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

Figures & data

Figure 1. Markov model based on complications observed in patients with ssAS. Abbreviations. PVL, Paravalvular leakage; SAVR, Surgical aortic valve replacement; ssAS, Severe Symptomatic Aortic Stenosis; TAVI, Transcatheter Aortic Valve Implantation.

Table 1. Clinical event probabilities and utilities used in the model.

	Intermediate Risk			Low Risk
Clinical events	TAVI with SAPIEN 3	SAVR	Source	TAVI with SAPIEN 3	SAVR	Source
Probabilities of peri-operative complications at 30 days
Death	1.1%	4.0%	PARTNER II S3i^12	0.4%	1.1%	PARTNER 3 trial^10
Stroke	2.7%	6.1%		0.6%	2.4%
New pacemaker implantation	10.2%	7.3%		6.5%	4.0%
Kidney failure	0.5%	3.3%		0.4%	1.8%
Major bleeding	4.6%	46.7%		3.6%	24.5%
Myocardial infarction	0.3%	1.9%		1.0%	1.3%
Major vascular complications	6.1%	5.4%		2.2%	1.5%
Atrial fibrillation	5.0%	28.3%		5.0%	39.5%
Rehospitalization	4.6%	6.8%		3.4%	6.5%
Probabilities of post-operative complications at 1 year for intermediate-risk patients and 2 years for low-risk patients
Death	7.4%	13.0%	PARTNER II S3i^9^,^12	2.4%	3.2%	PARTNER 3 trial^10^,^11
Disabling stroke	2.3%	5.9%		0.8%	1.1%
Dialysis	2.2%	5.2%		0.2%	0.7%
Moderate/severe PVL	1.5%	0.4%		0.5%	0%
Rehospitalization	11.4%	15.1%		8.5%	12.5%
Utilities
Prior to intervention	0.733	0.727	^18^,^19	0.769	0.770	^19^,^20
Discharge to 6 months post-AVR	0.799	0.738		0.847	0.758
Post-AVR, 6 months–1 year	0.799	0.738		0.840	0.841
Post-AVR, >1 year	0.791	0.785		0.825	0.832
Disabling stroke	−0.265	−0.265	^21	−0.265	−0.265	^21
Dialysis	0.616	0.616	^22	0.744	0.744	^22

Abbreviations. PVL: Paravalvular Leakage; SAVR: Surgical Aortic Valve Replacement; TAVI: Transcatheter Aortic Valve Implantation.

Table 2. Breakdown of TAVI and SAVR cost.

	TAVI with SAPIEN 3	Source	SAVR	Source
Peri-operative costs
Device cost	¥4,510,000 (code: 710010745)	^29	¥984,000	Claims data analysis^a
Procedure fee	¥390,600 (code: K555-2)	^30	¥855,000 (code: K555)	^30
Incremental cost of procedural complications
Other hospitalization cost^b	¥1,234,828	Regression analysis^c	¥3,554,266	Regression analysis^c
In-hospital mortality	¥1,516,442		¥2,474,105
Stroke	¥1,121,531		¥1,894,908
Pacemaker implantation	¥1,566,299		¥1,841,697
Kidney failure	¥1,823,416		¥1,058,893
Myocardial infarction	¥801,742		¥55,515
Vascular complications	¥584,013		¥1,514,380
Atrial fibrillation	¥367,480		¥181,276
Major bleeding	¥652,892	^31	¥652,892	^31
Rehospitalization	¥1,175,859	Claims data analysis^d	¥1,197,655	Claims data analysis^d
Post-operative costs (assumed to be the same for patients who underwent TAVI with SAPIEN 3 and SAVR)^e
	Cost		Source
Disabling stroke	¥405,200		^32
Dialysis	¥400,000		^33
Rehospitalization	¥854,947		Claims data analysis^f

^aBased on the median of SAVR device cost in the MDV analysis (2019–2022Q2).

^bBased on the MDV regression analysis (2019–2022Q2).

^cExcluding device, procedure and complications.

^dBased on the rehospitalization cost within 30 days from discharge in MDV analysis (2019-2022Q2).

^eThis assumption is consistent with previous work.³⁴

^fBased on the hospitalization cost with heart failure in MDV analysis (2019–2022Q2).

Abbreviations. MDV: Medical Data Vision; SAVR: Surgical Aortic Valve Replacement; TAVI: Transcatheter Aortic Valve Implantation.

Table 3. Base case analysis.

