Cost-effectiveness analysis of transcatheter aortic valve implantation in aortic stenosis patients at low- and intermediate-surgical risk in Japan.

OBJECTIVE: To analyze the cost-effectiveness of transcatheter aortic valve implantation (TAVI) using the SAPIEN 3 (Edwards Lifesciences, Irvine, CA) compared to surgical aortic valve replacement (SAVR) in low- and intermediate-risk patients from a Japanese public healthcare payer perspective. METHODS: A Markov model cost-effectiveness analysis was developed. Clinical and utility data were extracted from a systematic literature review. Cost inputs were obtained from analysis of the Medical Data Vision claims database and supplemented with a targeted literature search. The robustness of the results was assessed using sensitivity analyses. Scenario analyses were performed to determine the impact of lower mean age (77.5 years) and the effect of two different long-term mortality hazard ratios (TAVI versus SAVR: 0.9-1.09) on both risk-level populations. This analysis was conducted according to the guidelines for cost-effectiveness evaluation in Japan from Core 2 Health. RESULTS: In intermediate-risk patients, TAVI was a dominant procedure (TAVI had lower cost and higher effectiveness). In low-risk patients, the incremental cost effectiveness ratio (ICER) for TAVI was ¥750,417/quality-adjusted-life-years (QALY), which was below the cost-effectiveness threshold of ¥5 million/QALY. The ICER for TAVI was robust to all tested sensitivity and scenario analyses. CONCLUSIONS: TAVI was dominant and cost-effective compared to SAVR in intermediate- and low-risk patients, respectively. These results suggest that TAVI can provide meaningful value to Japanese patients relative to SAVR, at a reasonable incremental cost for patients at low surgical risk and potentially resulting in cost-savings in patients at intermediate surgical risk.

Aortic Stenosis (AS) is the most common valvular heart disease in Japan, and, if left untreated, severe symptomatic AS (sSAS) is associated with a dramatic increase in mortality and morbidity. Transcatheter Aortic Valve Implantation (TAVI) is a minimally invasive treatment option for replacing the aortic valve in patients with sSAS and has been associated with similar or better outcomes compared to Surgical Aortic Valve Replacement (SAVR), which involves open-heart surgical replacement of the aortic valve. The objective of this study was to compare the costs and health outcomes associated with TAVI compared to SAVR in Japanese patients deemed low- or intermediate-risk for surgery. Despite the expanding use of TAVI in Japan, a cost-effectiveness analysis (CEA) does not exist that evaluates the economics of TAVI with the current generation SAPIEN 3 implant in patients with low- and intermediate-risk from a public perspective. Our study suggests that TAVI represents strong value for money among low- and intermediate-risk patients in Japan: compared to SAVR, TAVI is associated with better clinical outcomes and quality of life for patients, at a reasonable additional cost for low-risk patients and at a lower cost for intermediate-risk patients.

Aortic valve replacement today: Outcomes, costs, and opportunities for improvement.

The introduction of transcatheter aortic valve replacement (TAVR) just two decades ago has transformed the treatment of severe symptomatic aortic stenosis. TAVR has not only extended the option of aortic valve replacement to patients deemed ineligible for surgery, it has also demonstrated similar or better short- and intermediate-term clinical outcomes compared with surgical aortic valve replacement (SAVR) in patients at all levels of surgical risk. These benefits have been achieved with similar or lower costs compared with SAVR, at least in the first 1-2 years for intermediate- and low-risk patients. Longer-term data will further inform clinical and shared decision-making. SUMMARY FOR ANNOTATED TABLE OF CONTENTS: In just over two decades, transcatheter aortic valve replacement has emerged as a frontline approach for appropriately selected patients with severe aortic stenosis. A growing body of evidence documents similar or better clinical outcomes and cost-effectiveness for transcatheter compared with surgical aortic valve replacement. Whether the mode is transcatheter or surgical, aortic valve replacement remains underutilized in patients with clear indications for intervention.

