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A cost-utility analysis of transcatheter versus surgical aortic valve replacement for the treatment of aortic stenosis in the population with intermediate surgical risk

  • Derrick Y. Tam
    Affiliations
    Division of Cardiac Surgery, Schulich Heart Centre, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada

    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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  • Avery Hughes
    Affiliations
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada

    Program of Child Health Evaluative Services, The Hospital for Sick Children, Peter Gilgan Centre For Research and Learning, University of Toronto, Toronto, Ontario, Canada
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  • Stephen E. Fremes
    Affiliations
    Division of Cardiac Surgery, Schulich Heart Centre, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada

    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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  • Saerom Youn
    Affiliations
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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  • Rebecca L. Hancock-Howard
    Affiliations
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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  • Peter C. Coyte
    Affiliations
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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  • Harindra C. Wijeysundera
    Correspondence
    Address for reprints: Harindra C. Wijeysundera, MD, PhD, Schulich Heart Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Room A202, Toronto, Ontario M4N 3M5, Canada.
    Affiliations
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada

    Program of Child Health Evaluative Services, The Hospital for Sick Children, Peter Gilgan Centre For Research and Learning, University of Toronto, Toronto, Ontario, Canada

    Division of Cardiology, Schulich Heart Centre, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
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Open ArchivePublished:February 02, 2018DOI:https://doi.org/10.1016/j.jtcvs.2017.11.112

      Abstract

      Objective

      Although transcatheter aortic valve implantation has been shown to be noninferior to surgical aortic valve replacement in patients with severe aortic stenosis at intermediate surgical risk, the cost-effectiveness of this strategy in this population is unknown. Our objective was to conduct a cost-utility analysis comparing transcatheter aortic valve implantation with surgical aortic valve replacement in the population with intermediate risk severe aortic stenosis.

      Methods

      A fully probabilistic Markov model with 30-day cycles was constructed from the Canadian third-party payer's perspective to estimate the difference in cost and effectiveness (measured as quality-adjusted life years) of transcatheter aortic valve implantation versus surgical aortic valve replacement for intermediate-risk patients over a lifetime time horizon, discounted at 1.5% per annum. Clinical trial data from The Placement of Aortic Transcatheter Valve 2 informed the efficacy inputs. Costs (adjusted to 2016 Canadian dollars) were obtained from the Canadian Institute of Health Information and the Ontario Schedule of Benefits. Incremental cost-effectiveness ratios were calculated.

      Results

      In the base-case analysis, total lifetime costs for transcatheter aortic valve implantation were $10,548 higher than surgical aortic valve replacement but added 0.23 quality-adjusted life years, for an incremental cost-effectiveness ratio of $46,083/quality-adjusted life-years gained. Deterministic 1-way analyses showed that the incremental cost-effectiveness ratio was sensitive to rates of complications and cost of the transcatheter aortic valve implantation prosthesis. There was moderate-to-high parameter uncertainty; transcatheter aortic valve implantation was the preferred option in only 52.7% and 55.4% of the simulations at a $50,000 and $100,000 per quality-adjusted life years willingness-to-pay thresholds, respectively.

      Conclusions

      On the basis of current evidence, transcatheter aortic valve implantation may be cost-effective for the treatment of severe aortic stenosis in patients with intermediate surgical risk. There remains moderate-to-high uncertainty surrounding the base-case incremental cost-effectiveness ratio.

      Key Words

      Abbreviations and Acronyms:

      AS (aortic stenosis), FDA (Food and Drug Administration), GDP (gross domestic product), ICER (incremental cost-effectiveness ratio), ICU (intensive care unit), PARTNER (The Placement of Aortic Transcatheter Valve), QALY (quality-adjusted life year), QoL (quality of life), RCT (randomized clinical trial), SAVR (surgical aortic valve replacement), STS (Society of Thoracic Surgeons), TAVI (transcatheter aortic valve implantation), WTP (willingness-to-pay)
      Figure thumbnail fx1
      Cost-effectiveness acceptability curve for TAVI versus SAVR.
      TAVI may be cost-effective in the population with intermediate surgical risk compared with SAVR.
      Clinical trials in patients with severe AS at intermediate surgical risk showed noninferiority when TAVI was compared with SAVR. However, the cost-effectiveness of TAVI in this population was not known. This analysis showed that TAVI may be an economically attractive option compared with SAVR in this population.
      See Editorial Commentary page 1989.
      See Editorial page 1977.
      Traditionally, surgical aortic valve replacement (SAVR) was considered the gold standard for the treatment of severe aortic stenosis (AS). However, transcatheter aortic valve implantation (TAVI) has emerged as the treatment of choice for patients with severe symptomatic AS who are inoperable or at high surgical risk.
      • Leon M.B.
      • Smith C.R.
      • Mack M.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • et al.
      Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.
      • Smith C.R.
      • Leon M.B.
      • Mack M.J.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • et al.
      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
      Numerous previously published economic studies suggest that TAVI is cost-effective in both the inoperable and high-risk populations.
      • Sud M.
      • Tam D.Y.
      • Wijeysundera H.C.
      The economics of transcatheter valve interventions.
      The exponential growth of TAVI has led to indication expansion to low-risk patients. A landmark randomized clinical trial (RCT) conducted in patients with intermediate surgical risk (Society of Thoracic Surgeons [STS] Predicted Risk of Mortality at 30 days 4%-8%) showed noninferiority for TAVI compared with SAVR.
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
      These findings have been reinforced by a number of propensity-matched studies and meta-analyses,
      • Tam D.Y.
      • Vo T.X.
      • Wijeysundera H.C.
      • Ko D.T.
      • Rocha R.V.
      • Friedrich J.
      • et al.
      Transcatheter vs surgical aortic valve replacement for aortic stenosis in low-intermediate risk patients: a meta-analysis.
      all of which have led to regulatory approval in the United States by the Food and Drug Administration (FDA) for this expanded indication.
      The intermediate-risk patients differ from the higher-risk population in several ways that may affect costs and outcomes. In particular, given that this population may be younger with fewer comorbidities, complication rates and length of hospital stay are likely to be different. Although the intermediate-risk population represents an emerging indication for TAVI, the cost-effectiveness of TAVI compared with SAVR is not known in this patient population. Accordingly, to address this gap in knowledge, we conducted a formal cost-utility analysis incorporating both lifetime costs and benefits to determine the cost-effectiveness of TAVI compared with SAVR in the intermediate-risk population from the Canadian third-party payer perspective.

