Cost-effectiveness analysis of percutaneous mitral valve repair with the MitraClip delivery system for patients with mitral regurgitation in Japan

Figures & data

Figure 1. Model structure. Abbreviations. NYHA, New York Heart Association; MV, mitral valve; CHF, congestive heart failure. MitraClip complications, adverse events, re-implantation with MitraClip, MV surgery and CHF hospitalization are considered in the analytical model.

Table 1. Transition probability.

Items			MitraClip	Medical therapy	Source
Proportion of patients with each NYHA class^*1	Base-case	Class I	41.8%	3.8%	^10
		Class II	43.0%	22.2%
		Class III	13.3%	59.5%
		Class IV	1.9%	14.6%
	Scenario	Class I	33.3%	3.2%	^11
		Class II	40.7%	12.9%
		Class III	24.1%	64.5%
		Class IV	1.9%	19.4%
Mortality (/month)	Base-case		HR: 0.66*² (1.96% (/month))	3.16% (/month)	^10
	Scenario		HR: 0.492^*2	S(t)=exp(−0.1004t^0.6875)	^8
Re-implantation with MitraClip device for failed MitraClip procedure	Base-case		2.1%	-	^10
	Scenario		1.28%	-	^11
Probability of MV surgery (30 days)	Base-case		2.5%	2.5%^*3	^10
	Scenario		0.0%	14%	^11
Probability of CHF hospitalization (/month)	Base-case		4%	13%	^10
	Scenario		3%	8.7%	^11
Probability of MitraClip complication (30 days)^*4	Base-case	Major vascular complication	6.4%	-	^10
		Major bleeding complication	8.5%	-
		Non-cerebral thromboembolism	0.0%	-
	Scenario	Major vascular complication	6.4%	-	^11
		Major bleeding complication	17.9%	-
		Non-cerebral thromboembolism	0%	-
Adverse events (30 days)	Base-case	MI	1.3%	-	^10
		Stroke	2.5%	-
		Renal failure	2.1%	-
		Non-elective cardiovascular surgery	0.4%	-
		Mechanical ventilation (≥48 h)	2.5%	-
		GI complication requiring surgery	0.0%	-
		Septicemia	1.3%	-
		Blood transfusion (≥2 units of blood)	14.8%	-
Adverse events (after the 2nd month) (/month)	Base-case	MI	0.16%	-
		Stroke	0.12%	-
		Renal failure	0.32%	-
		Non-elective cardiovascular surgery	0.0%	-
		Mechanical ventilation (≥48 h)	0.36%	-
		GI complication requiring surgery	0.12%	-
		Septicemia	0.28%	-
		Blood transfusion (≥2 units of blood)	1.51%	-
Adverse events (30 days)^*5	Scenario	MI	2.6%	-	^11
		Stroke	2.6%	-
		Renal failure	3.8%	-
		Mechanical ventilation (≥48 h)	2.6%	-
		GI complication requiring surgery	1.3%	-
		Septicemia	0.0%	-
		Blood transfusion (≥2 units of blood)	28.2%	-
Adverse events (after the 2nd month)(/month)^*5	Scenario	MI	0.3%	-
		Stroke	0.0%	-
		Renal failure	0.2%	-
		Mechanical ventilation (≥48 h)	0.0%	-
		GI complication requiring surgery	0.2%	-
		Septicemia	0.3%	-
		Blood transfusion (≥2 units of blood)	1.0%	-

Abbreviations. NYHA, New York Heart Association; HR, hazard ratio; MV, mitral valve; CHF, congestive heart failure; MI, myocardial infarction; GI, gastrointestinal; OS, overall survival.

^*1For MitraClip group, 12-month postoperative values in the clinical trials (6-month postoperative values only in AVJ-514) were used. The values at baseline of MitraClip group were used for medical therapy group.

^*2HR of OS for MitraClip against medical therapy.

^*3It was assumed to be the same as the value for MitraClip group in Velazquez¹⁰.

^*4Events including MitraClip complications; Major vascular complication: hematomas exceeding 6 cm of puncture, retroperitoneal hematoma, arteriovenous fistula, symptomatic peripheral ischemia/clinical signs or nerve injury with symptoms persist for more than 24 h, surgical repair of puncture vessel, Ipsilateral deep venous thrombosis, Major bleeding complication: bleeding requiring surgery, bleeding requiring blood transfusion (more than 2 units), Non-cerebral thromboembolism: paroxysmal atrial fibrillation, persistent atrial fibrillation, arrhythmia requiring cardiac block/pacemaker. MitraClip complications were not considered in the scenario analysis 3 since there is no report in AVJ-514 on complications targeted in the analysis.