Long-term risk of reintervention after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has surpassed surgical aortic valve replacement (SAVR) as the predominant mode of valve replacement for the treatment of severe aortic stenosis (AS). However, the long-term need for valvular reintervention after TAVR remains unknown. METHODS: Using data from the Medicare Fee for Service 100% dataset, all patients receiving TAVR between July 2011 and December 2020 were identified. Patients were categorized as receiving a valve reintervention (either surgical or transcatheter) or not using the appropriate International Classification of Diseases 10th Revision Procedure Coding System (ICD-10-PCS). A competing risk regression model was used to estimate the cumulative probability of valve reintervention. RESULTS: Of 230,644 TAVR patients were identified, of whom 1,880 received a reintervention. Patients receiving a reintervention were younger and more likely to be male. At 10 years, the crude rate of reintervention was 0.59% within a surviving cohort of 341 patients. After adjusting for the competing risk of death and other covariates, the adjusted cumulative incidence of reintervention at 10 years after TAVR was 1.63%. When the rate of reinterventions was compared between early (2011-2016) and later (2017-2020) time periods, the risk-adjusted rate of reintervention at 4 years had decreased over time (0.85% vs 0.51%). CONCLUSION: The 10-year risk of valve reintervention after TAVR is low and appears to be decreasing over time. Further research is necessary to determine the driving factors contributing to valve reintervention in the current era.

Days at Home After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients.

BACKGROUND: Days at home (DAH) represents an important patient-oriented outcome that quantifies time spent at home after a medical event; however, this outcome has not been fully evaluated for low-surgical-risk patients undergoing transcatheter aortic valve replacement (TAVR). We sought to compare 1- and 2-year DAH (DAH365 and DAH730) among low-risk patients participating in a randomized trial of TAVR with a self-expanding bioprosthesis versus surgical aortic valve replacement (SAVR). METHODS: Using Medicare-linked data from the Evolut Low Risk trial, we identified 619 patients: 606 (322 TAVR/284 SAVR) and 593 (312 TAVR/281 SAVR) were analyzed at 1 and 2 years, respectively. DAH was calculated as days alive and spent outside a hospital, inpatient rehabilitation, skilled nursing facility, long-term acute care hospital, emergency department, or observation stay. Mean DAH was compared using the t test. RESULTS: The mean (SD) age and female sex were 74.7 (5.1) and 74.3 (4.9) years and 34.6% (115/332) and 30.3% (87/287) in TAVR and SAVR, respectively. Postprocedural discharge to rehabilitation occurred in ≤3.0% (≤10/332) in TAVR and 4.5% (13/287) in SAVR. The mean DAH365 was comparable in TAVR versus SAVR (352.2±45.4 versus 347.8±39.0; difference in days, 4.5 [95% CI, 2.3-11.2]; P=0.20). DAH730 was also comparable in TAVR versus SAVR (701.6±106.0 versus 699.6±94.5; difference in days, 2.0 [-14.1 to 18.2]; P=0.81). Secondary outcomes DAH30 and DAH90 were higher in TAVR (DAH30, 26.0±3.6 versus 20.7±6.4; difference in days, 5.3 [4.5-6.2]; P<0.001; DAH90, 85.1±8.3 versus 78.7±13.6; difference in days, 6.4 [4.6-8.2]; P<0.001). CONCLUSIONS: In the Evolut Low Risk trial linked to Medicare, low-risk patients undergoing TAVR spend a similar number of days at home at 1 and 2 years compared with SAVR. Days spent at home at 30 and 90 days were higher in TAVR. In contrast to higher-risk patients studied in prior work, there is no clear advantage of TAVR versus SAVR for DAH in the first 2 years after AVR in low-surgical-risk patients.

Utilization Trends In Platelet Adenosine Diphosphate P2Y12 Receptor Inhibitor and Cost Among Medicare Beneficiaries.