      Materials and Methods

       Model Overview

      A fully probabilistic Markov model with cycle lengths of 30 days was constructed from the Canadian third-party payer's perspective to estimate the cost and effectiveness of TAVI versus SAVR for the intermediate-risk patient population over a lifetime time horizon. Under Canada's universal health care plan, the provinces are responsible for all care delivery; thus, in Ontario, the third-party payer is the Ministry of Health and Long Term Care. The primary cost outcome was total lifetime cost measured in 2016 Canadian Dollars and the primary effectiveness outcome was quality-adjusted life-years (QALYs). QALYs were obtained by multiplying the time spent in a particular health state with the quality weight for that respective health state. The incremental cost-effectiveness ratio (ICER) was calculated by taking the differences in lifetime costs between the 2 treatment groups (ie, incremental costs) and dividing by the differences in lifetime benefits (ie, incremental effectiveness, measured in QALYs). All outcomes and costs were discounted at 1.5% per annum in accordance with the Canadian Agency for Drugs and Technologies in Health guidelines.

      Canadian Agency for Drugs and Technologies. Guidelines for the Economic Evaluation of Health Technologies: Canada. 4th ed. Ottawa, Canada: CADTH; 2017.

       Model Structure

      All patients entered the model in the procedural state (TAVI or SAVR) and were at risk for clinically relevant short-term complications (major bleeding, acute kidney injury, vascular injury, atrial fibrillation, nondisabling stroke, rehospitalization) and long-term complications (death, dialysis, and disabling stroke).
      After the procedural state, all patients transitioned into 1 of 4 long-term states (alive and well, disabling stroke, dialysis, or death) as shown in Figure 1. Repeat hospitalization was a transition for which a patient would remain for a proportion of 1-cycle. Patients transitioned between these long-term states on the basis of efficacy data from the results of the recently published The Placement of Aortic Transcatheter Valve (PARTNER) 2 Trial. Transition probabilities between the alive and well state and the various complication states (excluding death) occurred only in the first 2 years of the model. After 2 years, we made the conservative assumption that the rates of complications were assumed to be equivalent in both the TAVI and SAVR arms. In addition, after 2 years, mortality rates in the model were based on 2010-2012 age- and gender- specific Canadian life tables given the absence of clinical trial data from the PARTNER 2 study beyond the 2-year follow-up.
      Statistics Canada
      Life Tables, Canada, Provinces and Territories 2010 to 2012.
      When transition probabilities were not available from PARTNER 2, published results from the literature for similar patient populations were used as described next.
      Figure thumbnail gr1
      Figure 1A state diagram of the Markov model. All patients started the model in the procedural state and transitioned to one of the long-term health states after 30 days postprocedure. With the exception of the dead state, patients transitioned between the different states every 30 days according to efficacy data obtained from the PARTNER 2 Trial.

       Clinical Efficacy Inputs

       Trial overview

      The PARTNER 2 Trial was a multicenter RCT of 57 centers in the United States and Canada comparing TAVI with SAVR in the intermediate surgical risk population (defined as STS Predicted Risk of Mortality 4 of 8% at 30 days). A total of 2032 patients at intermediate surgical risk were randomized to TAVI (n = 1011) or SAVR (n = 1021) and followed for the primary outcome of all-cause death or disabling stroke at 2 years using a noninferiority design. The average STS risk scores in both groups were similar (TAVI 5.8 ± 2.1, SAVR 5.8 ± 1.9), and the average age of the cohort was 81.5 ± 6.7 years and 81.7 ± 6.7 years in the TAVI and SAVR groups, respectively. In the TAVI group, patients underwent transfemoral or transthoracic placement of the balloon-expandable Sapien XT valve system (Edwards Lifesciences, Irvine, Calif).

       Efficacy end points

      The 30-day clinical end points were obtained from the PARTNER 2 Trial intention-to-treat cohort: death from any cause, any stroke, disabling stroke, nondisabling stroke, rehospitalization, major vascular complication, life-threatening or disabling bleed, acute kidney injury, and new-onset atrial fibrillation (Table E1). After 30 days, transition probabilities were based on 1-year and 2-year end points from the trial. We excluded patients who had an event at 30 days and 1 year from both the numerator and denominator of cumulative long-term probabilities (1 year and 2 years, respectively) to avoid double counting patient events as described in a previous cost-analysis.
      • Doble B.
      • Blackhouse G.
      • Goeree R.
      • Xie F.
      Cost-effectiveness of the Edwards SAPIEN transcatheter heart valve compared with standard management and surgical aortic valve replacement in patients with severe symptomatic aortic stenosis: a Canadian perspective.
      The proportion of patients with acute kidney injury progressing to dialysis was not provided in the PARTNER 2 Trial and was estimated from the PARTNER 1A trial; we used the same proportion in both groups.
      • Smith C.R.
      • Leon M.B.
      • Mack M.J.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • et al.
      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
      The probability of death during long-term dialysis was estimated from the published literature,
      • Foley R.N.
      • Gilbertson D.T.
      • Murray T.
      • Collins A.J.
      Long interdialytic interval and mortality among patients receiving hemodialysis.
      and the probability of death in patients with long-term strokes was also obtained from the literature.
      • Brønnum-Hansen H.
      • Davidsen M.
      • Thorvaldsen P.
      Danish MONICA Study Group. Long-term survival and causes of death after stroke.

