Cost-effectiveness analysis of sodium zirconium cyclosilicate for hyperkalemia among patients with chronic kidney disease or heart failure in Kuwait

Figures & data

Figure 1. The health states and events in the model. Abbreviations. HF, heart failure; NYHA, New York Heart Association; MACE, Major adverse cardiovascular events; AEs, adverse events; RAASi, renin–angiotensin–aldosterone inhibitors; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; RRT, renal replacement therapy; ESRD, end stage renal disease

Table 1. The clinical parameters used in the model.

Parameters					References
Change in K level in SZC arm (captured from matched ZS-004)					[19]
Change in K level at days:	Day 0–3	Day 4 – 14	Day 15 – 28	Longer-term efficacy; Day +29
Fixed: Intercept	5.600	4.565	4.658	4.710
Random: Patient	0.225	0.213
Random: Observation	0.228	0.234
Change in K level in Patiromer arm (captured from Matched OPAL-HK)					[23]
Change in K level at days:	Day 0–3	Day 4 – 14	Day 15 – 28	Longer-term efficacy; Day +29
Fixed: Intercept	5.600	5.077	4.880	4.770
Random: Patient	0.237	0.216
Random: Observation	0.240	0.238
Change in K level in Patiromer arm (captured from Crude OPAL-HK)					[23]
Change in K level at days:	Day 0–3	Day 4 – 14	Day 15 – 28	Longer-term efficacy; Day +29
Fixed: Intercept	5.574	4.807	4.550	4.560
Random: Patient	0.322	0.429
Random: Observation	0.326	0.397
Transition probabilities among HF cohort
From\To Mean (SE)	NYHA I	NYHA II	NYHA III	NYHA IV	References
NHYA I	0.7956 (0.1)	0.1245 (0.1)	0.0738 (0.1)	0.0061 (0.1)	[26]
NYHA II	0.071 (0.1)	0.8448 (0.1)	0.0765 (0.1)	0.0077 (0.1)
NYHA III	0.0047 (0.1)	0.0893 (0.1)	0.8845 (0.1)	0.0216 (0.1)
NYHA IV	0	0.1064 (0.1)	0.1064 (0.1)	0.7872 (0.1)
K + Profile				Monthly probability of hospitalization Mean (SE)
RAASi: K + < 5.5				0.067 (0.004)	[48]
RAASi: K+ < 6.0				0.083 (0.009)
RAASi: K+ ≥ 6.0				0.117 (0.022)
No RAASi: K + < 5.5				0.105 (0.005)
No RAASi: K+ < 6.0				0.105 (0.010)
No RAASi: K+ ≥ 6.0				0.110 (0.021)
Sub RAASi: K + < 5.5				0.081 (0.005)
Sub RAASi: K+ < 6.0				0.091 (0.009)
Sub RAASi: K+ ≥ 6.0				0.114 (0.021)
All-cause mortality Mean (SE)
HR of Mortality	K + subgroup							[27]
	<3.5	3.5-3.8	3.9-4.2	4.3-4.5	4.6-5.0	5.1-5.5	>5.5
	2.19 (0.59)	1.91 (0.40)	1	1	1.47 (0.27)	2.28 (0.55)	6.6 (1.70)
Annual mean of eGFR decline (SE) in CKD cohort
CKD on RAASi				2.34 (0.023)	[28]
Annual event rate according to CKD stages (SE)
Event	CKD subgroups				[29]
	3a	3b	4	5
MACE	0.0365 (0.0012)	0.1129 (0.0012)	0.218 (0.0024)	0.366 (0.0048)
Hospitalization	0.1722 (0.0045)	0.4526 (0.0067)	0.8675 (0.0090)	1.4461 (0.0090)
All-cause mortality	0.0108 (0.0004)	0.0476 (0.0007)	0.1136 (0.0018)	0.1414 (0.0031)
IRR for events by K + subgroup mean (SE)
Event	K + subgroup							[15]
	<3.5	3.5-3.9	4-4.4	4.5-4.9	5-5.4	5.5-5.9	≥6
MACE	1.89 (0.09)	1.27 (0.04)	1.04 (0.01)	1	1.01 (0.02)	1.12 (0.04)	1.88 (0.12)
All-cause mortality	3.05 (0.29)	1.49 (0.08)	1.06 (0.04)	1	1.14 (0.06)	1.6 (0.13)	3.31 (0.46)
Hospitalization eGFR <30	1.93 (0.45)	1.65 (0.22)	0.93 (0.09)	1	1	1.34 (0.18)	3.65 (0.58)
Hospitalization eGFR 30-40	1.77 (0.34)	1.35 (0.16)	0.99 (0.08)	1	(0.10)	1.07 (0.14)	1.82 (0.44)
Hospitalization eGFR 40-50	2.24 (0.38)	1.23 (0.13)	1.08 (0.07)	1	0.96 (0.09)	1.23 (0.18)	1.91 (0.56)
Hospitalization eGFR 50-60	2.06 (0.27)	1.13 (0.08)	1.01 (0.05	1	1.07 (0.09)	0.81 (0.11)	1.07 (0.30)
Event risk by RAASi use mean (SE)
OR RAASi vs no RAASi: mortality	0.870 (0.069)	[30]
OR Sub RAASi vs no RAASi: mortality	0.935 (0.069)	Assumption
OR RAASi vs no RAASi: MACE	0.820(0.054)	[30]
OR Sub RAASi vs no RAASi: MACE	0.910(0.054)	Assumption