^*5Non-elective cardiovascular surgery was not considered in the scenario analysis 2 since it was not evaluated in the previous study by Cameron et al.⁸

Table 2. Cost.

Items				MitraClip	Medical therapy	Source
Device cost for MitraClip (JPY)				3,057,535	-	^16
Technical fee for MitraClip procedure (JPY)				349,300	-	^17
Cost other than device cost and technical fee for MitraClip (Interatrial septum paracentesis) (JPY)				124,400	-	^17
Cost for MitraClip procedure hospitalization (JPY/event)				262,654	-	^14^,^17
Cost for MV surgery (JPY/event)				7,365,553	-	Claims data calculation
Cost for CHF hospitalization (JPY/event)				997,544	-	Claims data calculation
Treatment cost for MitraClip complication (JPY/event)			Major vascular complication	216,321	-	^17
			Major bleeding complication	5,500	-	^17
			Non-cerebral thromboembolism^*1		-
Drug cost (JPY/month)	0–1 month			14,865	15,678	^13^,^18
	≥2 months			14,807	15,678
Follow-up cost (JPY/month)^*2	0–1 month			15,760	4,668	Expert opinions,^17
	2–12 months			5,860	4,668
	≥1 year			4,668	4,688
Adverse events (JPY/event)	0–1 month	MI^*3		1,927,462	-	Claims data calculation
		Stroke^*3		1,382,356	-	Claims data calculation
		Renal failure^*3		1,465,396	-	Claims data calculation
		Non-elective cardiovascular surgery		5,500	-	^17
		Mechanical ventilation (≥48 h)^*4		45,864	-	Claims data calculation,^17
		GI complication requiring surgery^*5		46,000	-	^14^,^17
		Septicemia^*6		438,350	-	^14
		Blood transfusion (≥2 units)^*7		36,638	-	Claims data calculation,^17
	2 month	MI		1,927,462	-	Claims data calculation
		Stroke		1,382,356	-	Claims data calculation
		Renal failure		1,465,396	-	Claims data calculation
		Non-elective cardiovascular surgery		5,500	-	^17
		Mechanical ventilation (≥48 h)^*4		184,652	-	Claims data calculation,^17
		GI complication requiring surgery		273,910	-	^14^,^17
		Septicemia		438,350	-	^14
		Blood transfusion (≥2 units)^*7		36,638	-	Claims data calculation,^17

Abbreviations. MV, mitral valve; CHF, congestive heart failure; MI, myocardial infarction; GI, gastrointestinal; DPC, Diagnosis Procedure Combination; LOS, length of stay.

^*1It is not considered in the analysis since there is no incidence of “non-cerebral thromboembolism” in the group pooled with EVEREST II HRS and REALISM.

^*2Follow-up cost for MitraClip group after the 2nd year onwards is used for follow-up cost for medical therapy group.

^*3As the hospitalization costs for “MI”, “stroke” and “renal failure” are higher than the cost for “MitraClip procedure hospitalization”, the cost for “MitraClip procedure hospitalization” are included in the hospitalization cost for each event.

^*4As the hospitalization cost for “mechanical ventilation >48h” in 30 days is included in the cost for “MitraClip procedure hospitalization”, only the medical fee for mechanical ventilation (45,864 JPY) is accounted. From the 2nd month onwards, the hospitalization cost for 6.8 days (138,788 JPY) calculated by claims data calculation and the medical fee for mechanical ventilation (45,864 JPY) are accounted.

^*5As the hospitalization costs for “GI complication requiring surgery” is lower than the cost for “MitraClip procedure hospitalization”, the cost for the events occurred in 30 days is included in the cost for “MitraClip procedure hospitalization”. Technical fees and material costs are counted.

^*6As the hospitalization cost for “septicemia” is set based on DPC point. “Septicemia” is assumed to occur in the same hospitalization for “MitraClip procedure”, if it occurs in 30 days, the higher hospitalization cost whichever “septicemia” or “MitraClip procedure” is counted. Therefore, the hospitalization cost for “septicemia” is not calculated in the scenario analysis 1 because “MitraClip procedure hospitalization” exceeds the hospitalization cost of “septicemia”.

^*7As for hospitalization for blood transfusion, because the units of transfusion are calculated for the patients with MV surgery, LOS for the event cannot be calculated for those patients. Thus, only the cost for blood transfusion is included.

Table 3. QOL value.