       Cost inputs

      Up-front procedural costs included the following: TAVI system, SAVR valve, interventional cardiology procedural fees, surgeon fee, surgical assistant fee, anesthesiologist fee, ward, and intensive care unit (ICU) stay (Table 1). On the basis of input from TAVI implanters, the corresponding billing codes from the Ontario Schedule of Benefits used for TAVI and SAVR were determined.
      Ministry of Health Long Term Care
      Schedule of Benefits.
      Ward stay and ICU stay costs were obtained from St Michael's Hospital (Toronto, Ontario, Canada) (Cardiovascular ICU Unit Clerk, St Michael's Hospital, personal communication, November 2015). Length of stay in the ICU and ward was obtained from PARTNER 2.
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
      Costs for both the TAVI valve system and the surgical valve were obtained from the device manufacturer, Edwards Lifesciences (Edwards Life Sciences Market Access Team, personal communication, November 2016). The costs for periprocedural complications were obtained from the 2014 Canadian Institute for Health Information Patient Cost Estimator Case Mix Group for those aged more than 80 years in Ontario (Table 2).
      Canadian Institute for Health Information
      CIHI Patient Cost Estimator Website.
      Canadian Institute for Health Information
      Patient Cost Estimator: Methodological Notes and Glossary.
      Costs for long-term complication states of disabling stroke and dialysis were estimated from the literature,
      • Wong B.
      • Courtney M.
      • Pauly R.P.
      • Jindal K.
      • Klarenbach S.
      Cost analysis of in-centre nocturnal compared with conventional hemodialysis.
      • Ohinmaa A.
      • Zheng Y.
      • Jeerakathil T.
      • Klarenbach S.
      • Häkkinen U.
      • Nguyen T.
      • et al.
      Trends and regional variation in hospital mortality, length of stay and cost in hospital of ischemic stroke patients in Alberta accompanying the provincial reorganization of stroke care.
      whereas hospitalization was estimated from Canadian Institute for Health Information Patient Cost Estimator 2014. All costs were inflated to 2016 Canadian dollars using the Bank of Canada Consumer Price Index ($1.00 Canadian = $0.76 US Dollar [Bank of Canada Currency Exchange Rate, January 7, 2017]).
      Table 1Procedure-related costs and resources
      ProcedureTAVISAVR
      ResourceCost (SD)Mean units (SD)SourceCost (SD)Mean units (SD)Source
      Valve$24,000.001.004Edwards Lifesciences (Irvine, Calif)$60001Edwards Lifesciences
      Ward stay$945 (203)/d4 (1.33) dSt Michael's Hospital$945 (203)/d5 (1.67) dSt Michael's Hospital
      ICU stay$3161 (1283)/d2 (0.67) dSt Michael's Hospital$3161 (1283)/d4 (1.33) dSt Michael's Hospital
      Aortic valve replacement - Surgeon fee$10371OHIP R738$14031OHIP R738, E650
      First assist fee
      Payment for assistants and anesthesiology is based on initial baseline units for a procedure and the amount of time spent performing the procedure (estimated total procedural time as 3 ± 1 hours for TAVI and 5 ± 1.67 hours for SAVR).
      $12/unit42 unitsOHIP R738$12.04/unit66 unitsOHIP R738
      Second assist fee
      Payment for assistants and anesthesiology is based on initial baseline units for a procedure and the amount of time spent performing the procedure (estimated total procedural time as 3 ± 1 hours for TAVI and 5 ± 1.67 hours for SAVR).
      $12/unit42 unitsOHIP R738$12.04/unit66 unitsOHIP R738
      Aortic valve replacement – Anesthesia
      Payment for assistants and anesthesiology is based on initial baseline units for a procedure and the amount of time spent performing the procedure (estimated total procedural time as 3 ± 1 hours for TAVI and 5 ± 1.67 hours for SAVR).
      $15/unit60 unitsOHIP R738$15.01/unit84 unitsOHIP R738
      Insertion of temporary pacemaker wire$1540.5OHIP Z443
      Angiogram$1191OHIP G297
      Percutaneous angioplasty of the aortic valve$4881OHIP Z448A
      Retrograde aortic left heart catheterization$2100.5OHIP Z440
      Total procedural cost$40,274$29,856
      TAVI, Transcatheter aortic valve implantation; SAVR, surgical aortic valve replacement; SD, standard deviation; ICU, intensive care unit; OHIP, Ontario Health Insurance Benefit Schedule of Benefit.
      Payment for assistants and anesthesiology is based on initial baseline units for a procedure and the amount of time spent performing the procedure (estimated total procedural time as 3 ± 1 hours for TAVI and 5 ± 1.67 hours for SAVR).
      Table 2Cost and utilities for short-term transitions and long-term health states
      State/transitionCost (SD)SourceUtility (SD)Source
      Alive/well - SAVR0NA<7 mo: 0.68 (0.24)

      7-12 mo: 0.75 (0.27)

      >12 mo: 0.74 (0.23)
      Reynolds and colleagues
      • Reynolds M.R.
      • Magnuson E.A.
      • Wang K.
      • Thourani V.H.
      • Williams M.
      • Zajarias A.
      • et al.
      Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis.
      Alive/well - TAVI0NA<7 mo: 0.74 (0.24)

      7-12 mo: 0.76 (0.20)

