Transcatheter aortic valve implantation versus surgical aortic valve replacement in severe aortic stenosis patients at low surgical mortality risk: a cost-effectiveness analysis in Belgium

Figures & data

Figure 1. The cost-effectiveness model had two stages: (A) early AEs from the PARTNER 3 trial were captured in a decision tree, which fed into (B) a Markov model that captured longer-term outcomes of patients, with four distinct health states (reproduced from gilard M, et al. Value health 2021; https://doi.org/10.1016/j.jval.2021.10.003 under the terms of the creative commons licence (creative commons attribution license (CC by)). Clinical events were taken from the PARTNER 3 trial and from Belgian-specific literature sources when available and relevant. Costs were based on costing information from the Belgian APR-DRGs, regional tariffs and literature sources when relevant, and actualised to 2022 (Table 1 and Supplementary Materials). As there is no formal WTP threshold in Belgium, we adopted a cost-effectiveness ratio threshold of €30 000 per QALY gained. AE: adverse event; AF: atrial fibrillation; APR-DRG: All Patients Refined-Diagnosis Related Group; QALY: quality adjusted life years; SAVR: surgical aortic valve replacement; TAVI: transcatheter aortic valve implantation; WTP: willingness-to-pay.

Table 1. Costs associated with TAVI and SAVR (procedure, complications, long-term).

Unit cost components	TAVI with SAPIEN 3	SAVR	Source
Procedure
Intervention	€ 28 501.69	€ 19 766.47	APR-DRG 163 [22] + Ishak et al. [23] + Edwards estimates for valve cost, indexed to 2022
Rehabilitation	€ 1 508.74	€ 4 379.67	Gilard et al. [6], indexed to 2022
Associated to 30-days AE and intercurrent events (indexed to 2022)
Non-disabling stroke	€ 7 328.62		APR-DRG 45 (2020, minor & average only) [22]
Transient ischaemic attack (TIA)	€ 4 272.98		APR-DRG 47 (2020) [22]
Myocardial infarction	€ 4 546.30		APR-DRG 190 (2020) [22]
Bleeding	€ 9 978.31		APR-DRG 661 (2020) [22]
Acute kidney injury with renal replacement therapy	€ 64 093.96		De Smedt et al. [24], Elseviers et al. [25]
Pacemaker complications (monthly)	€ 135.59		Neyt et al. [26], indexed to 2022
Associated to health states
Treated AF - Month 1	€ 4 076.54		Pirson et al. [27] + KCE Report 184B [28] indexed to 2022
Treated AF ≥ Month 2	€ 30.49
Disabling stroke - Month 1	€ 14 891.75		APR-DRG 45 (2020, major & extreme only) [22], Dewilde et al. [29], indexed to 2022
Disabling stroke ≥ Month 2	€ 4 246.09
Alive and well - Month 1–12 (monthly)	€ 68.60		KCE Report 163 [30], indexed to 2022
Alive and well > Month 12 (monthly)	€ 2.89		Assumption
Other costs considered
Pacemaker procedure	€ 3 578.69		RIZIV/INAMI 2022 [31]
Rehospitalization	€ 8 347.87		APR-DRG 94 (2020) [22], indexed to 2022
Reintervention	€ 30 822.26		Assumed equal to cost of TAVI initial procedure plus rehabilitation associated with procedure

APR-DRG: All Patients Refined-Diagnosis Related Group; SAVR: surgical aortic valve replacement; TAVI: transcatheter aortic valve implantation.

Table 2. Base case results with acute and lifetime costs.

Summary results	TAVI with SAPIEN 3	SAVR	Incremental
Cost per patient	€ 42 741	€ 45 753	– € 3 013
Life year gained (undiscounted)	13.01	12.17	0.84
Median survival (years)	15.42	13.42	2.00
QALYs per patient	8.83	7.89	0.94
Incremental cost-effectiveness ratio (ICER)			Dominant
Incremental net monetary benefit (NMB)			€ 31 314
Incremental net health benefit (NHB)			1.04
Acute phase cost (first hospitalisation and rehabilitation)
Index hospitalisation	€ 28 733	€ 19 908	€ 8 824
Rehabilitation	€ 1 509	€ 4 380	–€ 2 871
Acute phase costs	€ 30 241	€ 24 288	€ 5 953
Additional costs at 1 year
30-days AE	€ 643	€ 3 299	–€ 2 656
Intercurrent events	€ 441	€ 184	€ 258
Costs of pacemaker complications	€ 93	€ 57	€ 36
Costs of rehospitalizations	€ 571	€ 852	–€ 282
Re-intervention costs	€ 142	€ 141	€ 1
Alive & well health state costs	€ 765	€ 513	€ 252
Treated AF health state costs	€ 226	€ 1 609	–€ 1 383
Disabling stroke costs	€ 21	€ 322	–€ 301
Total costs at 1 year	€ 33 144	€ 31 264	€ 1 880
Additional lifetime costs
Costs of pacemaker complications	€ 986	€ 570	€ 417
Costs of rehospitalizations	€ 941	€ 885	€ 56
Re-intervention costs	€ 4 517	€ 3 915	€ 602
Alive & well health state costs	€ 297	€ 187	€ 110
Treated AF health state costs	€ 557	€ 1 492	–€ 935
Disabling stroke costs	€ 2 299	€ 7 441	–€ 5 143
Additional Lifetime Costs	€ 9 596	€ 14 489	–€ 4 893
Total Lifetime Costs	€ 42 741	€ 45 753	–€ 3 013

AF: atrial fibrillation; ICER: incremental cost-effectiveness ratio; MI: myocardial infarction; NHB: incremental net health benefit; NMB: incremental net monetary benefit; QALY: quality adjusted life years; SAVR: surgical aortic valve replacement; TAVI: transcatheter aortic valve implantation.