Abbreviations. CKD, Chronic kidney disease; eGFR, estimated glomerular filtration rate; HR, Hazard ratio; HF, Heart failure; MACE, Major adverse cardiovascular events; OR, Odds ratio; RAASi, Renin‐angiotensin‐aldosterone system inhibitors; SZC, Sodium zirconium cyclosilicate; CPRD, Clinical Practice Research Datalink; IRR, Incidence rate ratio; NYHA, New York Heart Association.

Table 2. The utility inputs in the model.

	Base case	Low value	High value	References
Utilities:
CKD 3a	0.870	0.783	0.957	32
CKD 3b	0.870	0.783	0.957
CKD 4	0.850	0.765	0.935
CKD 5	0.570	0.513	0.627	32
Dialysis	0.44	0.396	0.484
Transplant	0.710	0.639	0.781
NYHA I	0.855	0.7695	0.9405	33
NYHA II	0.771	0.6939	0.8481
NHYA III	0.673	0.6057	0.7403
NYHA IV	0.532	0.4788	0.5852
Disutility
Hospitalization	−0.024	−0.0216	−0.0264	32
Dialysis complication	−0.02	−0.018	−0.022	34
MACE	−0.05	−0.045	−0.055	35
Edema (generalized and peripheral)	−0.0029	−0.00261	−0.00319	Assumption
Worsening hypertension	−0.0029	−0.00261	−0.00319	36
Constipation	−0.0056	−0.00504	−0.00616
Diarrhea	−0.0008	−0.00072	−0.00088	37
Nausea	−0.0037	−0.00333	−0.00407	38
Hypomagnesemia	−0.00073	−0.000657	−0.000803	36
Anemia	−0.0015	−0.00135	−0.00165
UTI	−0.0004	−0.00036	−0.00044

Abbreviations. UTI, Urinary tract infection; CKD, Chronic kidney disease; MACE, Major adverse cardiovascular events; NYHA, New York Heart Association.

Table 3. Unit costs used in our model.