      >12 mo: 0.75 (0.22)
      Reynolds and colleagues
      • Reynolds M.R.
      • Magnuson E.A.
      • Wang K.
      • Thourani V.H.
      • Williams M.
      • Zajarias A.
      • et al.
      Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis.
      Long-term costs and utilities (per cycle)
       Hospitalization$25,255 (8418)CIHI 2014 PCE0.56 (0.23)Ambrosy and colleagues
      • Ambrosy A.P.
      • Hernandez A.F.
      • Armstrong P.W.
      • Butler J.
      • Dunning A.
      • Ezekowitz J.A.
      • et al.
      The clinical course of health status and association with outcomes in patients hospitalized for heart failure: insights from ASCEND-HF.
       Dialysis$15,898 (5299)Wong and colleagues (2014)
      • Wong B.
      • Courtney M.
      • Pauly R.P.
      • Jindal K.
      • Klarenbach S.
      Cost analysis of in-centre nocturnal compared with conventional hemodialysis.
      0.44 (0.32)Lee and colleagues
      • Lee A.J.
      • Morgan C.L.
      • Conway P.
      • Currie C.J.
      Characterisation and comparison of health-related quality of life for patients with renal failure.
       Disabling stroke$3260 (1087)Ohinmaa and colleagues (2016)
      • Ohinmaa A.
      • Zheng Y.
      • Jeerakathil T.
      • Klarenbach S.
      • Häkkinen U.
      • Nguyen T.
      • et al.
      Trends and regional variation in hospital mortality, length of stay and cost in hospital of ischemic stroke patients in Alberta accompanying the provincial reorganization of stroke care.
      0.39 (0.12)Tengs and Lin
      • Tengs T.O.
      • Lin T.H.
      A meta-analysis of quality-of-life estimates for stroke.
      Transition costs and rewards
       Disabling stroke$9958 (3319)
      Average of “average of hemorrhagic event” and “ischemic event of CNS” in Ontario.
      CIHI 2014 PCENA
      Transition into disabling stroke was assigned only transition costs because it is a long-term state and disutility is captured in utility assigned to disabling stroke state.
      NA
       Hospitalization$25,255 (8418)CIHI 2014 PCE−0.1276 (0.0259)Lanitis and colleagues
      • Lanitis T.
      • Cotté F.E.
      • Gaudin A.F.
      • Kachaner I.
      • Kongnakorn T.
      • Durand-Zaleski I.
      Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin.
       Major bleeding$2518 (839)CIHI 2014 PCE−0.447 (0.149)Kaier and colleagues
      • Kaier K.
      • Gutmann A.
      • Baumbach H.
      • Zur Mühlen von C.
      • Hehn P.
      • Vach W.
      • et al.
      Quality of life among elderly patients undergoing transcatheter or surgical aortic valve replacement– a model-based longitudinal data analysis.
       Vascular injury$10,500 (3500)CIHI 2014 PCE−0.0463 (0.0154)Kaier and colleagues
      • Kaier K.
      • Gutmann A.
      • Baumbach H.
      • Zur Mühlen von C.
      • Hehn P.
      • Vach W.
      • et al.
      Quality of life among elderly patients undergoing transcatheter or surgical aortic valve replacement– a model-based longitudinal data analysis.
       Acute kidney injury$7450 (2483)CIHI 2014 PCE−0.177 (0.059)Kaier and colleagues
      • Kaier K.
      • Gutmann A.
      • Baumbach H.
      • Zur Mühlen von C.
      • Hehn P.
      • Vach W.
      • et al.
      Quality of life among elderly patients undergoing transcatheter or surgical aortic valve replacement– a model-based longitudinal data analysis.
       Atrial fibrillation$4704 (1568)CIHI 2014 PCE−0.0377 (0.01257)Kaier and colleagues
      • Kaier K.
      • Gutmann A.
      • Baumbach H.
      • Zur Mühlen von C.
      • Hehn P.
      • Vach W.
      • et al.
      Quality of life among elderly patients undergoing transcatheter or surgical aortic valve replacement– a model-based longitudinal data analysis.
       Nondisabling stroke$3815 (1272)CIHI 2014 PCE−0.161 (0.0537)Kaier and colleagues
      • Kaier K.
      • Gutmann A.
      • Baumbach H.
      • Zur Mühlen von C.
      • Hehn P.
      • Vach W.
      • et al.
      Quality of life among elderly patients undergoing transcatheter or surgical aortic valve replacement– a model-based longitudinal data analysis.
      All values are reported in Canadian dollars, 2016. When unavailable, standard deviations were derived as one third of the mean value per Saw and colleagues.
      • Saw J.
      • Bennell M.C.
      • Singh S.M.
      • Wijeysundera H.C.
      Cost-effectiveness of left atrial appendage closure for stroke prevention in atrial fibrillation patients with contraindications to anticoagulation.
      SD, Standard deviation; SAVR, surgical aortic valve replacement; NA, not applicable; TAVI, transcatheter aortic valve implantation; CIHI, Canadian Institute for Health Information; PCE, Patient Cost Estimator.
      Average of “average of hemorrhagic event” and “ischemic event of CNS” in Ontario.
      Transition into disabling stroke was assigned only transition costs because it is a long-term state and disutility is captured in utility assigned to disabling stroke state.

       Utilities and quality of life inputs

      Quality of life (QoL) utilities for the different health states were obtained from the literature given the absence of specific QoL data from the PARTNER 2 trial (Table 2).
      • Kaier K.
      • Gutmann A.
      • Baumbach H.
      • Zur Mühlen von C.
      • Hehn P.
      • Vach W.
      • et al.
      Quality of life among elderly patients undergoing transcatheter or surgical aortic valve replacement– a model-based longitudinal data analysis.
      • Lanitis T.
      • Cotté F.E.
      • Gaudin A.F.
      • Kachaner I.
      • Kongnakorn T.
      • Durand-Zaleski I.
      Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin.
      • Tengs T.O.
      • Lin T.H.
      A meta-analysis of quality-of-life estimates for stroke.
      • Lee A.J.
      • Morgan C.L.
      • Conway P.
      • Currie C.J.
      Characterisation and comparison of health-related quality of life for patients with renal failure.
      • Ambrosy A.P.
      • Hernandez A.F.
      • Armstrong P.W.
      • Butler J.
      • Dunning A.
      • Ezekowitz J.A.
      • et al.
      The clinical course of health status and association with outcomes in patients hospitalized for heart failure: insights from ASCEND-HF.
      • Reynolds M.R.
      • Magnuson E.A.
      • Wang K.
      • Thourani V.H.
      • Williams M.
      • Zajarias A.
      • et al.
      Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis.
      We used published EuroQol data from the PARTNER 1A trial
      • Reynolds M.R.
      • Magnuson E.A.
      • Wang K.
      • Thourani V.H.
      • Williams M.
      • Zajarias A.
      • et al.
      Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis.
      as a surrogate for baseline, 6-month, and 1-year utilities in the alive/well state in our model. Utilities for long-term Markov states were estimated from the literature for hospitalization,
      • Ambrosy A.P.
      • Hernandez A.F.
      • Armstrong P.W.
      • Butler J.
      • Dunning A.
      • Ezekowitz J.A.
      • et al.
      The clinical course of health status and association with outcomes in patients hospitalized for heart failure: insights from ASCEND-HF.
      dialysis,
      • Lee A.J.
      • Morgan C.L.
      • Conway P.
      • Currie C.J.
      Characterisation and comparison of health-related quality of life for patients with renal failure.
      and disabling stroke.
      • Tengs T.O.
      • Lin T.H.
      A meta-analysis of quality-of-life estimates for stroke.
      For periprocedural complications, we assigned a 1-time decrement in utility (ie, disutility), which represented a decreased QoL for that particular complication. These disutilities were estimated from a prospective observational cohort study of TAVI and SAVR cases published in the literature for major bleeding, vascular complications, acute kidney injury, atrial fibrillation, and nondisabling stroke.
      • Kaier K.
      • Gutmann A.
      • Baumbach H.
      • Zur Mühlen von C.
      • Hehn P.
      • Vach W.
      • et al.
      Quality of life among elderly patients undergoing transcatheter or surgical aortic valve replacement– a model-based longitudinal data analysis.
      The disutility for hospitalization was estimated from a French cost-effectiveness model of patients with atrial fibrillation.
      • Lanitis T.
      • Cotté F.E.
      • Gaudin A.F.
      • Kachaner I.
      • Kongnakorn T.
      • Durand-Zaleski I.
      Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin.

