses, respectively.

SECTION: DISCUSS
DISCUSSION

Using 2 different analytic approaches, this study explored the economic consequences of DCB use instead of PTA in the treatment of dysfunctional AVFs. The clinical effectiveness improvement documented through 12 months in the IN.PACTAV Access study was found to be associated with a meaningful savings potential to Medicare. The first:main:analysis required assumptions about DCB effectiveness beyond the currently available trial follow-up, whereas the second analysis facilitated projections through 2.5 years based on actual trial-demonstrated ACPP rates at 1 year.

Both analyses:despite taking different analytic approaches:found directionally similar cost differences of more than $3,800 at follow-up between 2.5 and 3 years. These projected cost savings for Medicare will be lowered by any incresmental payment for DCB therapy. To assess the implications of such added costs, several hypothetical scenarios were explored and found that DCBs remain cost saving at 2.5 and 3 years for costs up to $2,800 per device.

There are significant differences in reimbursement by site of service for dialysis access maintenance using angioplasty with PTA (with or without DCB). In 2018, approximately 50% of all angioplasty procedures for dialysis access maintenance were performed in the physician office setting for a payment of $1,300 per procedure. In 2018, reimbursement was higher in other settings: $2,142 in the ASC setting (19% of angioplasty procedures), $4,953 for outpatient treatment in hospitals (26% of angioplasty procedures), and $20,841 for hospital inpatient treatment (4% of angioplasty procedures). The site-of-service-specific analyses of this study found substantial variation in projected Medicare savings and may provide useful additional information for policy makers and providers because therapy adoption and potential reimbursement scenarios were considered (Supplemental Figure E1, available online at www.jvir.org). Based on past experiences with DCB reimbursement for the treatment of the femoropopliteal artery, patient access to DCBs in a physician office setting is expected to be limited if not nonexistent because of the steep reimbursement barrier. It remains to be seen whether appropriate reimbursement mechanisms are implemented that balance the projected savings to Medicare with the added device cost that providers would incur if they adopt DCBs as the more efficacious clinical strategy and without which Medicare would not be able to experience the full extent of the savings.

The projection in the first analysis assumed that event rates beyond 12 months would be similar to those observed in the first year. This assumption for the base case was chosen as a "middle-of-the-road" estimate in light of conflicting evidence available from prior studies. In a retrospective single-center study of 720 patients with AVF, the clinical effectiveness of repeated percutaneous intervention diminished with each successive procedure. This suggests an increasing reintervention burden over time. At the same time, evidence from the 144 participants in the PTA group of the recent Lutonix AV Randomized Trial suggests a somewhat lower number of reinterventions needed to maintain target lesion primary patency in the second year than in the first year. The scenario analyses performed in this study provide insight into the implication of changes in the clinical performance assumptions. In this context, it is noteworthy that the second analysis, which relied only on trial-observed 12-month primary patency rates without any further assumptions, found cost savings for DCB that were slightly higher than the savings projected in the first analysis, providing some assurance that the assumptions in this (main) analysis were reasonable.

The findings of the current study are directionally in line with a prior European study evaluating the clinical effectiveness and cost effectiveness of DCB use for the treatment of AVF failure. Kitrou et al performed a cost-effectiveness analysis on the basis of a single-institution randomized controlled trial comparing participants treated with DCB or PTA (n = 20 in each group). They found DCBs to be associated with cost savings and outcome improvement, which justified the added cost of DCBs in a European context.

The reintervention cost in the main analysis, with an estimated 1-year cost for index plus reintervention procedures of approximately $5,500-$6,800, is lower than the total vascular access costs documented in prior studies. For example, the previously referenced study by Nordyke et al found vascular access costs in the first and second year to amount to $14,526 and $6,444, respectively (in 2017 U.S. dollars). Similarly, the study by Thamer et al used in the second analysis found the first year costs of $6,442 for patients who maintained primary patency and $15,009 for patients who lost patency, followed by $4,279 and $7,402, respectively, in the second year. This, again, suggests that the cost difference in the main analysis of the current study, relying only on reintervention cost, may be conservative. On the other hand, the significant downward trend in access-related costs between years 1 and 2 observed by both Nordyke et al and Thamer et al suggests that in the immediate months following AVF creation, higher costs are incurred that are tied to complications other than those requiring endovascular reintervention. In turn, this suggests that the vascular access costs in the second year may be more closely related to reintervention costs, which would explain the closer resemblance with the costs found in this study's main analysis.

Among the strengths of the current analysis is its reliance on clinical data from a contemporary and independently adjudicated randomized controlled trial. Furthermore, the approach to pursue 2 independent analytic approaches:one of them relying on current fee schedules and the other on a previously published analysis of Medicare costs for patients maintaining or not maintaining ACPP at 1 year:led to very similar calculated cost differences.

