A cost-effectiveness analysis of patiromer for the treatment of hyperkalemia in chronic kidney disease patients with and without heart failure in Spain

Figures & data

Table 1. Baseline patient demographic and clinical characteristics.

Characteristics	Mean (SE)
Age, years	65.3 (0.89)
Female, %	46.0% (5.0%)
CDK stage, %^a
Stage 3	58.9% (4.8%)
Stage 4	41.1% (4.8%)
HF, %	45.8% (4.8%)
HF stage, %
NHYA I	18.4% (5.5%)
NYHA II	65.3% (6.8%)
NYHA III	16.3% (5.3%)
Serum potassium, %
>5.5 to ≤6 mmol/L	81.4% (3.2%)
>6 mmol/L	18.6% (3.2%)
Concomitant medication, %
Diuretics	51.4% (4.8%)
Beta blocker	60.7% (4.7%)
Statin	8.0% (0.8%)
Allopurinol	10.0% (0.9%)
RAASi medication, %
ACE	70.1% (4.4%)
ARB	37.4% (4.7%)

Source: Weir et al.^8,10.

^aPatients were described only as “stage 4 or worse”. Thus, the proportion of patients in stage 5 is unknown and was assumed as 0.

Abbreviations. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blockers; CKD, chronic kidney disease; HF, heart failure; NYHA, New York Heart Association; RAASi, renin-angiotensin-aldosterone system inhibitors; SE, Standard error.

Figure 1. Markov model for HK in CKD patients with or without HF. The squares represent different health states that are mutually exclusive. CKD stages 3–4 and NHYA I–IV represent starting health states. Abbreviations. CKD, chronic kidney disease; HF, heart failure; HK, hyperkalemia; MACE, major adverse cardiac events; NYHA, New York Heart Association; RAASi, renin-angiotensin-aldosterone system inhibitors.

Table 2. Costs and utilities included.

Parameter	Mean (SE)	Distribution	Source
Drug acquisition costs (daily)
Patiromer 8.4 g	€7.34 (−)		^30
Patiromer 16.8 g	€9.89 (−)		^30
ACE inhibitors	€0.09 (−)		^30
ARB	€0.40 (−)		^30
MRA	€0.58 (−)		^30
Health state costs
CKD management
CKD stage 3 (annual)	€4,842 (€484^a)	Gamma	^27
CKD stage 4 (annual)	€8,180 (€818^a)	Gamma	^25
CKD stage 5 (pre-renal replacement therapy) (annual)	€13,866 (€1,387^a)	Gamma	^25
Dialysis (annual)	€49,189 (€4,919^a)	Gamma	^28
Dialysis access (one-off)	€564 (€56^a)	Gamma	^24
Dialysis complications (one-off)	€5,455 (€546^a)	Gamma	^24
Transplant procedure (one-off)	€35,318 (€3,532^a)	Gamma	^24
Transplant maintenance (annual)	€7,393 (€739^a)	Gamma	^26
RAASi dose change costs (applied in month of change)
RAASi discontinuation	€194 (€19^a)	Gamma	^24^b
RAASi down-titration	€388 (€39^a)	Gamma	^24^b
Return to maximum RAASi use	€59 (€6^a)	Gamma	^24^b
Event cost
MACE	€4,369 (€437^a)	Gamma	^28
Hospitalization	€3,698 (€370^a)	Gamma	^28
Acute HK costs
K+ >5.5 to ≤6 mmol/L	€150 (€15^a)	Gamma	^24^b
K+ >6 mmol/L	€2,948 (€295^a)	Gamma	^24^b
Utilities
CKD
CKD stage 3	0.870 (0.034)	Beta	^31
CKD stage 4	0.850 (0.029)	Beta	^31
CKD stage 5 (pre-renal replacement therapy)	0.570 (0.057)	Beta	^32
Dialysis	0.452 (0.045^a)	Beta	^32
Transplant	0.710 (0.019)	Beta	^32
HF
NYHA I	0.855 (0.005)	Beta	^33
NYHA II	0.771 (0.005)	Beta	^33
NYHA III	0.673 (0.006)	Beta	^33
NYHA IV	0.532 (0.027)	Beta	^33
Events
MACE	−0.050 (0.040)	Beta	^34
Hospitalization	−0.024 (0.007)	Beta	^33
Dialysis complications	−0.060 (0.006^a)	Beta	^35^,^36

^aSE values assumed 10% of the mean. ^bExpert opinion.