       Base-case and sensitivity analyses

      The base case was conducted fully probabilistically, with 10,000 Monte-Carlo simulations. All inputs described were sampled from distributions, with the expected value being the mean from the studies and the standard deviations from the source literature. For any data without standard deviations, we used one third of the point estimate as the standard deviation, as previously described.
      • Saw J.
      • Bennell M.C.
      • Singh S.M.
      • Wijeysundera H.C.
      Cost-effectiveness of left atrial appendage closure for stroke prevention in atrial fibrillation patients with contraindications to anticoagulation.
      For all probabilities and utilities, a beta distribution was used, whereas a gamma distribution was used for costs, procedural length, and hospital length of stay. The average costs and effects for the 10,000 simulations were used to calculate the base-case results and ICER. Parameter uncertainty was represented by a cost-effectiveness acceptability curve, showing the proportion of the simulations that favored TAVI at different willingness-to-pay (WTP) thresholds.
      A series of deterministic 1-way sensitivity analyses were also performed to examine the impact of key parameters in the model on the ICER. For probabilities, 95% confidence intervals were derived, and the lower and upper boundaries were used as the low and high values in the deterministic 1-way SA. For costs, the lower and upper values were ±50% of the estimated costs. In addition to the base-case analysis ICER, we performed a scenario analysis restricted to the transfemoral-access only cohort compared with the SAVR cohort (n = 775 in both groups). Efficacy inputs were informed from the periprocedural, 1-year, and 2-year event rates from the transfemoral access and SAVR group from the PARTNER 2 Trial.
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.

      Results

      In the base-case analysis, the index hospitalization cost in the TAVI group was $40,274 compared with $29,856 in the SAVR group. With 1.5% global discounting, the total lifetime cost was $46,904 ± $4038 and $36,356 ± $7309 in the TAVI and SAVR groups, respectively. The life-years gained were 7.57 ± 0.10 and 7.42 ± 0.11 for TAVI and SAVR, respectively. When QoL was taken into account, the QALYs gained were 5.63 ± 1.47 and 5.40 ± 1.47 for TAVI and SAVR, respectively (Table 3). Thus, the incremental cost was $10,547 and the incremental gain in QALY was 0.23. This resulted in an ICER of $46,083/QALY after discounting.
      Table 3Results of base-case analysis
      Treatment armTotal costTotal effectiveness (QALYs)Incremental cost/incremental effectivenessICER
      Discounted costs and QALYs
       TAVI$46,904 ± 40385.63 ± 1.47$10,547/0.23$46,083/QALY
       SAVR$36,356 ± 73095.40 ± 1.47
      Undiscounted costs and QALYs
       TAVI$47,054 ± 41136.18 ± 1.60$10,576/0.27$39,661/QALY
       SAVR$36,478 ± 72615.92 ± 1.63
      QALY, Quality-adjusted life-years; ICER, incremental cost-effectiveness ratio; TAVI, transcatheter aortic valve implantation; SAVR, surgical aortic valve replacement.
      The total undiscounted lifetime costs were $47,054 ± $4113 and $36,478 ± 7261 for TAVI and SAVR, respectively, for a difference in total costs of $10,576. The total undiscounted QALYs gained for TAVI and SAVR were 6.18 ± 1.60 and 5.92 ± 1.63, respectively, resulting in a difference of 0.27 QALYs. Thus, the ICER without discounting was $39,661/QALY.
      In 1-way sensitivity analyses, costs and procedural complication rate thresholds were calculated for a WTP of $50,000/QALY gained. The ICER exceeded $50,000/QALY gained when the cost of the TAVI valve system was greater than $25,100 (compared with base case of $24,000) or when TAVI ICU length of stay was greater than 2.3 days (base case of 2 days). For procedural complications, the ICER was greater than $50,000/QALY when the rate of periprocedural mortality in the TAVI was greater than 4.2% or less than 3.6% in the SAVR arm and the rate of periprocedural stroke in the SAVR was less than 5.5% and greater than 6.0% in the TAVI arm (base-case complication rates shown in Table E1). The results of the probabilistic analysis indicated that approximately 52.7% and 55.4% of the 10,000 iterations fell below the $50,000 and $100,000 per QALY gained WTP threshold when TAVI was compared with SAVR, respectively. The cost-effectiveness acceptability curve for TAVI versus SAVR, with a WTP threshold of $0 to $200,000, is shown in Figure 2.
      Figure thumbnail gr2
      Figure 2Cost-effectiveness acceptability curve for TAVI versus SAVR. The percent iterations of ICERs from the probabilistic analysis over the range of WTP from $0 to $200,000 are shown. CE, Cost-effectiveness; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation.
      In the transfemoral access scenario analysis, the index hospitalization cost was $40,210 in the transfemoral TAVI arm and $29,632 in the SAVR arm, and lifetime costs were $46,129 ± $4161 and $36,314 ± 7435, respectively. The QALYs gained was 5.84 ± 1.53 and 5.44 ± 1.48 in TAVI and SAVR, respectively, yielding a difference of 0.40 gained for TAVI. The ICER, when restricted to the comparison of transfemoral TAVI to SAVR, was $24,790/QALY.

