Economic Value of Transcatheter Valve Replacement for Inoperable Aortic Stenosis

ABSTRACT

Objectives: To project the social value of transcatheter aortic valve replacement (TAVR) for inoperable patients with severe, symptomatic aortic stenosis (SSAS).

Study Design: This study used an economic model with parameters obtained from the literature and from US Census Bureau population projections.

Methods: Our model estimated the economic value that will accrue to inoperable patients with SSAS and to device manufacturers as a result of TAVR utilization. We estimated individual patient value as the monetized gain in quality-adjusted life-years as estimated in the cost-effectiveness literature, net of device costs and cost offsets. We estimated manufacturer value by applying an assumed profit margin to revenue from device sales. We created population-level estimates by combining these individual-level estimates with age-stratified Census Bureau population projections and estimates of the incidence of AS. We assessed model uncertainty through the use of probabilistic sensitivity analyses.

Results: Between 2018 and 2028, approximately 465,000 inoperable Americans with SSAS will be treated with TAVR. These procedures will yield a cumulative social benefit of up to $48 billion, with roughly 80% of that benefit accruing to patients and 20% accruing to device manufacturers.

Conclusions: Policy makers and payers should take this social value into account when considering decisions related to the care of inoperable patients with SSAS.

Am J Manag Care. 2020;26(2):e50-e56. https://doi.org/10.37765/ajmc.2020.42401

Takeaway Points

Considering the US population between 2018 and 2028, we estimated the annual and cumulative social value accruing to patients and to manufacturers as a result of uptake of transcatheter aortic valve replacement (TAVR) for the treatment of severe, symptomatic aortic stenosis (SSAS) in inoperable patients.

• In 2018, approximately 39,000 inoperable patients with SSAS were treated with TAVR in the United States.
• That number is projected to increase as the population ages and as TAVR uptake grows.
• TAVR treatment of the inoperable population with SSAS will generate approximately $48 billion in social value between 2018 and 2028, with 80% of that value accruing to patients.

Aortic stenosis (AS) is a common disease, affecting 2% to 7% of the global population older than 65 years.¹ Although the condition can be asymptomatic for years, when symptoms do appear, untreated patients with severe AS have high mortality (up to 50% within 2 years).^2,3 Surgical aortic valve replacement (SAVR), in which the sternum is opened to replace the aortic valve, has been shown to improve survival and quality of life in patients with severe, symptomatic AS (SSAS).^4,5 Despite data supporting the use of SAVR for the treatment of SSAS, at least 30% of patients do not undergo SAVR, because of either patient preference to avoid invasive surgery or ineligibility for surgery as a result of advanced age and associated comorbidities (the latter referred to as inoperable patients).^6,7 Historically, this population of untreated patients was treated with medical management alone, resulting in 3-year mortality rates as high as 80%.^8,9 Transcatheter aortic valve replacement (TAVR) is a less invasive method of AVR in which the aortic valve is replaced through either the femoral artery or a small incision in the chest. Clinical trial data have demonstrated that TAVR for inoperable patients extends median survival by approximately 19 months and significantly improves quality of life compared with medical therapy alone,^10,11 thereby offering an alternative treatment for this patient population. Accordingly, TAVR was first approved for commercialization in Europe in 2007¹² and by the US FDA in 2011 for the treatment of SSAS in inoperable patients.

With commercial approval of TAVR, the volume of these procedures in the United States has grown dramatically. Within Medicare, TAVR grew from 8.9% of all AVR procedures (across all risk groups) in 2012 to 50.3% in 2017.¹³ This rapid growth suggests a need for an analysis of the aggregate economic impact of TAVR treatment on the distribution of social welfare for inoperable patients; this type of study is referred to as social value analysis.¹⁴ These types of studies provide a useful complement to traditional cost-effectiveness analyses, as they incorporate the value to consumers, as well as the value to innovators, allowing policy makers to consider new technologies in a context that is both broad and deep. Inoperable patients who are treated with TAVR realize benefits in the form of increased quantity and quality of life relative to medical management. In addition, firms that manufacture TAVR devices realize benefits by way of profits earned on units sold. Payers may realize both costs (eg, via incremental new spending on TAVR devices) and benefits (eg, cost offsets realized through the avoidance of downstream events, such as postoperative inpatient readmissions). Assessing the value of TAVR to both payers and manufacturers allows for the estimation of the relative share of economic surplus returning to manufacturers (as opposed to consumers), therefore informing a broader discussion regarding optimal incentives for future innovation.