	Lifetime Total Costs (¥)	Lifetime Total QALYs	Lifetime LYs	ICER (¥/QALY) (=ΔCosts/ ΔQALYs)
Intermediate-risk patients
SAVR	10,155,688	4.37	6.41
TAVI	7,973,013	5.33	7.48
Incremental value	−2,182,674	0.96	1.07	Dominant
Low-risk patients
SAVR	6,491,360	6.45	8.62
TAVI	6,710,900	6.74	9.01
Incremental value	219,540	0.29	0.39	750,417

Abbreviations. ICER: Incremental Cost-Effectiveness Ratio; LY: Life Year; QALY: Quality-Adjusted Life Year; SAVR: Surgical Aortic Valve Replacement; TAVI: Transcatheter Aortic Valve Replacement.

Figure 2. Tornado diagrams of deterministic sensitivity analysis. A. Patients with intermediate surgical risk. B. Patients with low surgical risk. Abbreviations. QALY, Quality-Adjusted Life Year; SAVR, Surgical Aortic Valve Replacement; TAVI, Transcatheter Aortic Valve Implantation.

Figure 3. Probabilistic sensitivity analysis. A. Patients with intermediate surgical risk. B. Patients with low surgical risk. Abbreviations. QALY, Quality-Adjusted Life-Years; WTP, Willingness-To-Pay.

Table 4. Scenario analysis: Testing different patient starting age.

	Starting age: 83 years (Base Case)			Starting age: 77.5 years^a
	Total Costs (¥)	Total QALYs	ICER (¥/QALY) (=ΔCosts/ΔQALYs)	Total Costs (¥)	Total QALYs	ICER (¥/QALY) (=ΔCosts/ΔQALYs)
Intermediate-risk patients
SAVR	10,155,688	4.37		11,545,830	5.96
TAVI	7,973,013	5.33		8,428,640	7.29
Incremental value	−2,182,674	0.96	Dominant	−3,149,321	1.33	Dominant
Low-risk patients
SAVR	6,491,360	6.45		6,630,181	8.09
TAVI	6,710,900	6.74		6,794,613	8.46
Incremental value	219,540	0.29	750,417	164,431	0.38	437,412

^aModeling from 77.5 years to represent the mid-point between 75–80 years, the “grey area” in the Japanese Circulation Society Clinical Guidelines.³⁸

Abbreviations. ICER, Incremental Cost-Effectiveness Ratio; QALY, Quality-Adjusted Life-Year; SAVR, Surgical Aortic Valve Replacement; TAVI, Transcatheter Aortic Valve Implantation.

Table 5. Scenario analysis: Testing different long-term mortality benefits.

	Long-Term Mortality HR = 1 (Base Case)			Long-Term Mortality HR = 1.09^a (Scenario 1)			Long Term Mortality HR = 0.9^b (Scenario 2)
	Total Costs (¥)	Total QALYs	ICER (¥/QALY) (=ΔCosts/ΔQALYs)	Total Costs (¥)	Total QALYs	ICER (¥/QALY)^c (=ΔCosts/ΔQALYs)	Total Costs (¥)	Total QALYs	ICER (¥/QALY) (=ΔCosts/ΔQALYs)
Intermediate-risk patients
SAVR	10,155,688	4.37		10,155,688	4.37		10,155,688	4.37
TAVI	7,973,013	5.33		7,913,529	5.11		8,048,327	5.60
Incremental value	−2,182,674	0.96	Dominant	−2,242,159	0.75	Dominant	−2,107,360	1.20	Dominant
Low-risk patients
SAVR	6,491,360	6.45		6,491,360	6.45		6,491,360	6.45
TAVI	6,710,900	6.74		6,701,967	6.56		6,722,268	6.98
Incremental value	219,540	0.29	750,417	210,608	0.11	1,989,801	230,908	0.53	435,484

^aAssumes long-term mortality hazard for TAVI vs SAVR (through lifetime) is 1.09, based on the 5-year hazard ratio reported in the PARTNER 2 5-year publication.⁴²

^bAssumes long-term mortality hazard is 0.9, based on the 5-year hazard ratio reported in the PARTNER 2 S3i 5-year publication.³⁹

Abbreviations. HR, Hazard ratio; ICER, Incremental cost-effectiveness ratio; QALY, Quality-adjusted life year; SAVR, Surgical aortic valve replacement; TAVI, Transcatheter aortic valve implantation.

Thourani VH, Kodali S, Makkar RR, et al. Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Lancet. 2016;387(10034):2218–2225. doi: 10.1016/S0140-6736(16)30073-3.

 PubMed Web of Science ®Google Scholar

Mack MJ, Leon MB, Thourani VH, et al. 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.

 PubMed Web of Science ®Google Scholar

Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374(17):1609–1620. doi: 10.1056/NEJMoa1514616.