      Discussion

      In this cost-utility analysis based on contemporary evidence, we have shown that TAVI may be cost-effective in comparison with SAVR in the intermediate surgical risk population with a favorable ICER of $46,083/QALY gained. This builds on numerous previous studies that have established that TAVI is an economically attractive option in the high surgical risk or the inoperable population.
      • Sud M.
      • Tam D.Y.
      • Wijeysundera H.C.
      The economics of transcatheter valve interventions.
      However, there was moderate-to-high uncertainty in our analyses, with the cost-effectiveness particularly sensitive to the cost of the TAVI prosthesis and the length of ICU stay.
      TAVI is a Class IIa recommendation for the intermediate-risk population with severe AS in the most recent American Heart Association guidelines (2017).
      • Nishimura R.A.
      • Otto C.M.
      • Bonow R.O.
      • Carabello B.A.
      • Erwin J.P.
      • Fleisher L.A.
      • et al.
      2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      The intermediate surgical risk population represents a different population compared with the inoperable and high surgical risk population because these patients have substantially less comorbidities.
      • Leon M.B.
      • Smith C.R.
      • Mack M.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • et al.
      Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.
      • Smith C.R.
      • Leon M.B.
      • Mack M.J.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • et al.
      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
      As such, their derived benefit from TAVI and associated costs differ. There is only 1 other study that compared costs in the intermediate-risk population using propensity score matching of 42 pairs of patients at a single Dutch institution.
      • Osnabrugge R.L.J.
      • Head S.J.
      • Genders T.S.S.
      • Van Mieghem N.M.
      • de Jaegere P.P.T.
      • van der Boon R.M.A.
      • et al.
      Costs of transcatheter versus surgical aortic valve replacement in intermediate-risk patients.
      In this study, Osnabrugge and colleagues
      • Osnabrugge R.L.J.
      • Head S.J.
      • Genders T.S.S.
      • Van Mieghem N.M.
      • de Jaegere P.P.T.
      • van der Boon R.M.A.
      • et al.
      Costs of transcatheter versus surgical aortic valve replacement in intermediate-risk patients.
      found that initial in-hospital costs were higher in TAVI compared with the SAVR population (€40,802 vs €33,354; P = .010) and higher at 1-year follow-up (total cost: €46,217 vs €35,511; P = .009). The study did not consider effectiveness, but simply compared the costs of the interventions in a small sample of patients from a single institution over a 1-year time horizon. In contrast, our study used the recently published PARTNER 2 multicenter RCT data with more than 2000 patients to determine costs and effectiveness in a Markov model over a lifetime time horizon. Similar to the study by Osnabrugge and colleagues,
      • Osnabrugge R.L.J.
      • Head S.J.
      • Genders T.S.S.
      • Van Mieghem N.M.
      • de Jaegere P.P.T.
      • van der Boon R.M.A.
      • et al.
      Costs of transcatheter versus surgical aortic valve replacement in intermediate-risk patients.
      our overall in-hospital costs at 30 days and lifetime follow-up costs were higher in the TAVI group compared with the SAVR group. Although costs were higher in the TAVI groups, the patients also accrued more QALYs over the lifetime horizon compared with SAVR in the base-case analysis. The cost findings of this study were similar to those reported by Wijeysundera and colleagues,
      • Wijeysundera H.C.
      • Li L.
      • Braga V.
      • Pazhaniappan N.
      • Pardhan A.M.
      • Lian D.
      • et al.
      Drivers of healthcare costs associated with the episode of care for surgical aortic valve replacement versus transcatheter aortic valve implantation.
      who used micro-costing data from Ontario hospitals (TAVI, $42,742; interquartile range, $37,295-$56,196 vs SAVR, $21,811; interquartile range, $18,148-$30,498).
      • Wijeysundera H.C.
      • Li L.
      • Braga V.
      • Pazhaniappan N.
      • Pardhan A.M.
      • Lian D.
      • et al.
      Drivers of healthcare costs associated with the episode of care for surgical aortic valve replacement versus transcatheter aortic valve implantation.
      Consistent with previous studies,
      • Doble B.
      • Blackhouse G.
      • Goeree R.
      • Xie F.
      Cost-effectiveness of the Edwards SAPIEN transcatheter heart valve compared with standard management and surgical aortic valve replacement in patients with severe symptomatic aortic stenosis: a Canadian perspective.
      • Wijeysundera H.C.
      • Li L.
      • Braga V.
      • Pazhaniappan N.
      • Pardhan A.M.
      • Lian D.
      • et al.
      Drivers of healthcare costs associated with the episode of care for surgical aortic valve replacement versus transcatheter aortic valve implantation.
      our study found that the major cost-drivers were the cost of the TAVI prosthesis (TAVI vs SAVR: $24,000 vs ∼$6000 CAD), rates of complications, and length of stay in the ICU in our sensitivity analysis. Of note, TAVI was no longer cost-effective when the TAVI valve system cost was increased by $1100 or when ICU LOS increased by 0.3 days. This highlights the impact of parameter uncertainty on the base-case results and the importance of conducting a fully probabilistic analysis such that all point estimates are drawn from specific distributions to address uncertainty. Nonetheless, our findings suggest that cost-savings through reduced ICU and hospital LOS help offset the higher acquisition cost of the TAVI valve system. In addition, the sensitivity of our analyses to these parameters reinforces the need for early discharge algorithms for patients undergoing TAVI to optimize length of stay, as well as increased market competition to reduce acquisitions costs for the prostheses themselves.
      • Lauck S.B.
      • Wood D.A.
      • Baumbusch J.
      • Kwon J.-Y.
      • Stub D.
      • Achtem L.
      • et al.
      Vancouver transcatheter aortic valve replacement clinical pathway: minimalist approach, standardized care, and discharge criteria to reduce length of stay.
      The American College of Cardiology and American Heart Association consider a WTP threshold of greater than 3 times a country's gross domestic product (GDP) to be of low value, whereas a threshold between 1 and 3 times GDP is of intermediate value and less than a country's GDP to be high value.
      • Anderson J.L.
      • Heidenreich P.A.
      • Barnett P.G.
      • Creager M.A.
      • Fonarow G.C.
      • Gibbons R.J.
      • et al.
      ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines.
      Thus, in both the Canadian and American perspective, ICERS less than $50,000/QALY represent high value and ICERs between $50,000 and $150,000/QALY represent intermediate value. Although the base-case analysis of our study would suggest that TAVI is a cost-effective alternative compared with SAVR in the intermediate-risk population, our probabilistic sensitivity analysis showed that TAVI was the preferred option in only 52.6% of simulations when the WTP threshold was $50,000/QALY gained (Figure 2). There was variation in terms of effectiveness and the ICER was inferior to SAVR in 41.7% of cases, representing moderate-to-high uncertainty around efficacy point estimates and the noninferiority nature of the results. Moreover, as highlighted earlier, even relatively small changes in the cost of the TAVI prosthesis or length of stay will have substantial impact on the overall cost-effectiveness. This underscores the limited evidence base in the intermediate-risk population and reinforces the need for additional clinical trials in this area.
      Consistent with findings in the literature, the ICER in our scenario analysis of a transfemoral only cohort was lower than that of the entire cohort (transfemoral and transapical access) when compared with SAVR.
      • Reynolds M.R.
      • Magnuson E.A.
      • Lei Y.
      • Wang K.
      • Vilain K.
      • Li H.
      • et al.
      Cost-effectiveness of transcatheter aortic valve replacement compared with surgical aortic valve replacement in high-risk patients with severe aortic stenosis: results of the PARTNER (Placement of Aortic Transcatheter Valves) trial (Cohort A).
      The literature has shown lower index procedural and hospitalization costs along with improved outcomes in the transfemoral group compared with the transapical cohort.
      • Wijeysundera H.C.
      • Li L.
      • Braga V.
      • Pazhaniappan N.
      • Pardhan A.M.
      • Lian D.
      • et al.
      Drivers of healthcare costs associated with the episode of care for surgical aortic valve replacement versus transcatheter aortic valve implantation.
      This difference likely is reflective of the older and more comorbid nature of the transapical cohort along with the less-invasiveness nature of transfemoral TAVI. Nonetheless, this reaffirms that transfemoral TAVI remains the preferred choice for access when possible. However, these results should be interpreted in the context of the design of the PARTNER 2 trial: The primary outcome was for the entire cohort, and secondary analyses considered stratifying by route of access.
      The FDA has approved TAVI in the intermediate surgical risk population based on findings from the PARTNER 2 Trial. The intermediate-risk population already represents a substantial proportion of patients with severe AS treated with TAVI, accounting for 40% of patients in an analysis of the STS Transcatheter Valve Therapy database.
      • Holmes D.R.
      • Nishimura R.A.
      • Grover F.L.
      • Brindis R.G.
      • Carroll J.D.
      • Edwards F.H.
      • et al.
      Annual outcomes with transcatheter valve therapy: from the STS/ACC TVT Registry.
      Moreover, ongoing RCTs (NCT02825134, NCT02675114) are being conducted in the low-risk population (STS <4%). Multiple European registries have shown that TAVI has comparable results to SAVR in this even lower-risk population,
      • Rosato S.
      • Santini F.
      • Barbanti M.
      • Biancari F.
      • D'Errigo P.
      • Onorati F.
      • et al.
      Transcatheter aortic valve implantation compared with surgical aortic valve replacement in low-risk patients.
      • Frerker C.
      • Bestehorn K.
      • Schlüter M.
      • Bestehorn M.
      • Hamm C.W.
      • Möllmann H.
      • et al.
      In-hospital mortality in propensity-score matched low-risk patients undergoing routine isolated surgical or transfemoral transcatheter aortic valve replacement in 2014 in Germany.
      representing another emerging group that may be eligible for TAVI in the near future. As the demand for TAVI increases, there are important implications for adapting existing infrastructure for care delivery. For example, accommodating increased TAVI use may require a shift in hospital priorities as greater capacity is needed for hybrid operating rooms or catheterization laboratories. A shift in human resources also may be needed as staff require additional training to perform these specialized procedures. These additional resources are typically not incorporated into a cost-utility analysis, but nonetheless are critical considerations.