The purpose of this study was to estimate the present and future economic impact of TAVR adoption for inoperable patients with SSAS and for TAVR device manufacturers in the United States, using recently developed approaches for the assessment of economic value.^15-20 Using an analysis time frame of 2018 to 2028, we aimed to project the size of the inoperable population with SSAS, estimate the fraction of this population who will receive TAVR, and calculate the economic returns of that utilization, for both the patients and the device manufacturers.

METHODS

Projecting TAVR-Eligible Population From 2018 to 2028

To estimate the future economic impact of TAVR adoption for patients with inoperable SSAS and for TAVR manufacturers, we began by projecting the size of the inoperable population eligible for TAVR treatment.

To determine the number of inoperable patients with SSAS between 2018 and 2028, we first projected the number of patients with SSAS nationally, regardless of surgical risk status. We did this by multiplying current estimates of severe AS incidence rates (stratified by age) by the proportion of patients with severe AS whose disease is symptomatic,^21,22 and then multiplying the resulting quantity by age-stratified US population projections for each year in the analysis period.²³ Finally, we multiplied the values described earlier by the estimated fraction of patients with SSAS considered inoperable.⁷ The parameters used to perform these calculations are presented in Table 1.^{7,21,22,24-26}

Projecting TAVR Utilization From 2018 to 2028

Only a fraction of incident inoperable SSAS cases are treated with TAVR.^21,27 As such, we estimated the number of inoperable patients using TAVR in the future as the product of (1) the projected eligible inoperable population in each year (described previously), and (2) an estimate of the fraction of eligible inoperable patients who ultimately receive TAVR, extracted from the literature.²¹ As a conservative assumption, we assumed that this fraction remains constant over time. We also assumed that individuals can receive the treatment only once.

Calculation of Industry Value

TAVR market share estimates were available for the population with SSAS but not specifically for the inoperable population with SSAS. In addition, the prices of the different TAVR devices for the different SSAS risk groups (inoperable, high risk, and intermediate risk) are very similar.²⁴ As such, for the purposes of this analysis, we used the best peer-reviewed cost-effectiveness evidence available, without regard to TAVR device type, and assumed that these results applied to all inoperable patients treated with TAVR.²⁵ Cost-effectiveness results were then employed to calculate patient value (discussed later). As most contemporary TAVR procedures are performed using transfemoral (TF) access, we used cost-effectiveness results from a TF cohort.

We calculated industry revenue by multiplying the device price by the number of TAVR procedures on inoperable patients projected to occur annually between 2018 and 2028. We assumed that device cost would remain constant across years (Table 1^{7,21,22,24-26}).²⁵ In addition, we conservatively assumed profit—analogous to welfare gains in the context of social value analysis—to be 80% of revenue.²⁸ This is substantially larger than the profit margins of 18% to 29% reported by device manufacturers in recent years.^29,30 Formally, (undiscounted) industry value in year t was calculated as N_t × P × p, where N_t denotes the number of procedures, P denotes the device price, and p denotes the profit margin.

Computation of the Monetized QALY Benefit of TAVR

We estimated the monetized value of the quality-adjusted life-year (QALY) gain for each treated inoperable patient by assuming a QALY willingness-to-pay (WTP) value of $150,000 (Table 1^{7,21,22,24-26}).^26,31 A threshold of $150,000 was chosen because incremental cost-effectiveness ratios (ICERs) above this cutoff are considered low economic value as defined by the American Heart Association and the American College of Cardiology.³² We estimated the total monetized QALY gain for the US inoperable SSAS population in each year as the product of the individual monetized QALY value and the number of TAVR procedures on inoperable patients in each year.