Cost parameters (KWD)
Intervention	Base case	Low value	High value	References
SZC 10 g	KWD 3.75	3.375	4.125	Jaber Al-Ahmed Armed Forces Hospital - Kuwait Ministry of Defense.
SZC 5 g	KWD 2.62	2.35	2.882
SPS 454 g	KWD 24.44	21.996	26.884
Patiromer (16.8 g − 8.4 g)	KWD 2.97	2.673	3.267
Furosemide 40 mg tablet	KWD 0.07	0.063	0.077
Furosemide 20 mg ampoule	KWD 0.18	0.162	0.198
Isosorbide mononitrate tab 60 mg	KWD 0.06	0.054	0.066
Amlodipine 5 mg	KWD 0.16	0.1413	0.1727
Bisacodyl 5 mg	KWD 0.01	0.0117	0.0143
Loperamide 2 mg	KWD 0.08	0.0675	0.0825
Metoclopramide 10 mg	KWD 0.02	0.0198	0.0242
Serum Mg level	KWD 1.00	0.9	1.1
Magnesium oxide 400 mg	KWD 0.03	0.0243	0.0297
Esomeprazole 20 mg	KWD 0.17	0.153	0.187
Epoetin Alpha 4,000 iu/ml	KWD 12.80	11.52	14.08
Nitrofurantoin	KWD 0.07	0.0648	0.0792
Amoxicillin/clavulanate 1 g	KWD 0.53	0.477	0.583
Physician visit	KWD 10.00	9	11
Outpatient visit	KWD 10.00	9	11
ER visit	KWD 10.00	9	11
Inpatient day (regular room)	KWD 10.00	9	11
Inpatient day (ICU room)	KWD 30.00	27	33
Serum creatinine	KWD 0.50	0.45	0.55
Urea	KWD 0.50	0.45	0.55
Serum K+	KWD 0.50	0.45	0.55
ECG	KWD 10.00	9	11
Regular insulin 100 iu/ml-3 ml	KWD 1.40	1.26	1.54
D50W (50% dextrose solution) 1,000 ml	KWD 0.78	0.702	0.858
Calcium gluconate iv. 10% w/v 10 ml	KWD 0.07	0.0657	0.0803	Jaber Al-Ahmed Armed Forces Hospital - Kuwait Ministry of Defense.
Salbutamol nebulizer2.5 mg	KWD 0.10	0.09	0.11
Ramipril 2.5 mg	KWD 0.24	0.216	0.264
Ramipril 5 mg	KWD 0.25	0.225	0.275
Ramipril 10 mg	KWD 0.26	0.234	0.286
Lisinopril 5 mg	KWD 0.03	0.027	0.033
Lisinopril 10 mg	KWD 0.06	0.054	0.066
Lisinopril 20 mg	KWD 0.10	0.09	0.11
Telmisartan 40 mg	KWD 0.13	0.117	0.143
Telmisartan 80 mg	KWD 0.19	0.171	0.209
Valsartan 80 mg	KWD 0.09	0.081	0.099
Valsartan 160 mg	KWD 0.10	0.09	0.11
Spironolactone 25 mg	KWD 0.06	0.054	0.066
Spironolactone 100 mg	KWD 0.17	0.153	0.187
Eplerenone 25 mg	KWD 0.80	0.72	0.88
Eplerenone 50 mg	KWD 0.80	0.72	0.88
CBC	KWD 2.00	1.8	2.2
Darbepoetin alfa 100 mcg/0.5 ml	KWD 76.77	69.093	84.447
Sevelamer 800 mg	KWD 0.27	0.243	0.297
Calcium carbonate + vit. D tablet	KWD 0.05	0.045	0.055
Normal saline	KWD 0.51	0.459	0.56
Carvedilol 6.25 mg	KWD 0.06	0.054	0.066
Empagliflozin 10 mg	KWD 0.40	0.36	0.44
Hemodialysis session	KWD 18.00	16.2	19.8
Heparin 5,000 iu/ml −5 ml	KWD 0.04	0.0333	0.0407
LFT	KWD 4.50	4.05	4.95
Lipid profile	KWD 5.00	4.5	5.5
Prednisone 5 mg	KWD 0.02	0.018	0.022
MPA 250 mg	KWD 0.24	0.216	0.264
MPA 500 mg	KWD 0.49	0.441	0.539
Cyclosporine 100 mg	KWD 1.30	1.17	1.43
Tacrolimus 1 mg	KWD 1.90	1.71	2.09
Trough level	KWD 10.00	9	11
Kidney transplantation cost	KWD 75.00	67.5	82.5
ECHO	KWD 40.00	36	44
Myoview stress test	KWD 50.00	45	55
Pulmonary function testing	KWD 30.00	27	33
Abdominal and pelvic ultrasonography	KWD 40.00	36	44
Upper GIT endoscopy	KWD 50.00	45	55
ABO	KWD 5.00	4.5	5.5
Virology scan	KWD 61.00	54.9	67.1

Abbreviations. SZC, Sodium zirconium cyclosilicate; SPS, Sodium polystyrene sulfonate; ER, emergency room; ECG, electrocardiogram; D50W, 50% dextrose solution; CBC, complete blood count; LFT, Liver function test; ECHO, echocardiogram; ABO, Blood Grouping System; MPA, Mycophenolic acid.