Items		MitraClip	Medical therapy	Source
NYHA class	Class I	0.900	0.900	^19
	Class II	0.830	0.830
	Class III	0.740	0.740
	Class IV	0.598	0.598
Disutility for MitraClip procedure		−0.043	-	^20
Disutility for MV surgery		−0.074	−0.074	^21
Disutility for CHF hospitalization		−0.064	−0.064	^22

Abbreviations. QOL, quality of life; NYHA, New York Heart Association; MV, mitral valve; CHF, congestive heart failure.

Figure 2. Tornado diagram. For parameters with asterisk (*), 95% CI is used as a range of sensitively analysis. The range of ±20% of baseline value is chosen for the rest of parameters. Abbreviations. ICER, incremental cost-effectiveness ratio; QALY, quality adjusted life year; HR, hazard ratio; OS, overall survival; CHF, congestive heart failure; NYHA, New York Heart Association; MI, myocardial infarction; MV, mitral valve; CI, confidence interval.

Figure 3. Probabilistic sensitivity analysis. (A) Cost-effectiveness plane, and (B) cost-effectiveness acceptability curve. Abbreviations. QALY, quality adjusted life year; WTP, willingness to pay.

Table 4. Results of base-case and scenario analysis.

	QALY	LY (years)	Cost (JPY)	ICER (JPY/QALY)	ICER (JPY/LY)
(1) Base-case analysis
MitraClip	3.2312	3.8519	7,541,151	1,968,389	1,996,778
Medical therapy	1.7876	2.4289	4,699,692
(2) Scenario analysis^*1
MitraClip	4.6709	5.6642	8,153,892	1,304,314	1,198,355
Medical therapy	1.9266	2.6772	4,574,425

Abbreviations. QALY, quality adjusted life year; LY, life year; ICER, incremental cost-effectiveness ratio.

^*1Analysis using parameters on Canadian CEA (Cameron et al.⁸).

Velazquez EJ, Samad Z, Al-Khalidi HR, et al. The MitraClip and survival in patients with mitral regurgitation at high risk for surgery: a propensity-matched comparison. Am Heart J. 2015;170(5):1050.e3–1059.e3.

 Web of Science ®Google Scholar

Whitlow PL, Feldman T, Pedersen WR, et al. Acute and 12-month results with catheter-based mitral valve leaflet repair: the EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study. J Am Coll Cardiol. 2012;59(2):130–139.

 PubMed Web of Science ®Google Scholar

Cameron HL, Bernard LM, Garmo VS, et al. A Canadian cost-effectiveness analysis of transcatheter mitral valve repair with the MitraClip system in high surgical risk patients with significant mitral regurgitation. J Med Econ. 2014;17(8):599–615.

 PubMedGoogle Scholar

Insurance Reimbursement for Medical Devices (to be listed in April 2018) [Internet]. Tokyo (Japan): Central Social Insurance Medical Council; 2018 [cited 2019 Aug 16]. Available from: https://www.mhlw.go.jp/file/05-Shingikai-12404000-Hokenkyoku-Iryouka/0000192797.pdf

 Google Scholar

Shinryou tensuu hayami hyou 2017-nen 4-gatsu ban [Medical treatment fee point April 2017]. Tokyo: Igakutsushinsha Co,; 2017. Japanese.

 Google Scholar

DPC tensuu hayami hyou 2017-nen 4-gatsu ban [DPC point table (April 2017 edition)]. Tokyo: Igakutsushinsha Co.; 2017. Japanese.

 Google Scholar

Abbott Vascular Co., Ltd. MitraClip STED 8.1.7 Clinical Results of AVJ-514 trial. Tokyo: Abbott Vascular Co., Ltd. (Japan); 2016.

 Google Scholar

Nihon iyakuhin shuu DB 2017-nen 4-gatsu ban [Japanese Drugs DB April 2017]. Tokyo: Jiho, Inc.; 2017. Japanese.

 Google Scholar

Gohler A, Geisler BP, Manne JM, et al. Utility estimates for decision-analytic modeling in chronic heart failure–health states based on New York Heart Association classes and number of rehospitalizations. Value in Health: J Int Soc Pharmacoecon Outc Res. 2009;12:185–187.

 Google Scholar

Chaplin S, Scuffham PA, Alon M, et al. Secondary prevention after PCI: the cost-effectiveness of statin therapy in the Netherlands. Netherlands Heart J. 2004;12:331–336.

 PubMedGoogle Scholar

Marwick TH, Scuffham PA, Hunink MG. Selection for early surgery in asymptomatic mitral regurgitation: a Markov model. Int J Cardiol. 2013;165(2):266–272.

 PubMed Web of Science ®Google Scholar

Sullivan PW, Ghushchyan V. Preference-based EQ-5D index scores for chronic conditions in the United States. Med Decis Making. 2006;26(4):410–420.

 PubMed Web of Science ®Google Scholar