Calculation of Patient Value

To circumvent the complexities of the US insurance market, this analysis used a societal perspective to estimate patient value. In this framework, we computed the net value that an individual obtains from TAVR as the difference between the monetized valuation of the QALY benefit (described previously) and the incremental difference in costs, including differences in the device cost, as well as differences in postprocedural medical expenses. The concept of patient value is thus an amalgamation of value returning to the patient (in the form of improved quality and/or quantity of life) and the change in medical costs borne by payers, which may be either patients themselves or, more typically, commercial or government insurers. For convenience, we refer to this construct as patient value. We extracted the values for cost offsets (including device cost) from the literature (Table 1^{7,21,22,24-26})²⁵ and converted them to 2017 US$ using the Medical Consumer Price Index.³³ We assumed a discount rate of 3% consistent with US guidelines.³⁴ Formally, (undiscounted) patient value in year t was calculated as N_t × (Q × WTP — P — C), where N_t denotes the number of procedures, Q denotes the QALY gain of TAVR relative to medical management, WTP denotes the WTP value for a QALY, P denotes the device price, and C denotes the estimated cost offsets of TAVR relative to medical management.

Sensitivity and Scenario Analyses

We assessed the model’s sensitivity to the joint uncertainty of all input parameters by implementing a probabilistic sensitivity analysis (PSA). In a PSA, model results are iteratively regenerated following resampling of input parameters from assumed statistical distributions, which are derived from published or assumed values (eg, means and CIs) describing the uncertainty of parameter point estimates. We varied QALY gains, lifetime cost offsets, incidence rates, the proportion of severe AS that is symptomatic, the proportion of SSAS that is inoperable, and the proportion of inoperable patients with SSAS who receive TAVR. Table 1^{7,21,22,24-26} shows the assumed statistical distributions of the uncertainty parameters and assumptions that governed the PSA. We performed 1000 replications of the model and computed the fraction of these in which estimated societal value exceeded estimated industry value. We also separately present results from a scenario analysis, which uses a WTP value of $100,000 per QALY in place of the base-case parameter value of $150,000.

RESULTS

TAVR Uptake Projections

Between 2018 and 2028, approximately 465,000 Americans with inoperable SSAS were projected to receive TAVR. Because the gradual aging of the US population will slowly increase the annual incidence of SSAS, regardless of risk status, the number of inoperable patients with SSAS receiving TAVR was also projected to grow over time. Full projection results are presented in Table 2.

Annual Social Value

In 2018, approximately 39,000 inoperable patients with SSAS were estimated to receive TAVR, resulting in a cumulative gain of about 50,000 QALYs (Table 2). After accounting for device costs and cost offsets, and using a WTP value of $150,000 per QALY, approximately $3.7 billion in patient value was created. By contrast, assuming that firms retain 80% of revenues as profits, approximately $940 million of the social value accrued to manufacturers. When these values were projected to 2028, we estimated that these undiscounted benefits would increase to $4.4 billion and $1.1 million ($3.2 billion and $810 million discounted) in patient value and manufacturer value, respectively.

Cumulative Social Value

Between 2018 and 2028, we projected the total QALY gain among inoperable patients with SSAS to be 600,486 QALYs and the cumulative social value of TAVR (summing over inoperable patients and manufacturers) to be $48.1 billion. Roughly 80% of that value ($38.5 billion) accrued to patients and roughly 20% ($9.6 billion) to manufacturers (Table 2). Furthermore, we projected that the undiscounted social value will grow over time as the incidence of SSAS increases (Figure 1²¹).

Sensitivity and Scenario Analysis Results

Figure 2 depicts repeated simulations of the model results following joint draws from the statistical distributions that describe the uncertainty in each of the model parameters (shown in Table 1^{7,21,22,24-26}). The base-case (deterministic) result is indicated as a single light blue point; the results of each of the 1000 replications are represented as dark blue points. Points appearing above the orange line represent instances in which the value accruing to patients is greater than the value accruing to manufacturers, and points below it indicate the reverse. In 99.8% of the replicated simulations, the economic value to inoperable patients was greater than the economic value to manufacturers.