Recent guidelines regarding acute coronary syndrome (ACS) have advocated for use of prasugrel and ticagrelor over clopidogrel for acute coronary syndrome. However, analyses from multiple databases have shown that clopidogrel continues to be the most commonly prescribed P2Y12 inhibitor. We aimed to evaluate the trends in utilization and cost of P2Y12 inhibitors for Medicare beneficiaries using data from Medicare Part D Prescription Drug Data Event set from 2011 to 2018 for P2Y12 inhibitors. Medicare part D total beneficiaries for P2Y12 receptor inhibitors increased from 2011 to 2018 by 34.8% from 2.45 million to 3.31 million. The total cost for P2Y12 antiplatelets decreased from $ 3.72 billion in 2011 to $ 0.72 billion in 2018 by 80.4%. The availability of generic clopidogrel drove the considerable total cost reduction. Clopidogrel was the most prescribed P2Y12 inhibitor since its introduction accounting for more than 90% of the Medicare beneficiaries from 2013 to 2018. Overall, the number of beneficiaries on newer P2Y12 inhibitors showed a steady increase with 5.9% beneficiaries on brilinta in 2018 and 2.1 % on prasugrel. The total cost of brilinta beneficiaries grew exponentially accounting for 59.2% of total cost in 2018 and average cost per beneficiary increased by 465% in study period. Despite the availability of generic version clopidogrel and prasugrel, 2,161,175 beneficiaries were on brand plavix and 87,174 on effient which contributed to the increased total expenditure. Earlier introduction and transition to generic versions of medication may help to reduce the drug cost and potentially enhance medication compliance.

Days at home after transcatheter or surgical aortic valve replacement in high-risk patients.

BACKGROUND: Days at home (DAH) quantifies time spent at home after a medical event but has not been fully evaluated for TAVR. We sought to compare 1- and 5-year DAH (DAH365, DAH1825) among high-risk patients participating in a randomized trial of transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis versus surgical aortic valve replacement (SAVR). METHODS: We linked data from the U.S. CoreValve High Risk Trial to Medicare Fee-for-Service claims in 456 patients with 450 (234 TAVR/216 SAVR) and 427 (222 TAVR/205 SAVR) analyzed at 1 and 5 years. DAH was calculated as the number of days alive and spent outside of a hospital, skilled nursing facility, rehabilitation, long-term acute care hospital, emergency department, or observation stay. RESULTS: Mean DAH365 was higher in patients who underwent TAVR compared with SAVR (295.1 ± 106.9 vs 267.8 ± 122.3, difference in days 27.2 [95% CI 6.0, 48.5], P = .01). Compared with SAVR, TAVR patients had a shorter index length of stay (LOS) (7.4 ± 4.5 vs 12.5 ± 9.0, difference in days -5.1 [-6.5, -3.8], P < .001). The largest contributions to decreased DAH365 were mortality days and total facility days after discharge from the index hospitalization (mortality days-TAVR: 34.7 ± 93.1 vs SAVR: 48.0 ± 108.8, difference in days -13.3 [95% CI -32.1, 5.5], P = .17; total facility days-TAVR: 27.9 ± 47.4 vs SAVR: 36.7 ± 48.9, difference in days -8.8 [95% CI -17.8, 0.1], P = .05). Mean DAH1825 was numerically but not statistically significantly higher in TAVR (TAVR: 1154.2 ± 659.0 vs SAVR: 1067.6 ± 697.3, difference in days 86.6 [95% CI -42.3, 215.6], P = .19). Landmark analysis showed no difference in DAH from years 1 to 5 (TAVR: 1040.4 ± 477.5 vs SAVR: 1022.9 ± 489.3, P = .74). CONCLUSIONS: In the U.S. CoreValve High Risk Trial linked to Medicare, high-risk patients undergoing TAVR spend an average of 27 additional DAH compared with SAVR in the first year after the procedure due to a shorter index LOS and the additive effect of fewer but nonsignificantly different mortality and total facility days after discharge from the index hospitalization compared with SAVR. After the first year, both groups spend a similar number of DAH. These results describe the postprocedural course of high-risk patients from a patient-centered perspective, which may guide expectations regarding longitudinal health care needs and inform shared decision-making.