Abbreviations. ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blockers; CKD, chronic kidney disease; HF, heart failure; HK, hyperkalemia; MACE, major adverse cardiac events; MRA, mineralocorticoid receptor agonist; NYHA, New York Heart Association; RAASi, renin-angiotensin-aldosterone system inhibitors; SE, Standard error.

Table 3. Base case and one-way scenario analyses results: patiromer vs. no patiromer (€2021).

Base-case analysis	Patiromer	No patiromer	Incremental
Total costs (/patient)	€119,642	€116,068	€3,574
Acquisition of drugs	€1,527	€0	€1,527
Acute HK management	€994	€1,174	−€180
CKD management	€45,585	€44,039	€1,546
Renal replacement therapy management	€42,917	€42,646	€271
MACE	€6,138	€6,211	−€73
Hospitalization	€21,147	€20,674	€473
RAASi drug usage	€594	€486	€108
RAASi change dose	€740	€838	−€98
Health outcomes
QALYs	5.76	5.57	0.19
LYG	7.73	7.50	0.23
ICERs
Cost per QALY gained			€19,092
Cost per LYG			€15,236
Scenario analyses
Parameter	Base-case value	Scenario value	ICER (€/QALY)
Discount rate	3%	0%	€19,904
	3%	5%	€18,802
Time horizon	Lifetime	10 years	€16,102
	Lifetime	20 years	€17,914
Patiromer discontinuation monthly rate	10.3%	2.5%	€25,818
	10.3%	5.0%	€22,207
	10.3%	15.0%	€17,864
Proportion of patients with HF	45.8%	0%	€19,561
	45.8%	100%	€18,377
Baseline age (years)	65.3 years	68.8 years	€18,841

Abbreviations. CKD, chronic kidney disease; HK, hyperkalemia; LYG, life-year gained; MACE, major adverse cardiac events; QALY, quality-adjusted life-year; RAASi, renin-angiotensin-aldosterone system inhibitors.

Figure 2. Cost-effectiveness plane for patiromer versus no patiromer. A WTP threshold of €30,000 per QALY gained was assumed. Abbreviations. CE, cost-effectiveness; QALY, quality-adjusted life-years; WTP, willingness-to-pay.