When the WTP for a QALY was assumed to be $100,000, the cumulative patient value was estimated to fall from $38.5 billion to $12.6 billion, and the estimated share of value accruing to manufacturers would rise from 20.0% to 43.3% (Table 3). When the PSA was conducted using this lower valuation, patient value exceeded manufacturer value in 67.8% of the simulations.

DISCUSSION

Our findings suggest that substantial social value will be created as a result of TAVR treatment for inoperable patients with SSAS over the next decade. Our study projected that up to $48.1 billion in value will be generated between 2018 and 2028, with roughly 80% of that value accruing to inoperable patients and 20% to manufacturers. A PSA suggested that the portion of social value realized by inoperable patients is likely to exceed the value that will return to manufacturers, as this result was obtained in up to 99.8% of the simulated repetitions.

Prior research has found that TAVR is cost-effective compared with medical management in the inoperable population. Using data from the PARTNER B trial (ClinicalTrials.gov NCT00530894), Reynolds et al found that TAVR would generate a lifetime benefit of 1.29 QALYs per patient, at an incremental cost of $79,837, resulting in an ICER of $50,212 per QALY.²⁵ Our study builds on these results by estimating the total social value that TAVR will generate and assessing the distribution of that value between patients and manufacturers. This perspective is useful for payers and policy makers because it extends the decision-making calculus around TAVR adoption beyond a narrow consideration of short-term costs. In addition, our study informs a larger debate in the literature regarding the relationship between the manufacturer share of economic returns from a new medical technology and incentives for future innovation.^35,36

Although we observed a large social benefit of TAVR in the inoperable population with SSAS, it is possible that we underestimated the true benefit. First, the data used to inform our study were derived from the use of a first-generation device in the early age of TAVR. Over the past 10 years, there have been substantial improvements in device technology, procedural planning, operator experience, and post-TAVR care, which have been associated with better clinical outcomes and lower resource utilization.^37-39 Another factor that may also contribute to underestimating the social benefit of TAVR in the inoperable population is the effect of prior undertreatment of this population on our future projection. Durko et al estimated that roughly one-third of inoperable patients with incident SSAS do not receive TAVR.²¹ This value aligns closely with our own comparison of the number of AVR procedures performed annually in the United States with our estimates of the number of annual incident cases (results not shown) and is consistent with previous research.⁴⁰ Furthermore, previous research has suggested that roughly a quarter of patients with SSAS who are offered only SAVR will decline it.⁴¹ Accordingly, it is unknown what fraction of patients who are eligible for TAVR either are not offered it or decline it, thereby leading to the undertreatment of this population. To the extent that patient perception of TAVR as a less invasive alternative grows over time, undertreatment of SSAS may be reduced.⁴² As such, the cost-effectiveness of TAVR in the current era may be greater than previously estimated, and thus our calculations may underestimate the true social value of TAVR in the inoperable population with SSAS.

It is useful to consider our results in the context of other social value studies. Although this study provides the first assessment of the distributional effects on social value for TAVR, informative comparisons are available in the literature. Our estimate of the share of value returning to manufacturers for TAVR (roughly 20%) is nearly identical to the fraction estimated by a recent study on statins.¹⁸ A much lower estimate (2%) was obtained for pediatric vaccines,²⁰ whereas another study found that between 25% and 66% of value accrues to manufacturers for 3 therapies treating multiple sclerosis, depending on modeling assumptions.⁴³ This context suggests that, relative to several therapies, TAVR may generate reasonably large returns to inoperable patients and to society per dollar of manufacturer profit.