Outcomes of stroke events during transcatheter aortic valve implantation.

BACKGROUND: Despite improvements in the safety of transcatheter aortic valve implantation (TAVI), ~4% of patients experience a procedure-related stroke. Understanding long-term health and healthcare implications of these events may motivate the development and adoption of preventative strategies.  Aims: We aimed to assess the association of TAVI-related ischaemic stroke with subsequent clinical outcomes and healthcare utilisation. METHODS: We used Medicare fee-for-service claims to identify patients who underwent their first TAVI between January 2012 and December 2017. Previously used ICD-9-CM and ICD-10-CM codes were used to identify TAVI-related ischaemic stroke. Among those with and without TAVI-related ischaemic stroke, we compared the risk of a composite endpoint that included all-cause mortality, acute myocardial infarction, and subsequent stroke using inverse probability treatment weighted Cox regression. We also performed a difference-in-difference analysis to compare 1-year Medicare expenditures and days spent at home during the first year after TAVI. RESULTS:  Among 129,628 primary TAVI patients, 5,549 (4.3%) had a procedure-related stroke. These patients were more likely to be female and have had prior stroke, peripheral vascular disease, ischaemic heart disease, or renal failure. After adjustment, TAVI-related ischaemic stroke was associated with a higher risk of the 1-year composite outcome (HR 1.67, 95% CI: 1.56-1.78), higher 1-year Medicare expenditures (difference $9,245 [standard error 790], p<0.001), and fewer days at home during the first year (difference 16 days [standard error 1], p<0.001). CONCLUSIONS: Among Medicare beneficiaries undergoing TAVI, procedure-related ischaemic stroke was associated with worse outcomes, increased Medicare expenditures, and less time spent at home. Procedure-related ischaemic stroke during TAVI remains a critically important and potentially preventable source of patient mortality, morbidity and healthcare utilisation.

Contemporary Costs Associated With Transcatheter Versus Surgical Aortic Valve Replacement in Medicare Beneficiaries.

BACKGROUND: In patients with severe aortic stenosis, treatment with transcatheter aortic valve replacement (TAVR) has been shown to be cost-effective in the high-risk surgical population and cost-saving in the intermediate-risk population when compared with surgical aortic valve replacement (SAVR) in early pivotal clinical trials. Whether TAVR is associated with comparable or lower costs when compared with SAVR in contemporary clinical practice is unknown. METHODS: Using data from the Medicare Dataset Standard Analytic Files 5% Fee for Service database, patients receiving either TAVR or SAVR between 2016 and 2018 were identified. Patients were categorized as low, intermediate, or high mortality risk based on 2 validated indices-the Hospital Frailty Risk Score and the logEuroScore. Health care costs out to 1 year were compared between TAVR and SAVR among the low, intermediate, and high-risk groups, after adjustment for patient demographics. RESULTS: Nine thousand seven hundred forty-six patients were identified (4834 TAVR; 3760 SAVR) and included in the analysis. Patients receiving TAVR were older and more likely to be female. Index hospitalization costs were significantly lower with TAVR compared with SAVR across all risk strata (logEuroScore: low: $61 845 versus $68 986; intermediate: $64 658 versus $76 965; high: $65 594 versus $91 005; P<0.001 for all). Follow-up costs through 1 year were generally lower with TAVR and this difference was more pronounced in the low risk groups (logEuroScore: $9763 versus $14 073; Hospital Frailty Risk Score: $10 116 versus $12 880). Accordingly, cumulative 1-year costs were substantially lower with TAVR compared with SAVR. CONCLUSIONS: At 1 year, TAVR is associated with lower health care costs across all risk strata when compared with SAVR in contemporary practice. If long-term data continue to demonstrate similar clinical outcomes and valve durability with TAVR and SAVR, these findings suggest that TAVR may be the preferred treatment strategy for patients with aortic stenosis from an economic standpoint.

