Cost-Effectiveness Analysis of the Adjunctive Therapy of Ivabradine for the Treatment of Heart Failure with Reduced Ejection Fraction

Figures & data

Figure 1 Analytical decision model.

Abbreviations: CV, cardiovascular; HF, heart failure; HFrEF, heart failure with reduced ejection fraction.

Table 1 Clinical Input Parameters

Parameters	Value	Range	References
Risk of CV mortality
Standard^a	0.0211	0.0183–0.0211	Swedberg, et al^Citation3
Ivabradine^b	0.0193	0.0166–0.0220	Swedberg, et al^Citation3
Annual CV mortality rate from hospitalization	0.15		Thailand database^Citation13
Risk of CV mortality from hospitalization
Standard^c	0.0032	0.0022–0.0042	Calculation
Ivabradine^d	0.0029	0.0020–0.0038	Calculation
Risk of CV mortality from non-hospitalization
Standard^e	0.0179	0.0154–0.0204	Calculation
Ivabradine^f	0.0164	0.0140–0.0188	Calculation
Risk of CV mortality (subgroup population with baseline HR ≥77 bpm)
Standard^g	0.0248	0.0205–0.0291	Calculation
Ivabradine^h	0.0202	0.0163–0.0241	Calculation
Risk of non-CV mortality by age ≥60 years
60	0.0035		Burden of disease in Thai population,^Citation15 Health statistics^Citation16
65	0.0053
70	0.0080
75	0.0128
80	0.0203
≥85	0.0357
Risk of HF hospitalization
Standard	0.0297	0.0263–0.0331	Swedberg, et al^Citation3
Ivabradine	0.0224	0.0195–0.0253	Swedberg, et al^Citation3
Risk of all-cause 30-day readmission
Risk of all-cause 30-day readmission for standard^i	0.2882	0.2594–0.3171	Thailand database^Citation13
Relative risk of all-cause 30-day readmission ivabradine vs standard^j	0.833	0.669–1.014	Komajda, et al^Citation17
Risk of all-cause 30-day readmission for ivabradine^k	0.2401		Calculation

Notes: ^a3-month rate = -[ln(1–15.04%)]/(22.9/3) = 0.0214. Then 3-month probability = 1 − exp(- 0.0214) = 0.0211. ^b3-month rate = −[ln(1–13.85%)]/(22.9/3) = 0.0195. Then 3-month probability = 1 − exp(−0.0195) = 0.0193. ^c1-year CV mortality rate = 0.0214 × (12/3) = 8.54%. Of those 8.54%, 15% died from hospitalization; therefore, 1-year CV hospitalization mortality rate = 15% × 8.54% = 1.28%. Risk of CV mortality from hospitalization for 3 months = 1 − exp(- 1.8% × (3/12)) = 0.0032. ^d1-year CV mortality rate = 0.0195 × (12/3) = 7.81%. Of those 7.81%, 15% died from hospitalization; therefore, 1-year CV hospitalization mortality rate = 15% × 7.81% = 1.17%. Risk of CV mortality from hospitalization for 3-month period = 1 − exp(−1.17% × (3/12)) = 0.0029. ^eRisk of CV mortality from non-hospitalization for 3-month period = 0.0211–0.0032 = 0.0179. ^fRisk of CV mortality from non-hospitalization for 3-month period = 0.0193–0.0029 = 0.0164. ^gRisk of CV mortality among ivabradine group with baseline HR ≥77bpm (3-month rate) = −[ln(1–17.47%)]/(22.9/3) = 0.0251. Then 3-month probability = 1 − exp(−0.0251) = 0.0248. ^hRisk of CV mortality among ivabradine group with baseline HR ≥77bpm = 0.0251 × 0.81 = 0.0204. Then 3-month probability = 1 − exp(−0.0204) = 0.0202. ⁱ Risk of all-cause 30-day readmission for standard treatment = 1 − exp(−34%) = 0.2882. The 34% rate of readmission was obtained from the Thai heart failure national database. ^jRelative risk = 0.78/[(1–0.2882) + (0.2882× 0.78)] = 0.833. ^kRisk of all-cause 30-day readmission for sacubitril-valsartan = 0.2882 × 0.833 = 0.2401.

Abbreviations: bpm, beats per minute; CV, cardiovascular; HF, heart failure; HR, heart rate.

Table 2 Costs and Utility Parameters

Parameters	Value	Range	References
Costs (THB)
Medications (3 months)
Standard	725.27	580.22–870.32	DMSIC^Citation18
Ivabradine	6741.00	5392.80–8089.20	Royal Gazette^Citation20
Cost of hospitalization	56,552.27	1152.69–626,058.00	Siriraj Hospital
Utility
Stable HFrEF	0.75	0.65–0.85	Adena, et al^Citation10
Hospitalization	0.65	0.55–0.75	Adena, et al^Citation10

Abbreviations: DMSIC, Drug and Medical Supply Information Center; THB, Thai baht; HFrEF; heart failure with reduced ejection fraction.

Table 3 Base-Case Results

Variables	Ivabradine	Standard
Cohort population
Total cost (THB/USD)	71,071 (2,161.54)	18,736 (569.82)
Life-years (years)	8.14	7.92
QALYs (years)	6.08	5.84
Incremental cost-effectiveness ratio
THB/life-year (USD/life-year)	240,132 (7,303.30)
THB/QALY (USD/QALY)	214,219 (6,515.16)
Subgroup analysis for patients with HR ≥77bpm
Total cost (THB/USD)	69,627 (2,117.61)	17,207 (523.33)
Life-years (years)	8.05	7.25
QALYs	5.96	5.35
Incremental cost-effectiveness ratio
THB/life-year (USD/life-year)	65,690 (1,997.88)
THB/QALY (USD/QALY)	86,317 (2,625.20)

Abbreviations: bpm, beats per minute; QALYs, quality-adjusted life-years; THB, Thai baht; USD United States dollars.

Figure 2 Tornado diagram of ivabradine plus standard treatment compared with standard treatment alone. (A) Cohort population. (B) Subgroup population with baseline HR ≥77 bpm.

Abbreviations: CV, cardiovascular; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HR, heart rate; QALY, quality-adjusted life-year; THB, Thai baht.

Figure 3 Analysis of the incremental cost-effectiveness ratio relative to changes in the daily cost of ivabradine.

Abbreviations: QALY, quality-adjusted life-year; THB, Thai baht.

Figure 4 Scatter plots of 1000 iterations for ivabradine plus standard treatment compared with standard treatment alone on a cost-effectiveness plane. (A) Cohort population. (B) Subgroup population with baseline HR ≥77 bpm.

Abbreviations: bpm, beats per minute; HR, heart rate; QALY, quality-adjusted life-year; THB, Thai baht.

Figure 5 Cost-effectiveness acceptability curve of ivabradine plus standard treatment compared with standard treatment alone. (A) Cohort population. (B) Subgroup population with baseline HR ≥77 bpm.

Abbreviations: bpm, beats per minute; HR, heart rate; QALY, quality-adjusted life-year; THB, Thai baht.

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