A Canadian cost-effectiveness analysis of transcatheter mitral valve repair with the MitraClip system in high surgical risk patients with significant mitral regurgitation

Figures & data

Figure 1. Simplified Schematic of the Model.

Figure 2. Observed and modelled overall survival.

Table 1. Base case model inputs for transition probabilities and probability of events.

Analysis parameter	Base case input		Reference(s)
	MitraClip therapy	CC
Probability of MitraClip complication^a			Whitlow et al.18
Major vascular complication	0.064	N/A
Major bleeding complication	0.179	N/A
Non-cerebral thromboembolism	0.0	N/A
30-day probability of MitraClip adverse event^b			Whitlow et al.18
Myocardial infarction	0.026	N/A
Major stroke	0.026	N/A
Renal failure	0.038	N/A
Mechanical ventilation >48 h	0.026	N/A
GI complication requiring surgery	0.013	N/A
Septicemia	0.0	N/A
Blood transfusion (≥2 units of blood)	0.282	N/A
Re-implantation with MitraClip device for failed MitraClip procedure (%)	1.28	N/A	Whitlow et al.18
NYHA Class (%)			Whitlow et al.18
Class I	33.3	3.2
Class II	40.7	12.9
Class III	24.1	64.5
Class IV	1.9	19.4
Probability of MV surgery (lifetime)	0.0	0.14	Whitlow et al.18
Probability of CHF hospitalization (monthly)	0.03	0.087	Whitlow et al.18
Adverse event rate (per month)^c
Myocardial infarction	0.003	0.0	MitraClip group: Whitlow et al.18 CC: Assumptions
Major stroke	0.0	0.0
Renal failure	0.002	0.0
Mechanical ventilation >48 h	0.0	0.0
GI complication requiring surgery	0.002	0.0
Septicemia	0.003	0.0
Blood transfusion (≥2 units of blood)	0.01	0.0
Health utilities and utility decrements^d
Health utility for NYHA class			Göhler et al.47
Class I	0.90	0.90
Class II	0.83	0.83
Class III	0.74	0.74
Class IV	0.598	0.598
Decrement for CHF hospitalization^e	−0.064	−0.064	Sullivan and Ghushchyan53
Decrement for MitraClip procedure^f	−0.043		Chaplin et al.54
Decrement for MV surgery^g	−0.074	−0.074	Marwick et al.55

^aThe probability for each of these complications was applied in the first month of the model according to the event rates reported in the 30-day periprocedural period of the EVEREST II HRS.

^bThe probability of major adverse events for the 30-day periprocedural period was applied in the first month of the model for patients receiving the MitraClip device.

^cThe 12-month probability of major adverse events following the MitraClip procedure was converted to a monthly probability and was applied for the duration of the analysis. In the absence of data regarding the risk of adverse events in medically managed patients, a probability of 0 was assumed for all events.

^dHealth utilities and utility decrements were assumed to be the same for the MitraClip and concurrent comparator groups.

^eThe decrement for CHF-related hospitalization was applied during each model cycle in which hospitalization occurred.

^fThe decrement for the MitraClip procedure was assumed to be the same as that for other percutaneous coronary interventions (PCIs) and was applied for 1 month.

^gThe decrement for MV surgery was applied as 10% of the disutility for NYHA Class III for the first year (12 cycles), similar to the methodology reported by Marwick et al.55.

CHF, Congestive Heart Failure; GI, Gastrointestinal; CC, Concurrent Comparator; NYHA, New York Heart Institute.

Table 2. Resource utilization and costs associated with the MitraClip procedure.