Racial, Ethnic, and Socioeconomic Disparities in Access to Transcatheter Aortic Valve Replacement Within Major Metropolitan Areas.

Importance: Despite the benefits of high-technology therapeutics, inequitable access to these technologies may generate disparities in care. Objective: To examine the association between zip code-level racial, ethnic, and socioeconomic composition and rates of transcatheter aortic valve replacement (TAVR) among Medicare patients living within large metropolitan areas with TAVR programs. Design, Setting, and Participants: This multicenter, nationwide cross-sectional analysis of Medicare claims data between January 1, 2012, and December 31, 2018, included beneficiaries of fee-for-service Medicare who were 66 years or older living in the 25 largest metropolitan core-based statistical areas. Exposure: Receipt of TAVR. Main Outcomes and Measures: The association between zip code-level racial, ethnic, and socioeconomic composition and rates of TAVR per 100 000 Medicare beneficiaries. Results: Within the studied metropolitan areas, there were 7590 individual zip codes. The mean (SD) age of Medicare beneficiaries within these areas was 71.4 (2.0) years, a mean (SD) of 47.6% (5.8%) of beneficiaries were men, and a mean (SD) of 4.0% (7.0%) were Asian, 11.1% (18.9%) were Black, 8.0% (12.9%) were Hispanic, and 73.8% (24.9%) were White. The mean number of TAVRs per 100 000 Medicare beneficiaries by zip code was 249 (IQR, 0-429). For each $1000 decrease in median household income, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.2% (95% CI, 0.1%-0.4%) lower (P = .002). For each 1% increase in the proportion of patients who were dually eligible for Medicaid services, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 2.1% (95% CI, 1.3%-2.9%) lower (P < .001). For each 1-unit increase in the Distressed Communities Index score, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.4% (95% CI, 0.2%-0.5%) lower (P < .001). Rates of TAVR were lower in zip codes with higher proportions of patients of Black race and Hispanic ethnicity, despite adjusting for socioeconomic markers, age, and clinical comorbidities. Conclusions and Relevance: Within major metropolitan areas in the US with TAVR programs, zip codes with higher proportions of Black and Hispanic patients and those with greater socioeconomic disadvantages had lower rates of TAVR, adjusting for age and clinical comorbidities. Whether this reflects a different burden of symptomatic aortic stenosis by race and socioeconomic status or disparities in use of TAVR requires further study.

Socioeconomic and Geographic Characteristics of Hospitals Establishing Transcatheter Aortic Valve Replacement Programs, 2012-2018.

BACKGROUND: Despite the benefits of novel therapeutics, inequitable diffusion of new technologies may generate disparities. We examined the growth of transcatheter aortic valve replacement (TAVR) in the United States to understand the characteristics of hospitals that developed TAVR programs and the socioeconomic status of patients these hospitals served. METHODS: We identified fee-for-service Medicare beneficiaries aged 66 years or older who underwent TAVR between January 1, 2012, and December 31, 2018, and hospitals that developed TAVR programs (defined as performing ≥10 TAVRs over the study period). We used linear regression models to compare socioeconomic characteristics of patients treated at hospitals that did and did not establish TAVR programs and described the association between core-based statistical area level markers of socioeconomic status and TAVR rates. RESULTS: Between 2012 and 2018, 583 hospitals developed new TAVR programs, including 572 (98.1%) in metropolitan areas, and 293 (50.3%) in metropolitan areas with preexisting TAVR programs. Compared with hospitals that did not start TAVR programs, hospitals that did start TAVR programs treated fewer patients with dual eligibility for Medicaid (difference of -2.83% [95% CI, -3.78% to -1.89%], P≤0.01), higher median household incomes (difference $2447 [95% CI, $1348-$3547], P=0.03), and from areas with lower distressed communities index scores (difference -4.02 units [95% CI, -5.43 to -2.61], P≤0.01). After adjusting for the age, clinical comorbidities, race and ethnicity and socioeconomic status, areas with TAVR programs had higher rates of TAVR and TAVR rates per 100 000 Medicare beneficiaries were higher in core-based statistical areas with fewer dual eligible patients, higher median income, and lower distressed communities index scores. CONCLUSIONS: During the initial growth phase of TAVR programs in the United States, hospitals serving wealthier patients were more likely to start programs. This pattern of growth has led to inequities in the dispersion of TAVR, with lower rates in poorer communities.