Of note, TAVR has also been demonstrated to be cost-effective relative to SAVR for operable patients at high⁴⁴ and intermediate⁴⁵ surgical risk. Furthermore, recent clinical trials have demonstrated that TAVR yields substantial benefits relative to SAVR for patients at low surgical risk, who comprise the largest proportion of patients with SSAS.^46,47 This suggests, first, that the social value of TAVR may extend beyond the inoperable risk group and, second, that this value will be inherently conditional on the degree to which patients and doctors select treatment with TAVR or SAVR. Future research should address these questions directly.

Limitations

This study has several limitations. First, the results rely on projections of unknown future quantities (eg, the percentage of inoperable patients with SSAS who will receive TAVR). We sought to make realistic projections through analysis of data observed in the recent past. However, to the extent that our projections are inaccurate, our estimates may be biased. For example, we assumed the incidence of AS to remain constant, whereas real-world data show that the age-adjusted population incidence of AS decreased in recent years.⁴⁸ Second, we estimated base-case results by incorporating several parameters obtained from the literature into a single economic model. Many of these parameters were estimated with uncertainty, including the QALY benefit and cost offset associated with TAVR usage, as well as the fraction of patients with SSAS considered inoperable. We sought to mitigate this limitation by incorporating the uncertainty associated with each input parameter into a joint PSA. Additionally, as noted previously, the estimated benefit of TAVR for inoperable patients (1.29 QALYs) was obtained from a cost-effectiveness study of an early-generation TAVR device (SAPIEN), as these are the only data available for this patient population.²⁵ Because patient outcomes have improved over time and resource utilization has decreased, we may have underestimated the social value of TAVR by using this data. Third, the data that provided our QALY benefit and cost-offset input parameters considered only TAVR procedures conducted via the TF route²⁵ and did not consider TAVR procedures performed via the less common alternative access routes (eg, transapical). Thus, our results cannot be generalized to TAVR performed via alternative access in this population, although we believe that inoperable patients eligible only for alternative access represent a small portion of the overall population, given that the rates of alternative-access TAVR have decreased substantially over time because of the progressively smaller delivery system of newer-generation TAVR devices.⁴⁹ Finally, our estimate of the cost offsets associated with TAVR for inoperable patients comes from a study that used a 1-year period.²⁵ Thus, our model did not account for any cost differences that might exist beyond this period.

CONCLUSIONS

We sought to estimate the value that will accrue to society—both in aggregate and to different segments of society—as a result of expected TAVR uptake by inoperable patients with SSAS between 2018 and 2028. We projected that up to $48.1 billion in social value will be generated, with roughly 80% of that value accruing to patients and the remainder accruing to manufacturers. Future research is needed to assess the social value of TAVR in patients with operable SSAS.Author Affiliations: Precision Health Economics, Oakland (JS, TTS) and Los Angeles (EvE, ABJ), CA; Lahey Hospital and Medical Center (SJB), Burlington, MA; Edwards Lifesciences (CT, SC), Irvine, CA; Harvard Medical School (ABJ), Boston, MA; Massachusetts General Hospital (ABJ), Boston, MA.

Source of Funding: Edwards Lifesciences Inc.

Author Disclosures: Dr Sussell was an employee of Precision Health Economics, a consultancy of the health and life sciences industries, at the time of this study. Ms van Eijndhoven and Mr Schwartz are employees of Precision Health Economics. Dr Baron reports consulting for Edwards Lifesciences, advisory board membership for Abiomed and Boston Scientific Corp, and a pending research grant from Boston Scientific Corp. Dr Thompson and Mr Clancy are full-time employees of and own stock in Edwards Lifesciences, which manufactures transcatheter aortic valve implants. Dr Jena has received consulting fees unrelated to this work from Pfizer, Bristol-Myers Squibb, Novartis, Amgen, Eli Lilly, Vertex Pharmaceuticals, AstraZeneca, Celgene, Tesaro, Sanofi Aventis, Biogen, and Precision Health Economics and has received consulting fees for economic expert testimony from Analysis Group.