Table

Parameter	Mean (SE)	Distribution	Source
Event incidence (month 1) – Patiromer/no patiromer, %
HK (monthly)
K+ >5 to ≤5.5 mmol/L	21.13% (3.32%)	Beta	^10
K+ >5.5 to ≤6 mmol/L	1.66% (1.04%)	Beta	^10
K+ >6 mmol/L	0.38% (0.50%)	Beta	^10
Event incidence (months 2–3) – Patiromer, %
HK (monthly probability)
K+ >5 to ≤5.5 mmol/L	14.00% (4.68%)	Beta	^10
K+ >5.5 to ≤6 mmol/L	6.10% (3.23%)	Beta	^10
K+ >6 mmol/L	1.40% (1.58%)	Beta	^10
Change in RAASi use (monthly probability)
RAASi sub-max/max to discontinuation	3.34% (2.42%)	Beta	^10
RAASi max to down-titration	0% (0%)	Beta	^10
Event incidence (months 2–3) – No patiromer, %
HK (monthly probability)
K+ >5 to ≤5.5 mmol/L	15.00% (4.81%)	Beta	^10
K+ >5.5 to ≤6 mmol/L	25.22% (5.86%)	Beta	^10
K+ >6 mmol/L	5.78% (3.15%)	Beta	^10
Change in RAASi use (monthly probability)
RAASi sub-max/max to discontinuation	34.44% (6.59%)	Beta	^10
RAASi max to down-titration	35.55% (6.59%)	Beta	^10
Event incidence (months 4+) – patiromer/no patiromer, %
HK (annual event rate)
K+ >5 to ≤5.5 mmol/L	0.140 (0.014^a)	Gamma	^12
K+ >5.5 to ≤6 mmol/L	0.011 (0.001^a)	Gamma	^12
K+ >6 mmol/L	0.003 (0.0003^a)	Gamma	^12
Change in RAASi use (monthly probability)
RAASi sub-max/max to discontinuation
K+ ≤5 mmol/L	2.60% (0.03%)	Beta	^13
K+ >5 to ≤5.5 mmol/L	3.03% (0.10%)	Beta	^13
K+ >5.5 to ≤6 mmol/L	4.55% (0.23%)	Beta	^13
K+ >6 mmol/L	10.00% (0.66%)	Beta	^13
RAASi max to down-titration
K+ ≤5 mmol/L	1.80% (0.03%)	Beta	^13
K+ >5 to ≤5.5 mmol/L	2.62% (0.10%)	Beta	^13
K+ >5.5 to ≤6 mmol/L	5.31% (0.23%)	Beta	^13
K+ >6 mmol/L	8.90% (0.64%)	Beta	^13
RAASi max following discontinuation	3.51% (0.35%)	Beta	^13
CKD patients
CKD progression (monthly probability)
CKD stage 3 to CKD stage 4	1.66% (0.17%^a)	Beta	^14
CKD stage 4 to CKD stage 5	0.58% (0.06%^a)	Beta	^14
CKD stage 5 to dialysis	12.64% (1.61%)	Beta	^15
CKD stage 5 to transplant	1.68% (0.17%^a)	Beta	^16
Dialysis to transplant	0.52% (0.05%^a)	Beta	^16
Dialysis to death	0.96% (0.10%^a)	Beta	^17
Transplant to dialysis (graft failure)	0.19% (0.02%^a)	Beta	^16
Transplant to death	0.18% (0.02%^a)	Beta	^16
MACE (annual event rate)
CKD stage 3	0.048 (0.001)	Gamma	^18
CKD stage 4	0.218 (0.013)	Gamma	^18
CKD stage 5	0.366 (0.045)	Gamma	^18
Hospitalization (annual event rate)
CKD stage 3	0.214 (0.002)	Gamma	^18
CKD stage 4	0.868 (0.020)	Gamma	^18
CKD stage 5	1.446 (0.078)	Gamma	^18
All-cause mortality (annual event rate)
CKD stage 3	0.016 (0.001)	Gamma	^18
CKD stage 4	0.114 (0.009)	Gamma	^18
CKD stage 5	0.141 (0.031)	Gamma	^18
HF patients
HF progression (monthly)
NYHA I to NYHA I	79.56% (2.07%)	Beta	^19
NYHA I to NYHA II	12.45% (1.69%)	Beta	^19
NYHA I to NYHA III	7.38% (1.34%)	Beta	^19
NYHA I to NYHA IV	0.61% (0.40%)	Beta	^19
NYHA II to NYHA I	7.10% (1.32%)	Beta	^19
NYHA II to NYHA II	84.48% (1.86%)	Beta	^19
NYHA II to NYHA III	7.65% (1.36%)	Beta	^19
NYHA II to NYHA IV	0.77% (0.45%)	Beta	^19
NYHA III to NYHA I	0.47% (0.35%)	Beta	^19
NYHA III to NYHA II	8.93% (1.46%)	Beta	^19
NYHA III to NYHA III	88.45% (1.64%)	Beta	^19
NYHA III to NYHA IV	2.16% (0.75%)	Beta	^19
NYHA IV to NYHA I	0% (0%)	Beta	^19
NYHA IV to NYHA II	10.64% (1.58%)	Beta	^19
NYHA IV to NYHA III	10.64% (1.58%)	Beta	^19
NYHA IV to NYHA IV	78.72% (2.10%)	Beta	^19
MACE (annual event rate)
Off RAASi	0.290 (0.004)	Gamma	Assumption
Maximum RAASi	0.148 (0.003)	Gamma	^13
Sub-maximum RAASi	0.290 (0.004)	Gamma	^13
Hospitalization (monthly probability)
NYHA I	1.52% (0.15%^a)	Beta	^20
NYHA II	2.40% (0.24%^a)	Beta	^20
NYHA III	2.40% (0.24%^a)	Beta	^20
NYHA IV	15.40% (1.54%^a)	Beta	^20
RAASi odds ratio
HK event
Max/sub-max vs. off	1.270 (0.020)	Normal	^12
CKD stage 3 to CKD stage 4
Max/sub-max vs. off	0.610 (0.082)	Normal	^21
CKD stage 4 to CKD stage 5
Max/sub-max vs. off	0.610 (0.082)	Normal	^21
RAASi Incidence Rate Ratio
MACE – CKD patients
Max vs. sub-max/off	0.621 (0.010)	Gamma	^13
Death – CKD patients
Max vs. sub-max/off	0.179 (0.005)	Gamma	^13
Hospitalization – HF patients
Max vs. sub-max/off	1.000 (0.000)	Gamma	Assumption

^aSE assumed as 10% of mean.

Abbreviations. CKD, chronic kidney disease; HF, heart failure; HK, hyperkalemia; MACE, major adverse cardiac events; NYHA, New York Heart Association; RAASi, renin-angiotensin-aldosterone system inhibitors; SE, Standard error.

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