Cost-utility of dapagliflozin plus standard treatment compared to standard treatment for the management of heart failure with reduced ejection fraction in Colombia

Figures & data

Table 1. Baseline characteristics of the DAPA-HF study population and relevant subgroups [11,14,15]

Characteristic (SE)	All	With DM2	Without DM2	Age ≤ 65	Age > 65
Age (years)	66.34 (0.16)	66.52 (0.21)	66.20 (0.23)	56.30 (0.17)	73.86 (0.11)
Women	0.23 (0.01)	0.22 (0.01)	0.24 (0.01)	0.21 (0.01)	0.25 (0.01)
BMI (kg/m2)	28.15 (0.09)	29.30 (0.13)	27.21 (0.11)	28.93 (0.15)	27.57 (0.10)
KCCQ TSS Q1: 0-<58	0.23 (0.01)	0.27 (0.01)	0.20 (0.01)	0.26 (0.01)	0.21 (0.01)
KCCQ TSS Q2: 58-<77	0.25 (0.01)	0.25 (0.01)	0.25 (0.01)	0.24 (0.01)	0.25 (0.01)
KCCQ TSS Q3: 77-<92	0.28 (0.01)	0.25 (0.01)	0.30 (0.01)	0.26 (0.01)	0.29 (0.01)
KCCQ TSS Q4: 92–100	0.24 (0.01)	0.23 (0.01)	0.25 (0.01)	0.23 (0.01)	0.25 (0.01)
NT-proBNP (pg/mL)	2342.53 (43.52)	2464.83 (66.72)	2242.03 (57.20)	2062.04 (53.82)	2552.48 (64.26)
Ischemic HF	0.56 (0.01)	0.62 (0.01)	0.51 (0.01)	0.49 (0.01)	0.62 (0.01)
Duration of HHF > 2 years	0.62 (0.01)	0.64 (0.02)	0.62 (0.02)	0.56 (0.02)	0.67 (0.02)
Previous HF	0.47 (0.01)	0.49 (0.01)	0.46 (0.01)	0.49 (0.01)	0.47 (0.01)
LVEF	0.31 (0.00)	0.31 (0.00)	0.31 (0.00)	0.30 (0.00)	0.32 (0.00)
Creatinine (μmol/L)	104.44 (0.44)	108.99 (0.70)	100.71 (0.55)	99.42 (0.68)	108.20 (0.57)
DM2	0.45 (0.01)	1.00 (0.00)	0.00 (0.00)	0.46 (0.01)	0.45 (0.01)

Note: BMI: Body mass index, DM2: Type 2 diabetes mellitus, HF: Heart failure, HHF: Hospitalization for heart failure, KCCQ-TSS: Kansas City Cardiomyopathy Questionnaire-Total Symptom Score, LVEF: Left ventricular ejection fraction, NT-proBNP: N-terminal pro B-type natriuretic peptide, SE: Standard error.

Table 2. Model parameters

Health state	Average	SE	Source
Standard treatment (%)
ACE inhibitor	34.2	–	Recolfaca Registry [17]
ARB	42.1	–	Recolfaca Registry [17]
ARNi (sacubitril/valsartan)	11.0	–	Recolfaca Registry [17]
MRA	56.2	–	Recolfaca Registry [17]
Betablocker	88.0	–	Recolfaca Registry [17]
Diuretic	68.3	–	Recolfaca Registry [17]
Acquisition costs
Dapagliflozin + SoC	$514.0	–	SISMED [29]
SoC	$ 142.4	–	SISMED [29]
Cost of health states
Heart failure care	$ 121.1	$ 12.0	Experts
DM2 ^a	$ 264.6	$ 26.5	González et al [40]
HHF ^b	$ 2,422.3	$ 242.2	Tamayo et al [41]
UHF	$ 163.9	$ 16.4	Experts
CV death ^c	$ 3,944.6	$ 394.5	Mendoza et al. [31]
Cost of adverse events
Volume depletion ^d	$ 17.2	$ 1.7	McMurray et al [25]
Renal events ^e	$ 29.4	$ 2.9	McMurray et al [25]
Hypoglycemic events ^f	$ 226.4	$ 22.6	Enciso [42]
Fractures ^g	$ 873.9	$ 87.4	García et al [43]
Diabetic ketoacidosis ^h	$ 548.4	$ 54.8	Experts
Amputation ^h	$ 6,870.8	$ 687.1	Experts
Incidence of adverse events (Dapa+Soc/SoC)
Volume depletion	0.0500/0.0450	0.009/ 0.008	DAPA-HF [11]
Renal events	0.0410/ 0.0470	0.008/ 0.009	DAPA-HF [11]
Hypoglycemic events	0.0010/ 0.001	0.0010/ 0.001	DAPA-HF [11]
Fractures	0.0140/ 0.0140	0.005/ 0.005	DAPA-HF [11]
Diabetic ketoacidosis	0.0010/ 0.0450	0.0500/0.0450	DAPA-HF [11]
Amputation	0.0030/ 0.0030	0.002/ 0.002	DAPA-HF [11]
Utilities
KCCQ TSS: 1 – <58	0.600	0.016	DAPA-HF [11]
KCCQ TSS: 58 – <77	0.705	0.016	DAPA-HF [11]
KCCQ TSS: 77 – <92	0.773	0.016	DAPA-HF [11]
KCCQ TSS: 92– 100	0.833	0.016	DAPA-HF [11]
DM2 (decrease)	0.017	0.003	DAPA-HF [11]
HHF (decrease)	0.321	0.020	DAPA-HF [11]
UHF (decrease)	0.036	0.011	DAPA-HF [11]
Volume depletion	0.051	0.012	DAPA-HF [11]
Renal events	0.076	0.014	DAPA-HF [11]
Hypoglycemic events	0.014	0.001	Currie et al, [44], Beaudet et al, [45]
Fractures	0.149	0.033	DAPA-HF [11]
Diabetic ketoacidosis	0.000	0.000	Assumption
Amputation	0.280	0.053	UKPDS 62 [46], Beaudet et al, [45]
Others
Discontinuation of dapagliflozin (%)	7.00	7.00	DAPA-HF [11]