Temporal Changes in Mortality After Transcatheter and Surgical Aortic Valve Replacement: Retrospective Analysis of US Medicare Patients (2012-2019).

Background The treatment of aortic stenosis is evolving rapidly. Pace of change in the care of patients undergoing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) differs. We sought to determine differences in temporal changes in 30-day mortality, 30-day readmission, and length of stay after TAVR and SAVR. Methods and Results We conducted a retrospective cohort study of patients treated in the United States between 2012 and 2019 using data from the Medicare Data Set Analytic File 100% Fee for Service database. We included consecutive patients enrolled in Medicare Parts A and B and aged ≥65 years who had SAVR or transfemoral TAVR. We defined 3 study cohorts, including all SAVR, isolated SAVR (without concomitant procedures), and elective isolated SAVR and TAVR. The primary end point was 30-day mortality; secondary end points were 30-day readmission and length of stay. Statistical models controlled for patient demographics, frailty measured by the Hospital Frailty Risk Score, and comorbidities measured by the Elixhauser Comorbidity Index (ECI). Cox proportional hazard models were developed with TAVR versus SAVR as the main covariates with a 2-way interaction term with index year. We repeated these analyses restricted to full aortic valve replacement hospitals offering both SAVR and TAVR. The main study cohort included 245 269 patients with SAVR and 188 580 patients with TAVR, with mean±SD ages 74.3±6.0 years and 80.7±6.9 years, respectively, and 36.5% and 46.2% female patients, respectively. Patients with TAVR had higher ECI scores (6.4±3.6 versus 4.4±3) and were more frail (55.4% versus 33.5%). Total aortic valve replacement volumes increased 61% during the 7-year span; TAVR volumes surpassed SAVR in 2017. The magnitude of mortality benefit associated with TAVR increased until 2016 in the main cohort (2012: hazard ratio [HR], 0.76 [95% CI, 0.67-0.86]; 2016: HR, 0.39 [95% CI, 0.36-0.43]); although TAVR continued to have lower mortality rates from 2017 to 2019, the magnitude of benefit over SAVR was attenuated. A similar pattern was seen with readmission, with a lower risk of readmission from 2012 to 2016 for patients with TAVR (2012: HR, 0.68 [95% CI, 0.63-0.73]; 2016: HR, 0.43 [95% CI, 0.41-0.45]) followed by a lesser difference from 2017 to 2019. Year over year, TAVR was associated with increasingly shorter lengths of stay compared with SAVR (2012: HR, 1.91 [95% CI, 1.84-1.98]; 2019: HR, 5.34 [95% CI, 5.22-5.45]). These results were consistent in full aortic valve replacement hospitals. Conclusions The rate of improvement in TAVR outpaced SAVR until 2016, with the recent presence of U-shaped phenomena suggesting a narrowing gap between outcomes. Future longitudinal research is needed to determine the long-term implications of lowering risk profiles across treatment options to guide case selection and clinical care.

Economic value of transcatheter valve replacement for inoperable aortic stenosis.

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.