Resource	Quantity	Unit cost ($CDN)	Total Cost ($CDN)	Reference(s)
Device costs
MitraClip device^a	1 device	30,000	30,000	Abbott Vascular
Pre-procedural costs
Cardiology consultation^b	1 visit	157.00	157.00	Quantity: Clinical experience Unit cost: OHIP SOBs64
Cardiac surgery consultation^c	1 visit	90.30	90.30	Quantity: Clinical experience Unit cost: OHIP SOBs64
Transesophageal echocardiography^d	1 test	285.40	285.40	Quantity: Clinical experience Unit cost: OHIP SOBs64
Transthoracic echocardiography^e	1 test	148.65	148.65	Quantity: Clinical experience Unit cost: OHIP SOBs64
Chest x-ray^f	1 test	23.58	23.58	Quantity: Clinical experience Unit cost: OHIP SOBs64
Electrocardiogram^g	1 test	11.05	11.05	Quantity: Clinical experience Unit cost: OHIP SOBs64
Laboratory evaluations^h	228 units	0.517	117.88	Quantity: Clinical experience Unit cost: OHIP SOBs63
Peri-procedural costs
Intensive care unit^i	2.2 days	1444.00/day	3176.80	Quantity: EVEREST II HRS Unit Cost: Sunnybrook HSC62
Cardiac ward^i	1.7 days	492.00/day	836.40	Quantity: EVEREST II HRS Unit Cost: Sunnybrook HSC62
Anesthesiologist^j	1 fees	637.00	637.00	Quantity: Clinical experience Unit cost: OHIP SOBs64
Respiratory therapist^k	1 fees	108.96	108.96	Quantity: Clinical experience Unit Cost: Sunnybrook HSC62
Cardiologist^l	2 fees	1618.50	3237.00	Quantity: Clinical experience Unit Cost: OHIP SOBs64
Transesophageal echocardiography^d	1 test	285.40	285.40	Quantity: Clinical experience Unit cost: OHIP SOBs64
Transthoracic echocardiography^e	1 test	148.65	148.65	Quantity: Clinical experience Unit cost: OHIP SOBs64
Disposables^m	1 set	175.00	175.00	Quantity: Expert opinion Unit cost: Expert opinion
Vascular closure device	3 devices	325.00	975.00	Quantity: Clinical experience Unit Cost: Sunnybrook HSC62
Medications^n	1 dose	2.86	52.86	Quantity: Clinical experience Unit cost: BC Pharmacare74
Total cost of MitraClip device and procedure:			$42,025.88

^aCost of the MitraClip device is a flat cost of $30,000, irrespective of how many clips are utilized.

^bPhysician code A605 from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64.

^cPhysician code A095 from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64.

^dDiagnostic codes G570, G571, G572, G579, G580, and G581 from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64. Includes cost of test and cost of interpretation.

^eDiagnostic codes G570 and G571 from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64. Includes cost of test and cost of interpretation.

^fDiagnostic codes X091 (two views) from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64. Includes cost of test and cost of interpretation.

^gDiagnostic codes G310 and G313 from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64. Includes cost of test and cost of interpretation.

^hLaboratory evaluations are a fixed amount based on the standard laboratory tests requested prior to the MitraClip procedure and include the following: complete blood count (CBC); electrolytes, urea, creatinine; amino-terminal pro-B-type natriuretic peptide (NT-proBNP); prothrombin time (PT), partial thromboplastin time (PTT), International Normalized Ratio (INR). Assumes a total of four tests at 57 units per test (@0.517 per unit) from the Ontario Health Insurance Plan Schedule of Benefits for Laboratory Services63.

ⁱLength of hospital stay was based on the Whitlow et al.18 mean length of stay in the intensive care unit (52.3 h) and the mean total time spent in hospital post-procedure (3.9 days).

^jIncludes 28 units anesthesia with R773 at 15.01 per unit and 18 units assistant with R773 at 12.04 per unit.

^kCost of 54.48 per hour provided by the Sunnybrook Health Science Center.

^lPhysician cardiovascular surgery procedure code R773 for simple mitral valve repair (including annuloplasty) from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64.

^mDisposables include transseptal needle, catheters, Mullins sheath, etc.

ⁿAssumes 10,000 units/mL heparin.

BC, British Columbia; CDN, Canadian; HSC, Health Sciences Center; NYHA, New York Heart Institute; OHIP, Ontario Health Insurance Plan; SOBs, Schedule of Benefits.

Table 3. Resource utilization and costs associated with clinical events and disease management.

Resource	Quantity	Unit cost ($CDN)	Reference(s)
Hospitalization for CHF	1	7186	Unit cost: OCCI CMG 19657
MV surgery	1	26,348	Unit cost: OCCI Procedure Codes 1HU80LA, 1HU80LAFE,1HU80LAXXA57
MitraClip complications
Major vascular complication	1	5233	Unit cost59
Major bleeding complication	1	7118	Unit cost58
Non-cerebral thromboembolism	1	7142	Unit cost: OCCI CMG 21057
Adverse events
Myocardial infarction	1	7700	Unit cost: OCCI CMG 19457
Major stroke	1	6890	Unit cost: OCCI CMG 02857
Renal failure	1	6493	Unit cost: OCCI CMG 47757
Mechanical ventilation >48 h^a	1	2888	Unit cost62
GI complication requiring surgery	1	5832	Unit cost61
Septicemia	1	13,047	Unit cost: OCCI CMG 65457
Blood transfusion (≥2 units of blood)	1	535.51	Unit cost: Tretiak et al.60
Disease management* (per month)
Heart failure clinic visit^b	0.25	157.88	Quantity: Clinical experience Unit Cost: OHIP SOBs64
Repeat cardiology consultation^c	0.17	105.25	Quantity: Clinical experience Unit cost: OHIP SOBs64
Transthoracic echocardiogram^d	0.25	148.65	Quantity: Clinical experience Unit cost: OHIP SOBs64
Laboratory evaluations^e	0.08	29.47	Quantity: Clinical experience Unit cost: OHIP SOBs63

^aAssumes an additional 2 days stay in intensive care unit.