Authorship Information: Concept and design (JS, EvE, TTS, SJB, CT, SC, ABJ); acquisition of data (JS, EvE, TTS, SC); analysis and interpretation of data (JS, EvE, TTS, SJB, CT, SC, ABJ); drafting of the manuscript (JS, EvE, TTS, SJB, SC, ABJ); critical revision of the manuscript for important intellectual content (JS, EvE, TTS, SJB, CT, SC, ABJ); statistical analysis (JS, EvE, ABJ); provision of patients or study materials (CT, SC); obtaining funding (SC); administrative, technical, or logistic support (TTS, CT, SC); and supervision (JS, CT, SC, ABJ).

Address Correspondence to: Emma van Eijndhoven, MS, MA, Precision Health Economics, 11100 Santa Monica Blvd, Ste 500, Los Angeles, CA 90025. Email: emma.vaneijndhoven@precisionhealtheconomics.com.REFERENCES

1. Vahanian A, Alfieri O, Andreotti F, et al; Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012;33(19):2451-2496. doi: 10.1093/eurheartj/ehs109.

2. Turina J, Hess O, Sepulcri F, Krayenbuehl H. Spontaneous course of aortic valve disease. Eur Heart J. 1987;8(5):471-483. doi: 10.1093/oxfordjournals.eurheartj.a062307.

3. Kelly TA, Rothbart RM, Cooper CM, Kaiser DL, Smucker ML, Gibson RS. Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis. Am J Cardiol. 1988;61(1):123-130. doi: 10.1016/0002-9149(88)91317-3.

4. Murphy ES, Lawson RM, Starr A, Rahimtoola SH. Severe aortic stenosis in patients 60 years of age or older: left ventricular function and 10-year survival after valve replacement. Circulation. 1981;64(2, pt 2):II184-II188.

5. Schwarz F, Baumann P, Manthey J, et al. The effect of aortic valve replacement on survival. Circulation. 1982;66(5):1105-1110. doi: 10.1161/01.cir.66.5.1105.

6. Varadarajan P, Kapoor N, Bansal RC, Pai RG. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg. 2006;82(6):2111-2115. doi: 10.1016/j.athoracsur.2006.07.048.

7. Iung B, Cachier A, Baron G, et al. Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery? Eur Heart J. 2005;26(24):2714-2720. doi: 10.1093/eurheartj/ehi471.

8. Kapadia SR, Tuzcu EM, Makkar RR, et al. Long-term outcomes of inoperable patients with aortic stenosis randomly assigned to transcatheter aortic valve replacement or standard therapy. Circulation. 2014;130(17):1483-1492. doi: 10.1161/CIRCULATIONAHA.114.009834.

9. Herrmann HC, Thourani VH, Kodali SK, et al; PARTNER Investigators. One-year clinical outcomes with SAPIEN 3 transcatheter aortic valve replacement in high-risk and inoperable patients with severe aortic stenosis. Circulation. 2016;134(2):130-140. doi: 10.1161/CIRCULATIONAHA.116.022797.

10. Kapadia SR, Leon MB, Makkar RR, et al; PARTNER Trial Investigators. 5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet. 2015;385(9986):2485-2491. doi: 10.1016/S0140-6736(15)60290-2.

11. Reynolds MR, Magnuson EA, Lei Y, et al; Placement of Aortic Transcatheter Valves (PARTNER) Investigators. Health-related quality of life after transcatheter aortic valve replacement in inoperable patients with severe aortic stenosis. Circulation. 2011;124(18):1964-1972. doi: 10.1161/CIRCULATIONAHA.111.040022.

12. Dvir D, Barbash IM, Ben-Dor I, et al. The development of transcatheter aortic valve replacement in the USA. Arch Cardiovasc Dis. 2012;105(3):160-164. doi: 10.1016/j.acvd.2012.02.003.

13. MEDPAR Limited Data Set (LDS) — hospital (national). CMS website. cms.gov/Research-Statistics-Data-and-Systems/Files-for-Order/LimitedDataSets/MEDPARLDSHospitalNational. Updated August 19, 2019. Accessed January 15, 2020.