Note: ACE inhibitor: Angiotensin-converting-enzyme inhibitors, ARB: Angiotensin II receptor blockers, ARNi: angiotensin receptor neprilysin inhibitor, CPI: Consumer Price Index, DM1: Type 1 diabetes mellitus, DM2: Type 2 diabetes mellitus, MER: Market exchange rate, HHF: Heart failure hospitalization, KCCQ TSS: Kansas City Cardiomyopathy Questionnaire-Total Symptom Score. MRA: mineralocorticoid receptor antagonists, SE: Standard error, SoC: Standard of care, UHF: Urgent Heart failure visit

Table footnote: ^aThe average cost per patient per year was taken into account from the perspective of the third party payer. MER 2007: $2,076; CPI: 104.97/64.23, ^b The average cost of the event was taken into account and adjusted with the CPI: 104.97/75.42, ^c The cost of an acute myocardial infarction was used and adjusted with the CPI: 104.97/85.37, ^d A hypotension event was considered and an adjustment was made with the CPI: 104.97/85.37, ^e A elevated creatinine event was considered and an adjustment was made with the CPI: 104.97/85.37, ^f A severe hypoglycemia event was considered and an adjustment was made with the CPI: 104.97/85.37, ^g The costs of emergencies, hospitalization and rehabilitation of a non-vertebral fracture are included and an adjustment was made with the CPI: 104.97/75.42, ^h Cost-generating events were based on the DM1 guideline [47] and the amounts were validated with clinical experts.

Figure 1. Model structure in heart failure analysis

CV: cardiovascular; HF: Heart failure; KCCQ: Kansas City Cardiomyopathy Questionnaire; T2DM: Type 2 diabetes mellitus

Figure 2. Tornado diagram

Figure 3. Simulations on the cost-effectiveness plane

Table 3. Results of the base case

	Dapagliflozin + SoC	Placebo + SoC	Incremental
Acquisition and follow-up
Treatment costs	$ 1,687.9	$ 495.6	$ 1,192.3
Medical management (follow-up)	$ 860.0	$ 824.0	$ 36.0
Clinical events
HHF	$ 889.1	$ 1,140.9	-$ 251.7
UHF	$ 2.1	$ 4.7	-$ 2.6
CV death	$ 1,172.1	$ 1,343.2	-$ 171.1
Total cost	$ 4,611.2	$ 3,808.3	$ 802.9
QALYs by health status
KCCQ TSS: 0-<58	0.342	0.370	−0.028
KCCQ TSS: 58-<77	0.570	0.590	−0.020
KCCQ TSS: 77-<92	0.785	0.761	0.025
KCCQ TSS: 92–100	1.002	0.846	0.156
Clinical events
HHF	−0.010	−0.013	0.003
UHF	0.000	0.000	0.000
Disutility for adverse events	0.000	0.000	0.000
Total QALY	2.689	2.554	0.135
ICER ($/QALY gained)			USD $5,946

Note: SoC: Standard of care, HHF: Heart failure hospitalization, UHF: Heart failure emergencies, KCCQ-TSS: Kansas City Cardiomyopathy Questionnaire-Total Symptom Score, QALY: Quality-adjusted life years, ICER: Incremental cost-effectiveness ratio.

Table 4. Cost effectiveness results in specific subgroups

	Subgroup
	All	With DM2	Without DM2	≤ 65 years	> 65 years
Costs
Dapagliflozin + SoC	$4,611.2	$5,475.9	$3,926.0	$4,589.2	$4,535.3
Placebo + SoC	$3,808.3	$4,766.6	$3,054.5	$3,752.4	$3,770.2
Incremental	$802.9	$709.3	$871.5	$836.8	$765.1
Life years
Dapagliflozin + SoC	3.624	3.475	3.734	3.720	3.468
Placebo + SoC	3.479	3.313	3.603	3.586	3.314
Incremental	0.145	0.162	0.131	0.134	0.154
Cost/LY	$5,553.1	$4,380.9	$6,656.1	$6,226.5	$4,984.2
QALY
Dapagliflozin + SoC	2.689	2.544	2.799	2.754	2.576
Placebo + SoC	2.554	2.399	2.672	2.626	2.435
Incremental	0.135	0.145	0.127	0.128	0.141
Cost/QALY	$5,945.9	$4,881.2	$6,867.5	$6,542.4	$5,440.8
NMB	$1,510.2	$1,779.9	$1,302.3	$1,354.1	$1,643.7

Note: SoC: Standard of care, DM2: Type 2 diabetes mellitus, HHF: Heart failure hospitalization, UHF: Heart failure emergencies, LY: Life years, QALY: Quality-adjusted life years, ICER: Incremental cost-effectiveness ratio, NMB: Net monetary benefit.

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