^bPhysician code A606 for cardiology consultation + E078 (50% for chronic disease assessment premium) from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64.

^cPhysician code A606 for repeat cardiology from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64.

^dDiagnostic codes G570 and G571 from the Ontario Health Insurance Plan Schedule of Benefits for Physician Services64. Includes cost of test and cost of interpretation.

^eLaboratory evaluations are a fixed amount based on the standard laboratory tests requested and include the following: complete blood count (CBC); electrolytes, urea, creatinine; amino-terminal pro-B-type natriuretic peptide (NT-proBNP); prothrombin time (PT), partial thromboplastin time (PTT), International Normalized Ratio (INR). Assumes 57 units (@0.517 per unit) from the Ontario Health Insurance Plan Schedule of Benefits for Laboratory Services63.

*Monthly disease management applies for both MitraClip and concurrent comparator group.

CDN, Canadian; CHF, Congestive Heart Failure; CMG, Case Mix Group; OCCI, Ontario Case Costing Initiative OHIP, Ontario Health Insurance Plan; SOBs, Schedule of Benefits.

Table 4. Summary of alternative parameter estimates utilized in one-way sensitivity analyses.

Variable	Base case value	Low value	High value	Reference(s)
Time horizon (years)	Lifetime	3	10	CADTH guidelines
Discounting for costs and effects (%)	5.0	0.0	3.0	CADTH guidelines
Overall survival hazard ratio for MitraClip therapy vs concurrent comparator	0.492	0.253	0.958	Whitlow et al.18; 95% CI
Probability of CHF hospitalization (monthly)
MitraClip group	0.03	0.0	0.0679	Whitlow et al.18; 95% CI
Concurrent comparator group	0.0875	0.0248	0.1502	Whitlow et al.18; 95% CI
Probability of MV surgery (lifetime)
MitraClip group	0.0	0.02	0.05	Expert opinion
Concurrent comparator group	0.14	0.027	0.253	Whitlow et al.18
Cost of MitraClip procedure ($CDN)	12,901.07	10,320.85	15,481.28	Base case ± 20%
Cost of MV surgery ($CDN)	26,348.00	23,763.15	28,932.85	Ontario Case Costing Initiative57; 95% CI
Cost of CHF hospitalization ($CDN)	7186.00	6988.67	7383.33	Ontario Case Costing Initiative57; 95% CI
Health utility for NYHA
Class I	0.9	0.93		Kirsch and McGuire48
Class II	0.83	0.77		Kirsch and McGuire48
Class III	0.74	0.51		Kirsch and McGuire48
Class IV	0.598	0.280		Kirsch and McGuire48

CADTH, Canadian Agency for Drugs and Technologies in Health; CDN, Canadian; CHF, Congestive Heart Failure; CI, Confidence Interval; NYHA, New York Heart Association.

Table 5. Summary of parameter estimates and distributions used in the probability sensitivity analysis.