Table 4. Model results at serum K+ ≥ 5.1.

Treatment Strategy	Total Cost (KWD)	Difference in Cost (KWD)	Total QALYs	Difference in QALYs	Total LYs	Difference in LYs	ICER	Interpretation
A. CKD cohort (without RRT), one-off administration of SZC/patiromer
SZC	KWD 11,210	KWD −60	4.634	0.009	7.036	0.014	Dominant	SZC generates a better QALY/LY when compared to patiromer in addition of being a cost saving
Patiromer	KWD 11,270		4.625		7.022
A. CKD cohort (without RRT), repeated administration of SZC/patiromer
SZC	KWD 13,857	KWD −1,235	4.769	0.097	7.246	0.161	Dominant	SZC generates a better QALY/LY when com-pared to patiromer in addition of being a cost saving
Patiromer	KWD 15,092		4.672		7.085
A. CKD cohort (with RRT), one-off administration of SZC/patiromer
SZC	KWD 13,219	KWD – 99	4.733	0.007	7.309	0.009	Dominant	SZC generates a better QALY/LY when com-pared to patiromer in addition of being a cost saving
Patiromer	KWD 13,318		4.726		7.300
A. CKD cohort (with RRT), repeated administration of SZC/patiromer
SZC	KWD 15,841	KWD −1,074	4.867	0.105	7.516	0.183	Dominant	SZC generates a better QALY/LY when com-pared to patiromer in adition of being a cost saving
Patiromer	KWD 16,915		4.762		7.333
A. HF cohort, repeated administration of SZC/patiromer
SZC	KWD 3,887	KWD −583	2.330	0.099	4.061	0.177	Dominant	SZC generates a better QALY/LY when com-pared to patiromer in addition of being a cost saving
Patiromer	KWD 4470		2.231		3.884
A. HF cohort, one-off administration of SZC/patiromer
SZC	KWD 2,537	KWD 67	2.038	0.202	3.546	0.357	KWD 331/QALY	Compared to patiromer, SZC is a cost-effective option
Patiromer	KWD 2,470		1.836		3.189

Abbreviations. KWD, Kuwaiti Dinar; QALYs, Quality Adjusted Life Years; ICER, Incremental Cost Effectiveness Ratio; LYs, life years; CKD, chronic kidney disease; HF, heart failure; RRT, renal replacement therapy; SZC, Sodium zirconium cyclosilicate.

Figure 2. One way sensitivity analysis of the repeated administration of SZC versus patiromer in CKD patients at serum K+ ≥ 5.1 mmol/L.

Table 5. Threshold analysis for the most influential parameters in the repeated administration of SZC versus patiromer in CKD patients at serum K+ ≥ 5.1 mmol/L.

Most influential Parameters	Base case value	Cut-off point	ICER	Interpretation
Long-term post-discontinuation management cost	KWD 15	KWD 1000	144,395	Conclusion changed^a
Baseline eGFR (ml/min/1.73m2)	47	51.7	−16,390	Conclusion did not change (cost saving)
CKD Annual eGFR decline - No RAASi	3.52	3.87	−14,160	Conclusion did not change (cost saving)
Health state utility: CKD 4	0.85	0.77	−13,491	Conclusion did not change (cost saving)

^a The cost-effectiveness threshold for Kuwait (three × GDP per capita; KWD 37,743).

Figure 3. Cost-effectiveness plane of the one-off administration of SZC versus patiromer in HF patients at serum K+ ≥ 5.1 mmol/L.

Figure 4. Cost-effectiveness acceptability curve of the one-off administration of SZC versus patiromer in HF patients at serum K+ ≥ 5.1 mmol/L.

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