       Study Limitations

      The interpretation of the results of our cost-utility analysis must be taken in the context of some limitations that merit discussion. Derivation of the initial procedural costs for SAVR and TAVI was obtained from expert opinion and thus may not be generalizable to other jurisdictions. Regardless, the rigor in costing data in the current study is confirmed because reported procedural costs were similar to previously published work from Ontario using micro-costing data.
      • Wijeysundera H.C.
      • Li L.
      • Braga V.
      • Pazhaniappan N.
      • Pardhan A.M.
      • Lian D.
      • et al.
      Drivers of healthcare costs associated with the episode of care for surgical aortic valve replacement versus transcatheter aortic valve implantation.
      Nonetheless, we acknowledge that the cost of medical care in the United States is substantially higher than that of the Canadian health care system. Although the costs may be higher in the US setting, they will likely be higher in both the TAVI and SAVR arms, so the incremental cost, and therefore ICER, would remain similar. Point estimates may vary slightly because of different cost inputs, but we do not expect a directional change. Furthermore, there was uncertainty around utility inputs in our study because the PARTNER 2 trial has yet to publish their utility study. However, the data we used from the PARTNER 1A trial of high-risk patients followed a similar pattern observed in other studies published in the literature, with patients in the TAVI group showing an earlier and more rapid improvement in QoL within the first 3 months of the procedure.
      • Reynolds M.R.
      • Magnuson E.A.
      • Wang K.
      • Thourani V.H.
      • Williams M.
      • Zajarias A.
      • et al.
      Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis.

      Cohen DJ. Health status benefits of transcatheter vs surgical aortic valve replacement in patients with severe aortic stenosis at intermediate surgical risk. Presented at: TCT 20167; November 1, 2016; Washington, DC. Available at: https://www.acc.org/˜/media/Clinical/PDF-Files/Approved-PDFs/2016/10/25/07/TCT16_Nov01/950amET%20PARTNER%20II%20QUALITY%20OF%20LIFE.pdf. Accessed February 6, 2018.

      A major limitation of our model is that the TAVI valve durability remains uncertain in the intermediate-risk population because the study only followed patients to 2 years. Currently, the best evidence to support valve durability is derived from the PARTNER 1A trial; there were no cases of structural valve deterioration at 5 years.
      • Mack M.J.
      • Leon M.B.
      • Smith C.R.
      • Miller D.C.
      • Moses J.W.
      • Tuzcu E.M.
      5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial.
      Although patients in PARTNER 1A were older (mean age, 83.6-84.5 years) than patients in PARTNER 2 (mean age, 81.5-81.7 years), the average life years gained in our model was 7 years.
      • Smith C.R.
      • Leon M.B.
      • Mack M.J.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • et al.
      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
      Thus, we thought that valve durability would be similar to surgery over the lifetime of these octogenarians. However, extended follow-up of these patients will be of critical importance for low-risk young patients as TAVI indications evolve. Furthermore, findings from this study are generalizable to the intermediate-risk population only. The low-risk population may present with their own efficacy rates, complication rates, and length of stay that may affect the overall cost-effectiveness of TAVI. Last, PARTNER II only provided outcomes to 2 years; thus, after 2 years, we estimated the rate of mortality from Canadian life tables and assumed that these patients had a similar life expectancy to Canadians of similar age and gender. This methodology is consistent with previously published cost-effectiveness analyses. Furthermore, work by Mihaljevic and colleagues
      • Mihaljevic T.
      • Nowicki E.R.
      • Rajeswaran J.
      • Blackstone E.H.
      • Lagazzi L.
      • Thomas J.
      • et al.
      Survival after valve replacement for aortic stenosis: implications for decision making.
      showed that life expectancy is restored to that of age- and gender-matched controls in patients aged more than 65 years undergoing aortic valve replacement for AS.

      Conclusions

      From the perspective of the Canadian health care system, compared with SAVR, TAVI may be a cost-effective option for the treatment of severe AS in the intermediate surgical risk population with an ICER of $46,083/QALY in the base-case analysis. However, there was moderate to high uncertainty in our parameter estimates; only 52.7% and 55.4% of the ICERS in our simulations were below the WTP thresholds of $50,000 and $100,000/QALY, respectively. This meant that 44.6% to 47.3% of cases were not cost-effective. As such, despite the potential patient preference for a less-invasive approach, before widespread expansion of TAVI indications to lower-risk patients, more rigorous clinical evidence is needed.