Analysis parameter	Base case input (data source)	Distribution and parameters	Notes
Population starting age	77.018	Normal (µ = 77.0, SE = 1.1)	Based on SD of the mean
Males (%)	62.8%18	Normal (µ = 62.8%, SE = 0.0628)
Weibull curve for Concurrent comparator	λλ = 0.1004 γ = 0.6875	Cholesky decomposition matrix	Based on variance/ covariance matrix
Overall survival hazard ratio for MitraClip therapy vs Concurrent comparator	0.49218	Lognormal (µ = −0.7093, SE = 0.3397)	Based on 95% CI
Probability of MV surgery (lifetime)
MitraClip group	0.018	Beta (µ = 0, SE = 0.01)	Assumption
Concurrent comparator group	0.1418	Beta (µ = 0.14, SE = 0.014)	Assumed 10% variability
Probability of CHF hospitalization (monthly)
MitraClip group	3.0%18	Beta (µ = 0.03, SE = 0.003)	Assumed 10% variability
Concurrent comparator group	8.75%18	Beta (µ = 0.08745, SE = 0.008745)	Assumed 10% variability
Cost of MitraClip device ($CDN)	30,000	Gamma (µ = 30,000, SE = 3000)	Assumed 10% variability
Cost of MitraClip procedure ($CDN)	12,901.07	Gamma (µ = 12,901.07, SE = 1290.11)	Assumed 10% variability
Cost of repeat MitraClip procedure ($CDN)	12,901.07	Gamma (µ = 12,901.07, SE = 1290.11)	Assumed 10% variability
Cost of CHF hospitalization ($CDN)	7186	Gamma (µ = 7186, SE = 7082)	Based on 95% CI
Cost of MV surgery ($CDN)	26,348.00	Gamma (µ = 26,348, SE = 24,425)	Based on 95% CI
Cost of disease management costs (monthly $CDN))
MitraClip group	188.87	Gamma (µ = 188.87, SE = 18.89)	Assumed 10% variability
Concurrent comparator group	96.63	Gamma (µ = 96.63, SE = 9.66)	Assumed 10% variability
Health utilities and utility decrements
Health utility for NYHA class
		Beta
Class I	0.90	(µ = 0.90, SE = 0.037)	Variance of the mean
Class II	0.83	(µ = 0.83, SE = 0.006)
Class III	0.74	(µ = 0.74, SE = 0.009)
Class IV	0.59847	(µ = 0.598, SE = 0.026)
Decrement for CHF hospitalization	0.06453	Beta (µ = 0.06, SE = 0.0002)	Variance of the mean
Decrement for MitraClip procedure	0.04354	Beta (µ = 0.043, SE = 0.0004)	Assumed 10% variability
Decrement for MV surgery	0.07455	Beta (µ = 0.074, SE = 0.0074)	Assumed 10% variability

CHF, Congestive Heart Failure; NYHA, New York Heart Association; SD, Standard Deviation; SE, Standard Error.

Table 6. Base case analysis results for MitraClip therapy vs concurrent comparator.

Outcome	MitraClip therapy	Concurrent comparator	Incremental difference^a
Total life years per patient	3.93	2.09	1.84
Total QALYs per patient	3.24	1.51	1.73
Total costs per patient ($CDN)	62,510	21,893	40,617
MitraClip procedure	42,901	0	42,901
Repeat MitraClip procedure	538	0	538
MV surgery	0	3689	−3689
CHF hospitalizations	10,165	15,778	−5613
Disease management	8906	2426	6480
Incremental cost per QALY gained^b	–	–	23,433

^aCalculated as MitraClip therapy minus concurrent comparator.

^bCalculated as the difference in costs divided by the difference in QALYs.

CDN, Canadian; QALY, Quality-adjusted Life Year.

Table 7. Results for the one-way deterministic sensitivity analyses.

Analysis	Low value	Low value ICER ($CDN/QALY)	High value	High value ICER ($CDN/QALY)
Time horizon (years)	3	59,248	10	25,752
Discounting for costs and effects (%)	0.0	18,808	3.0	21,535
Overall survival hazard ratio for MitraClip therapy vs concurrent comparator	0.25	15,923	0.95	84,895
Probability of CHF hospitalization (monthly)
MitraClip group	0.0	17,493	0.0679	31,012
Concurrent comparator group	0.0248	30,099	0.1502	16,820
Probability of MV surgery (lifetime)
MitraClip group	0.02	23,756	0.05	24,240
Concurrent comparator group	0.027	25,244	0.253	21,636
Cost of MitraClip procedure ($CDN)	10,320.85	21,945	15,481.28	24,922
Cost of mitral valve surgery ($CDN)	23,763.15	23,225	28,932.85	23,642
Cost of CHF hospitalization ($CDN)	6988.67	23,344	7383.33	23,522
Health Utility for NYHA
Class I	0.93	23,005	N/A	N/A
Class II	0.77	24,564	N/A	N/A
Class III	0.51	22,245	N/A	N/A
Class IV	0.280	22,091	N/A	N/A

CDN, Canadian; CHF, Congestive Heart Failure; ICER, Incremental Cost-effectiveness Ratio; NYHA, New York Heart Association; QALY, Quality-adjusted Life Year.

Figure 3. Scatterplot showing the results of the incremental costs and incremental QALYs for 10,000 runs of the probabilistic sensitivity analysis. The dashed line shows acceptability thresholds of $50,000 per QALY gained. Nearly all results fall below the $50,000 threshold.

Figure 4. Cost-acceptability curve (CEAC). Cost-acceptability curve (CEAC). In approximately 92% of the runs, MitraClip therapy was cost-effective versus standard of care at a threshold of $50,000 per QALY gained.

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