At the same time, the analysis is subject to several limitations. First, a multiyear projection was performed on the basis of the 1-year trial data. However, it is a requirement for health-economic analyses to explore the potential effect of interventions beyond the follow-up data collected in a trial. This is particularly important when the intervention can be expected to have additional clinical benefit beyond the current follow-up period. The extensive sensitivity analyses document the effect of differing assumptions about longer-term effectiveness. Second, this analysis was based on cost to Medicare as the primary payer, evaluated on the basis of reimbursement amounts paid by Medicare, as opposed to a detailed microcosting performed alongside the trial. However, the analysis perspective in this study was the payer perspective, with the primary objective to evaluate the cost implications to Medicare. Third, although the analysis uses national average cost inputs, some regional differences may exist in specific geographies. Fourth, on this basis, this analysis is also more limited than a full cost-utility analysis that would also estimate differences in quality-adjusted life year (QALY) gain. Considering no observed mortality difference at 12 months, it is safe to assume that any QALY gain between the 2 strategies could be expected to be derived from a lower reintervention burden. For example, in the IN.PACT SFA study, a QALY decrement of 0.06 QALYs was calculated to be associated with each target lesion revascularization. Finally, the findings of this study are based on data from the IN.PACT AVAccess study and may, therefore, not apply to other DCB devices and to cohorts whose characteristics and treatment approaches differ from those of the IN.PACT AV Access study.

In summary, the treatment of AVFs with the IN.PACT AV DCB may lead to substantive per-patient and health system savings with concurrent improvement in patient outcome. This analysis should be updated when longer-term follow-up data from the pivotal trial become available.

SECTION: SUPPL
Supplementary Material

Figures E1-E3 and Tables E1 and E2 can be found by accessing the online version of this article on www.jvir.org and selecting the Supplemental Material tab.

SECTION: ABBR
ABBREVIATIONS

ACPP

access circuit primary patency

ASC

ambulatory surgery center

AV

arteriovenous

AVF

arteriovenous fistula

CI

confidence interval

DCB

drug-coated balloon

ESRD

end-stage renal disease

NNT

number needed to treat

PTA

percutaneous transluminal angioplasty

QALY

quality-adjusted life year

SECTION: FIG
Projected cumulative access circuit reintervention events and costs for percutaneous transluminal angioplasty (PTA) and drug-coated balloons (DCBs) through 36 months. (a) Projected cumulative access circuit reintervention events and (b) resulting cumulative per-patient costs for PTA and DCB through 36 months. Six- and 12-month clinical events as observed in the IN.PACT AV Access study; subsequent clinical events projected assuming that the event rates and treatment effect observed at 1 year are maintained. The 95% confidence interval (CI) calculated on the basis of 12-month clinical event rates. Note: These payer costs do not take into account any DCB device reimbursement because there is currently no incremental payment for the use of DCB.

Trial-observed 12-month access circuit primary patency and projected 12- and 30-month total vascular access costs. Resulting per-patient cost differences are shown between percutaneous transluminal angioplasty (PTA) and drug-coated balloons (DCBs) at 12 and 30 months.

SECTION: TABLE
Analysis Inputs

Variable Definition Source Clinical parameters Age (y) 65.6 +- 13.3 Studies by Lookstein et al or Holden et al Sex (% male) 64.5% Studies by Lookstein et al or Holden et al Mortality HR of persons with ESRD on hemodialysis, relative to general population mortality 6.75 Calibrated on the basis of the pooled mortality estimate at 12 mo as reported in the study by Falk et al. Effectiveness: access circuit reintervention events PTA, at 6 mo 0.65 +- 0.8 Study by Lookstein et al. DCB, at 6 mo 0.32 +- 0.7 Study by Lookstein et al. Difference in access circuit reintervention events at 6 mo -0.33 (P .001) Study by Lookstein et al. PTA, at 12 mo 1.05 +- 1.18 Study by Holden et al. DCB, at 12 mo 0.65 +- 1.05 Study by Holden et al. Difference in access circuit reintervention events at 12 mo -0.40 (P .001) Study by Holden et al. Effectiveness: access circuit primary patency PTA, 12 mo 32.4% Study by Holden et al. DCB, 12 mo 53.8% Study by Holden et al. Difference in access circuit primary patency at 12 mo 21.4%. (P .001) Study by Holden et al. Use of devices per respective reintervention procedure (full details inTables E1 and E2) DCB 1.23 Use in the IN.PACT AV Access trial, post hoc analysis. BMS (used in 10% of reinterventions) 1.0 Use in the IN.PACT AV Access trial, post hoc analysis. Cost parameters: first (main) analysis Medicare fee schedule amounts, weighted average PTA procedure cost $3,332 Weighted average of Medicare calendar year 2020 payments, considering the following site-of-service mix: 51%, physician office; 26%, hospital outpatient; 19%, ambulatory surgery center; and 4%, hospital inpatient. Respective site-of-service amounts reflect national average payment (details shown in Supplemental Materials). DCB procedure cost $3,332 (+DCB additional payment where explored) Same as PTA procedure cost (base case), plus additional DCB costs (scenario analyses). Reintervention cost $4,113 Weighted average payments as described earlier, assuming 85% PTA, 10% stent placement, and 5% thrombectomies and surgical interventions as observed in the trial (details shown in Supplemental Materials). Cost parameters: second analysis Vascular access cost in year 1 for patients who maintained access circuit primary patency at 12 mo after AVF creation $7,561 Study by Abdel-Kader et al, inflated from 2013 to 2019 U.S. dollars using the medical consumer price index. Vascular access cost in year 1 for patients who lost primary patency at 12 mo after AVF creation $17,617 Study by Abdel-Kader et al, inflated from 2013 to 2019 U.S. dollars using the medical consumer price index. Vascular access cost over 2.5 years for patients who maintained primary patency at 12 mo after AVF creation $16,315 Calculated on the basis of the annualized cost reported in the study by Abdel-Kader et al, inflated from 2013 to 2019 U.S. dollars using the medical consumer price index. Vascular access cost over 2.5 years for patients who lost access circuit primary patency at 12 mo after AVF creation $34,511 Calculated on the basis of the annualized cost reported in the study by Abdel-Kader et al, inflated from 2013 to 2019 U.S. dollars using the medical consumer price index. Discounting Discount rate on costs, p.a. 3.0% Recommendations of the Panel on Cost-Effectiveness analysis.