Cost-Effectiveness of Tafamidis Therapy for Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: In patients with transthyretin amyloid cardiomyopathy, tafamidis reduces all-cause mortality and cardiovascular hospitalizations and slows decline in quality of life compared with placebo. In May 2019, tafamidis received expedited approval from the US Food and Drug Administration as a breakthrough drug for a rare disease. However, at $225 000 per year, it is the most expensive cardiovascular drug ever launched in the United States, and its long-term cost-effectiveness and budget impact are uncertain. We therefore aimed to estimate the cost-effectiveness of tafamidis and its potential effect on US health care spending. METHODS: We developed a Markov model of patients with wild-type or variant transthyretin amyloid cardiomyopathy and heart failure (mean age, 74.5 years) using inputs from the ATTR-ACT trial (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial), published literature, US Food and Drug Administration review documents, healthcare claims, and national survey data. We compared no disease-specific treatment ("usual care") with tafamidis therapy. The model reproduced 30-month survival, quality of life, and cardiovascular hospitalization rates observed in ATTR-ACT; future projections used a parametric survival model in the control arm, with constant hazards reduction in the tafamidis arm. We discounted future costs and quality-adjusted life-years by 3% annually and examined key parameter uncertainty using deterministic and probabilistic sensitivity analyses. The main outcomes were lifetime incremental cost-effectiveness ratio and annual budget impact, assessed from the US healthcare sector perspective. This study was independent of the ATTR-ACT trial sponsor. RESULTS: Compared with usual care, tafamidis was projected to add 1.29 (95% uncertainty interval, 0.47-1.75) quality-adjusted life-years at an incremental cost of $1 135 000 (872 000-1 377 000), resulting in an incremental cost-effectiveness ratio of $880 000 (697 000-1 564 000) per quality-adjusted life-year gained. Assuming a threshold of $100 000 per quality-adjusted life-year gained and current drug price, tafamidis was cost-effective in 0% of 10 000 probabilistic simulations. A 92.6% price reduction from $225 000 to $16 563 would be necessary to make tafamidis cost-effective at $100 000/quality-adjusted life-year. Results were sensitive to assumptions related to long-term effectiveness of tafamidis. Treating all eligible patients with transthyretin amyloid cardiomyopathy in the United States with tafamidis (n=120 000) was estimated to increase annual healthcare spending by $32.3 billion. CONCLUSIONS: Treatment with tafamidis is projected to produce substantial clinical benefit but would greatly exceed conventional cost-effectiveness thresholds at the current US list price. On the basis of recent US experience with high-cost cardiovascular medications, access to and uptake of this effective therapy may be limited unless there is a large reduction in drug costs.

Cost-Effectiveness of Transcatheter Mitral Valve Repair Versus Medical Therapy in Patients With Heart Failure and Secondary Mitral Regurgitation: Results From the COAPT Trial.

BACKGROUND: The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) demonstrated that edge-to-edge transcatheter mitral valve repair (TMVr) with the MitraClip resulted in reduced mortality and heart failure hospitalizations and improved quality of life compared with maximally tolerated guideline-directed medical therapy (GDMT) in patients with heart failure and 3 to 4+ secondary mitral regurgitation. Whether TMVr is cost-effective compared with GDMT in this population is unknown. METHODS: We used data from the COAPT trial to perform a formal patient-level economic analysis of TMVr+GDMT versus GDMT alone for patients with heart failure and 3 to 4+ secondary mitral regurgitation from the perspective of the US healthcare system. Costs for the index TMVr hospitalization were assessed using a combination of resource-based accounting and hospital billing data (when available). Follow-up medical care costs were estimated on the basis of medical resource use collected during the COAPT trial. Health utilities were estimated for all patients at baseline and 1, 6, 12, and 24 months with the Short Form Six-Dimension Health Survey. RESULTS: Initial costs for the TMVr procedure and index hospitalization were $35 755 and $48 198, respectively. Although follow-up costs were significantly lower with TMVr compared with GDMT ($26 654 versus $38 345; P=0.018), cumulative 2-year costs remained higher with TMVr because of the upfront cost of the index procedure ($73 416 versus $38 345; P<0.001). When in-trial survival, health utilities, and costs were modeled over a lifetime horizon, TMVr was projected to increase life expectancy by 1.13 years and quality-adjusted life-years by 0.82 years at a cost of $45 648, yielding a lifetime incremental cost-effectiveness ratio of $40 361 per life-year gained and $55 600 per quality-adjusted life-year gained. CONCLUSIONS: For symptomatic patients with heart failure and 3 to 4+ secondary mitral regurgitation, TMVr increases life expectancy and quality-adjusted life expectancy compared with GDMT at an incremental cost per quality-adjusted life-year gained that represents acceptable economic value according to current US thresholds. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01626079.