Table 3. Change over time in (A) model outputs and (B) cost-saving assessments.

(A)
Years	Per patient cost delta - TAVI vs SAVR (Euro)	Per patient QALY delta - TAVI vs SAVR	ICER (Euro/QALY)
1	€ 1 880	0.044	€ 42 289
2	€ 1 508	0.092	€ 16 417
3	€ 1 101	0.139	€ 7 916
4	€ 670	0.187	€ 3 582
5	€ 225	0.236	€ 955
6	-€ 222	0.285	dominant
10	–€ 1 847	0.483	dominant
15	–€ 3 005	0.712	dominant
50	–€ 3 013	0.943	dominant
(B)
Years	Maximal valve price to remain cost-saving over time (Euro)
1	€ 17 730
2	€ 18 102
3	€ 18 509
4	€ 18 940
5	€ 19 385
10	€ 21 457
15	€ 22 615
50	€ 22 623

ICER: incremental cost-effectiveness ratio; QALY: quality adjusted life year; SAVR: surgical aortic valve replacement; TAVI: transcatheter aortic valve implantation.

Table 4. Scenario analyses.

Scenario No.	Description	Incremental Costs (Euro) TAVI vs SAVR	Incremental QALYs TAVI vs SAVR	ICER (Euro/QALY)
	Base case	–€ 3 013	0.94	Dominant
1	More aggressive reintervention rate for TAVR (P2A trial data at 5 years [34])	+€ 6 919	0.93	7 472
2	Survival data from PARTNER 3, HR = 0.75	–€ 4 182	1.63	Dominant
3	Survival data from PARTNER 3 estimating there is no survival benefit, HR = 1	–€ 7 016	0.57	Dominant
4	2019 annual mortality risk obtained from Belgian federal government data	–€ 3 145	0.96	Dominant
5	2018 annual mortality risk obtained from Belgian federal government data w/o cardiovascular death	–€ 4 247	1.06	Dominant
6	2019 annual mortality risk obtained from Belgian federal government data w/o cardiovascular death	–€ 4 323	1.08	Dominant
7	PPI rates as per Beyersdorf et al. [35] – GARY registry. 4.6% of patients after SAVR and 18.1% after TAVI	–€ 763	0.94	Dominant
8	Monthly transition probability from AF to Disabling stroke taken from Odutayo et al. [20] (0.010%)	+€ 188	0.91	206
9	Utility from PARTNER 3 EQ-5D-5L (disutility by treatment)	–€ 3 013	0.54	Dominant
10	Alternate AF disutility − 0.114 from Jacobs et al. [36]	–€ 3 013	0.92	Dominant
11	Alternate Disabling stroke disutility − 0.423 - subtracted from the utility value of the population norm for the same age group in Belgium [29]	–€ 3 013	0.95	Dominant
12	Procedure cost calculated as per Rapoport et al. [37]	–€ 4 011	0.94	Dominant
13	Procedure cost as per a weighting of Ishak et al. [23] and Rapoport et al. [37]	–€ 2 897	0.94	Dominant
14	Procedure cost as per expert estimate	–€ 4 469	0.94	Dominant
15	Price of device at parity with Reimbursement price from INAMI (€ 12 876)	–€ 9 848	0.94	Dominant
16	Price of device at parity with NEW Reimbursement price from INAMI - effective May 2023 (€ 11 818)	–€ 10 921	0.94	Dominant
17	Rehabilitation rates identical for TAVI and SAVR (20.9%)	+€ 146	0.94	155
18	PPI cost calculated as per Neyt et al. [26] (€ 12 401.98)	–€ 2 785	0.71	Dominant
19	Non-inclusion of AEs cost occurring before 30 days	–€ 369	0.94	Dominant
20	Time horizon = 5 years	+€ 225	0.24	955
21	Time horizon = 6 years	-€ 222	0.28	Dominant
22	Time horizon = 10 years	–€ 1 847	0.48	Dominant
23	Time horizon = 15 years	–€ 3 005	0.71	Dominant
24	Time horizon = 20 years	–€ 3 150	0.87	Dominant
25	Time horizon = 30 years	–€ 3 014	0.94	Dominant

AE: adverse event; AF: atrial fibrillation; EQ-5D-5L: Euro-Qol-5: Dimensions-5 Levels; HR: hazard ratio; P2A: PARTNER 2 trial; PPI: permanent pacemaker implantation; QALY: quality adjusted life years; SAVR: surgical aortic valve replacement; TAVI: transcatheter aortic valve implantation; w/o: without.