       Conflict of Interest Statement

      H.C.W. has received research funding from Edwards Lifesciences and Medtronic Inc. S.E.F. serves as a proctor for Medtronic Inc. All other authors have nothing to disclose with regard to commercial support.

      Appendix

      Table E1Base-case analysis efficacy inputs
      VariableTAVISAVRSource
      ProportionAlphaBetaProportionAlphaBeta
      Perioperative events (<30 d)
       Death0.039399720.04041980Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Any stroke0.054559560.06061960Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Disabling stroke
      The rate of patients of disabling stroke in patients with any stroke.
      0.58232230.7054318Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Any renal failure0.013139980.03031990Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Dialysis
      Rate of patients with acute kidney injury who required subsequent dialysis postprocedure obtained from PARTNER 1A.
      0.7141040.714104Smith and colleagues (2011)
      • Smith C.R.
      • Leon M.B.
      • Mack M.J.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • et al.
      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
       Vascular injury0.079809310.05051970Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Major bleeding0.1041059060.433442579Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Atrial fibrillation0.090919200.260265756Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Hospitalization0.064649470.06162959Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
      Long-term events (year 1)
       Death0.086848880.08583897Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Any stroke0.024239330.01918942Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Disabling stroke
      The rate of patients of disabling stroke in patients with any stroke.
      0.7081770.684136Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Any renal failure0.019199790.01717973Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Dialysis0.7141040.714104Smith and colleagues (2011)
      • Smith C.R.
      • Leon M.B.
      • Mack M.J.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • et al.
      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
       Hospitalization0.082788690.07673886Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Death on dialysis0.53568590.5356859Brennan and colleagues (2012)
       Any stroke on dialysis0.071227729,7880.071227729,788Foley and colleagues (2011)
      • Foley R.N.
      • Gilbertson D.T.
      • Murray T.
      • Collins A.J.
      Long interdialytic interval and mortality among patients receiving hemodialysis.
       Disabling stroke0.0771120.077112Maeda and colleagues (2015)
       Death related to stroke0.410170124480.41017012448Brønnum-Hansen and colleagues (2001)
      • Brønnum-Hansen H.
      • Davidsen M.
      • Thorvaldsen P.
      Danish MONICA Study Group. Long-term survival and causes of death after stroke.
       Rehospitalization0.125152510,6570.125152510,657Holmes and colleagues (2015)
      • Holmes D.R.
      • Nishimura R.A.
      • Grover F.L.
      • Brindis R.G.
      • Carroll J.D.
      • Edwards F.H.
      • et al.
      Annual outcomes with transcatheter valve therapy: from the STS/ACC TVT Registry.
      Long-term events (year 2)
       Death0.048438450.05146851Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Any stroke0.014139200.0066936Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Disabling stroke
      The rate of patients of disabling stroke in patients with any stroke.
      0.7691030.62553Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Any renal failure0.00449750.0099964Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Dialysis
      Rate of patients with acute kidney injury who required subsequent dialysis postprocedure obtained from PARTNER 1A.
      0.7141040.714104Smith and colleagues (2011)
      • Smith C.R.
      • Leon M.B.
      • Mack M.J.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • et al.
      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
       Hospitalization0.047418280.02421865Leon and colleagues (2016)
      • Leon M.B.
      • Smith C.R.
      • Mack M.J.
      • Makkar R.R.
      • Svensson L.G.
      • Kodali S.K.
      • et al.
      Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.
       Death on dialysis0.53568590.5356859Brennan and colleagues (2012)
      • Brennan J.M.
      • Edwards F.H.
      • Zhao Y.
      • O'Brien S.M.
      • Douglas P.S.
      • Peterson E.D.
      • et al.
      Long-term survival after aortic valve replacement among high-risk elderly patients in the United States: insights from the Society of Thoracic Surgeons Adult Cardiac Surgery Database, 1991 to 2007.
       Any stroke on dialysis0.071227729,7880.071227729,788Foley and colleagues (2011)
      • Foley R.N.
      • Gilbertson D.T.
      • Murray T.
      • Collins A.J.
      Long interdialytic interval and mortality among patients receiving hemodialysis.
       Disabling stroke0.0771120.077112Maeda and colleagues (2015)
      • Maeda K.
      • Kuratani T.
      • Torikai K.
      • Ichibori Y.
      • Nakatani K.
      • Onishi T.
      • et al.
      Early outcomes in Japanese dialysis patients treated with transcatheter aortic valve implantation.
       Hospitalization during dialysis0.45814,68517,3800.45814,68517,380Foley and colleagues (2011)
      • Foley R.N.
      • Gilbertson D.T.
      • Murray T.
      • Collins A.J.
      Long interdialytic interval and mortality among patients receiving hemodialysis.
       Death related to stroke0.410170124480.41017012448Brønnum-Hansen and colleagues (2001)
      • Brønnum-Hansen H.
      • Davidsen M.
      • Thorvaldsen P.
      Danish MONICA Study Group. Long-term survival and causes of death after stroke.
       Rehospitalization0.125152510,6570.125152510,657Holmes and colleagues (2015)
      • Holmes D.R.
      • Nishimura R.A.
      • Grover F.L.
      • Brindis R.G.
      • Carroll J.D.
      • Edwards F.H.
      • et al.
      Annual outcomes with transcatheter valve therapy: from the STS/ACC TVT Registry.
      Alpha and beta shape parameters were derived from event rates in the TAVI and SAVR arms as previously described by Doble and colleagues (2013). TAVI, Transcatheter aortic valve implantation; SAVR, surgical aortic valve replacement.
      The rate of patients of disabling stroke in patients with any stroke.
      Rate of patients with acute kidney injury who required subsequent dialysis postprocedure obtained from PARTNER 1A.

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      Linked Article

      • Aortic valve implantation or replacement: Which procedure is more cost-effective?
        The Journal of Thoracic and Cardiovascular SurgeryVol. 156Issue 5
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          Cost-effectiveness analysis of a procedure is always difficult because of the many factors involved and the quantification of costs to achieve the desired outcome. In particular, the new devices for transcatheter aortic valve implantation (TAVI) are increasingly compared with traditional prostheses, not only in terms of clinical outcome but also in terms of costs, because of the more expensive technology required.1
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