Hospital Resource Utilization Before and After Transcatheter Aortic Valve Replacement: The STS/ACC TVT Registry.

BACKGROUND: Patients with severe aortic stenosis (AS) have repeat hospitalizations for multiple conditions. OBJECTIVES: The purpose of this study was to assess the effect of transcatheter aortic valve replacement (TAVR) on hospitalizations in severe AS. METHODS: Using data from the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) registry with linkage to Medicare claims, the authors examined rates of all-cause, cardiovascular, and noncardiovascular hospitalizations and hospital days, as well as inpatient costs in the year pre-TAVR and post-TAVR. Multivariable modeling was used to determine rate ratios of post-TAVR versus pre-TAVR hospitalizations and costs. RESULTS: Among 15,324 patients at 328 sites with Medicare linkage undergoing TAVR, the median age was 84 years, the median Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.0, and 61.1% patients underwent TAVR via transfemoral access. Post-TAVR, heart failure hospitalization rates and hospitalized days were reduced compared with pre-TAVR (rate ratio: 0.87 and 0.95 respectively; p < 0.01 for all). However, all-cause, noncardiovascular, and bleeding hospitalization rates and hospitalized days were increased (p < 0.01 for all). Post-TAVR hospitalizations were reduced the most among those with left ventricular ejection fraction <30%. Mean post-TAVR costs were reduced among all TAVR patients and among 1-year survivors (rate ratio: 0.95, p < 0.01; and 0.90; p < 0.01, respectively). CONCLUSIONS: Patients had lower costs and fewer heart failure hospitalizations but more all-cause, noncardiovascular, and bleeding hospitalizations post-TAVR. Reduction in hospitalizations varied by specific patient subgroups, and thus, payors and providers seeking to reduce resource use may consider strategies designed to improve processes of care among patients with increased resource utilization post-TAVR as compared with pre-TAVR.

In-Hospital Costs and Costs of Complications of Chronic Total Occlusion Angioplasty: Insights From the OPEN-CTO Registry.

OBJECTIVES: The aim of this study was to describe the costs of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and the association of complications during CTO PCI with costs and length of stay (LOS). BACKGROUND: CTO PCI generally requires more procedural resources and carries higher risk for complications than PCI of non-CTO vessels. The costs of CTO PCI using the hybrid approach have not been described, and no studies have examined the impact of complications on in-hospital costs and LOS in this population. METHODS: Costs were calculated for 964 patients in the 12-center OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry using prospectively collected resource utilization and billing data. Multivariate models were developed to estimate the incremental costs and LOS associated with complications. Attributable costs and LOS were calculated by multiplying the independent cost of each event by its frequency in the population. RESULTS: Mean costs for the index hospitalization were $17,048 ± 9,904; 14.5% of patients experienced at least 1 complication. Patients with complications had higher mean hospital costs (by $8,603) and LOS (by 1.5 days) than patients without complications. Seven complications were independently associated with increased costs and 6 with LOS; clinically significant perforation and myocardial infarction had the greatest attributable cost per patient. Overall, complications accounted for $911 per patient in hospital costs (5.3% of the total costs) and 0.2 days of additional LOS. CONCLUSIONS: Complications have a significant impact on both LOS and in-hospital costs for patients undergoing CTO PCI. Methods to identify high-risk patients and develop strategies to prevent complications may reduce CTO PCI costs.