 PubMed Web of Science ®Google Scholar

Leon MB, Mack MJ, Hahn RT, et al. Outcomes 2 years after transcatheter aortic valve replacement in patients at low surgical risk. J Am Coll Cardiol. 2021;77(9):1149–1161. doi: 10.1016/j.jacc.2020.12.052.

 PubMed Web of Science ®Google Scholar

Baron SJ, Thourani VH, Kodali S, et al. Effect of SAPIEN 3 transcatheter valve implantation on health status in patients with severe aortic stenosis at intermediate surgical risk: results from the PARTNER S3i trial. JACC: cardiovascular Interventions. 2018;11(12):1188–1198.

 PubMed Web of Science ®Google Scholar

Shiroiwa T, Fukuda T, Ikeda S, et al. Japanese population norms for preference-based measures: EQ-5D-3L, EQ-5D-5L, and SF-6D. Qual Life Res. 2016;25(3):707–719. doi: 10.1007/s11136-015-1108-2.

 PubMed Web of Science ®Google Scholar

Baron SJ, Magnuson EA, Lu M, et al. Health status after transcatheter versus surgical aortic valve replacement in low-risk patients with aortic stenosis. J Am Coll Cardiol. 2019;74(23):2833–2842. doi: 10.1016/j.jacc.2019.09.007.

 PubMed Web of Science ®Google Scholar

Shiroiwa T, Noto S, Fukuda T. Japanese population norms of EQ-5D-5L and health utilities index mark 3: disutility catalog by disease and symptom in community settings. Value Health. 2021;24(8):1193–1202. doi: 10.1016/j.jval.2021.03.010.

 PubMed Web of Science ®Google Scholar

Shimizu U, Aoki H, Sakagami M, et al. Walking ability, anxiety and depression, significantly decrease EuroQol 5-Dimension 5-level scores in older hemodialysis patients in Japan. Arch Gerontol Geriatr. 2018;78:96–100. doi: 10.1016/j.archger.2018.06.006.

 PubMed Web of Science ®Google Scholar

Medical fee information provision service: transcatheter prosthesis valve set: Ministry of Health, Labour and Welfare. 2022 [21 Mar 2023]. Available from: https://shinryohoshu.mhlw.go.jp/shinryohoshu/searchMenu/doSearchInputTp.

 Google Scholar

Medical fee information provision service: transcatheter valve replacement: Ministry of Health, Labour and Welfare. 2022 [21 March 2023]. Available from: https://shinryohoshu.mhlw.go.jp/shinryohoshu/searchMenu/doSearchInputSp.

 Google Scholar

Kamae I, Hashimoto Y, Koretsune Y, et al. Cost-effectiveness analysis of apixaban against warfarin for stroke prevention in patients with nonvalvular atrial fibrillation in Japan. Clin Ther. 2015;37(12):2837–2851. doi: 10.1016/j.clinthera.2015.10.007.

 PubMed Web of Science ®Google Scholar

Hattori N, Hirayama T, Katayama Y. Medical care for chronic-phase stroke in Japan. Neurol Med Chir. 2012;52(4):175–180. doi: 10.2176/nmc.52.175.

 PubMed Web of Science ®Google Scholar

Cost of dialysis treatment: Cost burden when receiving dialysis. Available at. https://www.zjk.or.jp/kidney-disease/expense/dialysis/. [21 Mar 2023]. Available from: https://www.zjk.or.jp/kidney-disease/expense/dialysis/.

 Google Scholar

Inoue S, Nakao K, Hanyu M, et al. Cost-effectiveness of transcatheter aortic valve implantation using a balloon-expandable valve in Japan: experience from the Japanese pilot health technology assessment. Value Health Reg Issues. 2020;21:82–90. doi: 10.1016/j.vhri.2019.07.013.

 PubMedGoogle Scholar

Izumi C, Eishi K, Ashihara K, et al. JCS/JSCS/JATS/JSVS 2020 guidelines on the management of valvular heart disease. Circ J. 2020;84(11):2037–2119. doi: 10.1253/circj.CJ-20-0135.

 PubMed Web of Science ®Google Scholar

Makkar RR, Thourani VH, Mack MJ, et al. Five-year outcomes of transcatheter or surgical aortic-valve replacement. N Engl J Med. 2020;382(9):799–809. doi: 10.1056/NEJMoa1910555.

 PubMed Web of Science ®Google Scholar

Madhavan MV, Kodali SK, Thourani VH, et al. Outcomes of SAPIEN 3 transcatheter aortic valve replacement compared with surgical valve replacement in intermediate-risk patients. J Am Coll Cardiol. 2023;82(2):109–123. doi: 10.1016/j.jacc.2023.04.049.

 PubMed Web of Science ®Google Scholar