Figure 2. Deterministic sensitivity analysis. Tornado diagram showing the 10 parameters with greatest influence on the model. AF: atrial fibrillation; ICER: incremental cost-effectiveness ratio; QALY: quality adjusted life years; SAVR: surgical aortic valve replacement; TAVI: transcatheter aortic valve implantation.

Figure 3. (A) Probabilistic sensitivity analysis. (B) Cost-effectiveness acceptability curve. QALY: quality adjusted life years; WTP: Willingness-to-Pay.

APR-DRG. TCT (Technical cell for the processing of the data related to the hospitals), "National database medical diagnosis/care & cost - Financial feedback by pathology: APR-DRG. 2020. https://tct.fgov.be/webetct/etct-web/national_data?lang=nl&menuSelected=apr_drg&selectedSideMenu=default&reset=true

 Google Scholar

Ishak KJ, Stolar M, Hu MY, et al. Accounting for the relationship between per diem cost and LOS when estimating hospitalization costs. BMC Health Serv Res. 2012;12(1):439. doi:10.1186/1472-6963-12-439.

 PubMedGoogle Scholar

Gilard M, Eltchaninoff H, Iung B, et al. Cost-Effectiveness analysis of SAPIEN 3 transcatheter aortic valve implantation procedure compared with surgery in patients with severe aortic stenosis at low risk of surgical mortality in France. Value Health. 2022;25(4):605–613. doi:10.1016/j.jval.2021.10.003.

 PubMed Web of Science ®Google Scholar

De Smedt DM, Elseviers MM, Lins RL, et al. Economic evaluation of different treatment modalities in acute kidney injury. Nephrol Dial Transplant. 2012;27(11):4095–4101. doi:10.1093/ndt/gfs410.

 PubMed Web of Science ®Google Scholar

Elseviers MM, Lins RL, Van der Niepen P, et al. Renal replacement therapy is an independent risk factor for mortality in critically ill patients with acute kidney injury. Crit Care. 2010;14(6):R221. doi:10.1186/cc9355.

 PubMed Web of Science ®Google Scholar

Neyt M, Stroobandt S, Obyn C, et al. Cost-effectiveness of cardiac resynchronisation therapy for patients with moderate-to-severe heart failure: a lifetime markov model. BMJ Open. 2011;1(2):e000276–e000276. doi:10.1136/bmjopen-2011-000276.

 PubMed Web of Science ®Google Scholar

Pirson M, Di Pierdomenico L, Gusman J, et al. Evaluation of the cost of atrial fibrillation during emergency hospitalization. Acta Cardiol. 2013;68(5):469–474. doi:10.1080/ac.68.5.2994469.

 PubMed Web of Science ®Google Scholar

Van Brabandt H, Neyt M, Devos C. Catheter ablation of atrial fibrillation. Health Technology Assessment (HTA). Brussels. Belgian Health Care Knowledge Centre (KCE). KCE Reports 184. 2012. https://kce.fgov.be/en/publications/all-reports/catheter-ablation-of-atrial-fibrillation

 Google Scholar

Dewilde S, Annemans L, Lloyd A, et al. The combined impact of dependency on caregivers, disability, and coping strategy on quality of life after ischemic stroke. Health Qual Life Outcomes. 2019;17(1):31. doi:10.1186/s12955-018-1069-6.

 PubMedGoogle Scholar

Neyt M, Van Brabandt H, Van De Sande S, et al. Transcatheter Aortic Valve Implantation (TAVI): a Health Technology Assessment Update. Health Technology Assessment (HTA). Brussels. Belgian Health Care Knowledge Centre (KCE). KCE Report 163. 2011. https://kce.fgov.be/en/publications/all-reports/transcatheter-aortic-valve-implantation-tavi-a-health-technology-assessment-update

 Google Scholar

RIZIV. Analysis of the distribution and evolution of medical practices in Belgium, in terms of volume and expenditure per insured, for 2021 - Pacemaker (1st implant). 2022.

 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

Beyersdorf F, Bauer T, Freemantle N, et al. Five-year outcome in 18 010 patients from the german aortic valve registry. Eur J Cardiothorac Surg. 2021;60(5):1139–1146. doi:10.1093/ejcts/ezab216.

 PubMed Web of Science ®Google Scholar

Odutayo A, Wong CX, Hsiao AJ, et al. Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis. BMJ. 2016;354:i4482. doi:10.1136/bmj.i4482.

 PubMed Web of Science ®Google Scholar

Jacobs MS, de Jong LA, Postma MJ, et al. Health economic evaluation of rivaroxaban in elective cardioversion of atrial fibrillation. Eur J Health Econ. 2018;19(7):957–965. doi:10.1007/s10198-017-0942-2.

 PubMed Web of Science ®Google Scholar

Rapoport J, Teres D, Zhao Y, et al. Length of stay data as a guide to hospital economic performance for ICU patients. Med Care. 2003;41(3):386–397. doi:10.1097/01.MLR.0000053021.93198.96.

 PubMed Web of Science ®Google Scholar