AVF = arteriovenous fistula; BMS = bare-metal stent; DCB = drug-coated balloon; ESRD = end-stage renal disease; HR = hazard ratio; p.a. = annually; PTA = percutaneous transluminal angioplasty.

Scenario and Sensitivity Analyses: Cost Difference for DCB startegy versus PTA Strategy at Years 1, 2, and 3 and Projected Difference in Cumulative Reintervention Events at 3 Years

Scenario Cost difference DCB vs PTA ($) Three-year difference in cumulative reintervention events 1 y 2 y 3 y 3 y with $1,800 DCB cost considered Base case -1,632 -3,038 -4,263 -2,049 -1.06 Mortality HR 8.0 (3-y survival, 69%) -1,621 -2,986 -4,151 -1,937 -1.03 Mortality HR 5.0 (3-y survival, 80%) -1,648 -3,113 -4,426 -2,212 -1.10 Age 53 (1 standard deviation below the mean) -1,669 -3,208 -4,637 -2,423 -1.14 Age 79 (1 standard deviation above the mean) -1,487 -2,404 -2,977 -763 -0.77 100% male -1,623 -2,993 -4,166 -1,952 -1.04 100% female -1,650 -3,120 -4,441 -2,227 -1.10 No incremental benefit for DCB beyond year 2 -1,632 -3,038 -3,078 -864 -0.75 No incremental benefit for DCB beyond year 1 -1,632 -1,678 -1,718 496 -0.40 PTA events in years 2 and 3 10% lower than the first year, DCB events 10% higher than the first year -1,632 -2,466 -3,192 -978 -0.78 PTA events in years 2 and 3 15% lower than the first year, DCB events 15% higher than the first year -1,632 -2,179 -2,656 -442 -0.64 PTA events in years 2 and 3 20% lower than the first year, DCB events 20% higher than the first year -1,632 -1,893 -2,120 94 -0.51 Additional incremental benefit for DCB in years 2 and 3 (0.50 annual events instead of 0.65) -1,632 -3,535 -5,192 -2,978 -1.30 Revascularization events in years 2 and 3 at 80% of their respective first-year values -1,632 -2,766 -3,754 -1,540 -0.93 Revascularization events in years 2 and 3 at 80% and 60% of their respective first-year values -1,632 -2,766 -3,517 -1,303 -0.87 Revascularization events in years 2 and 3 at 120% of their respective first-year values -1,632 -3,310 -4,772 -2,558 -1.19 Cost undiscounted -1,651 -3,122 -4,442 -2,228 -1.06 Cost discounted at 5% p.a. -1,620 -2,986 -4,153 -1,939 -1.06 Additional payment for DCB $1,800 (and use of 1.23 DCB devices per procedure) 582 -824 -2,049 N/A (see left) -1.06 Additional payment for DCB $2,000 (and use of 1.23 DCB devices per procedure) 828 -578 -1,803 N/A (see left) -1.06 Additional payment for DCB $2,200 (and use of 1.23 DCB devices per procedure) 1,074 -332 -1,557 N/A (see left) -1.06 Additional payment for DCB $1,800 (and use of 1.0 DCB devices per procedure) 168 -1,238 -2,463 N/A (see left) -1.06 Additional payment for DCB $2,000 (and use of 1.0 DCB devices per procedure) 368 -1,038 -2,263 N/A (see left) -1.06 Additional payment for DCB $2,200 (and use of 1.0 DCB devices per procedure) 568 -838 -2,063 N/A (see left) -1.06

Note-Analyses refer to the main analysis.

DCB = drug-coated balloon angioplasty; HR = hazard ratio; p.a. = annually; PTA = percutaneous transluminal angioplasty.