14. Michaud PC, Goldman DP, Lakdawalla DN, Zheng Y, Gailey AH. The value of medical and pharmaceutical interventions for reducing obesity. J Health Econ. 2012;31(4):630-643. doi: 10.1016/j.jhealeco.2012.04.006.

15. Goldman DP, Jena AB, Lakdawalla DN, Malin JL, Malkin JD, Sun E. The value of specialty oncology drugs. Health Serv Res. 2010;45(1):115-132. doi: 10.1111/j.1475-6773.2009.01059.x.

16. Lakdawalla DN, Sun EC, Jena AB, Reyes CM, Goldman DP, Philipson TJ. An economic evaluation of the war on cancer. J Health Econ. 2010;29(3):333-346. doi: 10.1016/j.jhealeco.2010.02.006.

17. Philipson TJ, Jena AB. Who benefits from new medical technologies? estimates of consumer and producer surpluses for HIV/AIDS drugs. Forum Health Econ Policy. 2006;9(2). doi: 10.2202/1558-9544.1005.

18. Grabowski DC, Lakdawalla DN, Goldman DP, et al. The large social value resulting from use of statins warrants steps to improve adherence and broaden treatment. Health Aff (Millwood). 2012;31(10):2276-2285. doi: 10.1377/hlthaff.2011.1120.

19. Yin W, Penrod JR, Maclean R, Lakdawalla DN, Philipson T. Value of survival gains in chronic myeloid leukemia. Am J Manag Care. 2012;18(suppl 11):S257-S264.

20. Philipson TJ, Thornton Snider J, Chit A, et al. The social value of childhood vaccination in the United States. Am J Manag Care. 2017;23(1):41-47.

21. Durko AP, Osnabrugge RL, Van Mieghem NM, et al. Annual number of candidates for transcatheter aortic valve implantation per country: current estimates and future projections. Eur Heart J. 2018;39(28):2635-2642. doi: 10.1093/eurheartj/ehy107.

22. Benjamin EJ, Blaha MJ, Chiuve SE, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146-e603. doi: 10.1161/CIR.0000000000000485.

23. Cohen DJ, Breall JA, Ho KK, et al. Economics of elective coronary revascularization: comparison of costs and charges for conventional angioplasty, directional atherectomy, stenting and bypass surgery. J Am Coll Cardiol. 1993;22(4):1052-1059. doi: 10.1016/0735-1097(93)90415-w

24. Pricing — supply & implant. ECRI Institute website. ecri.org/components/PriceGuideDB/Pages/default.aspx. Accessed December 11, 2018.

25. Reynolds MR, Magnuson EA, Wang K, et al; PARTNER Investigators. Cost-effectiveness of transcatheter aortic valve replacement compared with standard care among inoperable patients with severe aortic stenosis: results from the placement of aortic transcatheter valves (PARTNER) trial (cohort B). Circulation. 2012;125(9):1102-1109. doi: 10.1161/CIRCULATIONAHA.111.054072.

26. Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796-797. doi: 10.1056/NEJMp1405158.

27. Osnabrugge RL, Mylotte D, Head SJ, et al. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol. 2013;62(11):1002-1012. doi: 10.1016/j.jacc.2013.05.015.

28. Caves RE, Whinston MD, Hurwitz MA. Patent expiration, entry, and competition in the U.S. pharmaceutical industry. Brookings Pap Econ Act Microecon. 1991;22(1991):1-66.

29. Edwards Lifesciences 2017 annual report. Edwards Lifesciences website. ir.edwards.com/static-files/cd27c9df-fb38-44dd-a1fc-82f2c5f1aa36. Accessed January 15, 2019.

30. Annual report: fiscal year 2018. Medtronic website. newsroom.medtronic.com/static-files/262eb1cb-ed16-422c-b33c-d9f031105481. Accessed January 15, 2019.

31. Viscusi WK, Aldy JE. The value of a statistical life: a critical review of market estimates throughout the world. J Risk Uncertain. 2003;27(1):5-76.

32. Anderson JL, Heidenreich PA, Barnett PG, et al; ACC/AHA Task Force on Performance Measures; ACC/AHA Task Force on Practice Guidelines. 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. Circulation. 2014;129(22):2329-2345. doi: 10.1161/CIR.0000000000000042.

33. Consumer price index for all urban consumers: medical care in U.S. city average. Federal Reserve Bank of St. Louis website. fred.stlouisfed.org/series/CPIMEDSL. Accessed October 17, 2018.

34. Sanders GD, Neumann PJ, Basu A, et al. Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: Second Panel on Cost-Effectiveness in Health and Medicine [erratum in JAMA. 2016;316(18):1924]. JAMA. 2016;316(10):1093-1103. doi: 10.1001/jama.2016.12195.

35. Loury GC. Market structure and innovation. Q J Econ. 1979;93(3):395-410. doi: 10.2307/1883165.

36. Nordhaus WD. An economic theory of technological change. Am Econ Rev. 1969;59(2):18-28.

37. Arnold S, Lei Y, Reynolds M, et al; PARTNER Investigators. Costs of periprocedural complications in patients treated with transcatheter aortic valve replacement: results from the Placement of Aortic Transcatheter Valve trial. Circ Cardiovasc Interv. 2014;7(6):829-836. doi: 10.1161/CIRCINTERVENTIONS.114.001395.

38. Babaliaros V, Devireddy C, Lerakis S, et al. Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysis. JACC Cardiovascular Interv. 2014;7(8):898-904. doi: 10.1016/j.jcin.2014.04.005.

39. Lauck SB, Wood DA, Baumbusch J, et al. Vancouver transcatheter aortic valve replacement clinical pathway: minimalist approach, standardized care, and discharge criteria to reduce length of stay. Circ Cardiovasc Qual Outcomes. 2016;9(3):312-321. doi: 10.1161/CIRCOUTCOMES.115.002541.

40. Hahn RT, Kodali S, Généreux P, Leon M. Paravalvular regurgitation following transcutaneous aortic valve replacement: predictors and clinical significance. Curr Cardiol Rep. 2014;16(5):475. doi: 10.1007/s11886-014-0475-6.

41. Charlson E, Legedza AT, Hamel MB. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis. 2006;15(3):312-321.

42. Malaisrie SC, Tuday E, Lapin B, et al. Transcatheter aortic valve implantation decreases the rate of unoperated aortic stenosis. Eur J Cardiothorac Surg. 2011;40(1):43-48. doi: 10.1016/j.ejcts.2010.11.031.

43. Shih T, Wakeford C, Meletiche D, et al. Reconsidering the economic value of multiple sclerosis therapies. Am J Manag Care. 2016;22(11):e368-e374.

44. Reynolds MR, Lei Y, Wang K, et al; CoreValve US High Risk Pivotal Trial Investigators. Cost-effectiveness of transcatheter aortic valve replacement with a self-expanding prosthesis versus surgical aortic valve replacement. J Am Coll Cardiol. 2016;67(1):29-38. doi: 10.1016/j.jacc.2015.10.046.

45. Baron SJ, Wang K, House JA, et al. Cost-effectiveness of transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at intermediate risk. Circulation. 2019;139(7):877-888. doi: 10.1161/CIRCULATIONAHA.118.035236.

46. Mack MJ, Leon MB, Thourani VH, et al; PARTNER 3 Investigators. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med. 2019;380(18):1695-1705. doi: 10.1056/NEJMoa1814052.

47. Popma JJ, Deeb GM, Yakubov SJ, et al; Evolut Low Risk Trial Investigators. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med. 2019;380(18):1706-1715. doi: 10.1056/NEJMoa1816885.

48. Bonow RO, Greenland P. Population-wide trends in aortic stenosis incidence and outcomes. Circulation. 2015;131(11):969-971. doi: 10.1161/CIRCULATIONAHA.115.014846.

49. Grover FL, Vemulapalli S, Carroll JD, et al; STS/ACC TVT Registry. 2016 annual report of The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. J Am Coll Cardiol. 2017;69(10):1215-1230. doi: 10.1016/j.jacc.2016.11.033.

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