Cost-effectiveness of rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation in the Japanese healthcare setting

Figures & data

Figure 1. Model structure. Permanent events are boxed; transient events are non-boxed. AF: atrial fibrillation; IC: intracranial; MI: myocardial infarction; Tx: treatment.

Table 1. Case fatality and mortality rates.

Health states	%	Low value (%)	High value (%)	Source
Case fatality of a major stroke	9.9	7.4	12.4	Stroke Databank 2015^33
Case fatality of a minor stroke	0.0	0	0	Assumption
Post-major stroke mortality rate	3.5	2.6	4.4	Lip et al.^1
Post-minor stroke mortality rate	0.0	0.0	0.0	Assumption
Case fatality of major bleeding	1.6	1.2	1.9	ROCKET trial safety^9^,^34
Case fatality of minor bleeding	0.0	0.0	0.0	Assumption
Case fatality of intracranial bleeding	14.7	11.0	18.4	Stroke Databank 2015^33
Post-intracranial bleeding mortality rate	4.9	2.6	4.4	Lip et al.^1
Case fatality of SE	0.0	0	0	Assumption
Case fatality rate of MI	9.7	7.3	12.1	ROCKET trial safety^9^,^34
Post-MI mortality rate	2.7	0.0	6.8	Hoit et al.^35

MI: myocardial infarction; OR: odds ratio; SE: systemic embolism.

Table 2. Overview of drug acquisition, monitoring visits, and event treatment costs.

Event	Cost ￥ (€)	Low value	High value	Source
Acquisition
Rivaroxaban 10 or 15 mg	507.71 (€4.32) (weighted average)/day	456.939 (€3.89)	558.481 (€4.72)	Yakka search Version 3.0^25
Warfarin 0.5–5.0 mg	28.80/day (€0.24)	25.92 (€0.22)	31.68 (€0.27)	Yakka search Version 3.0^25
Aspirin 100 mg	5.6/day (€0.05)	5.04 (€0.04)	6.16 (€0.05)	Yakka search Version 3.0^25
Monitoring visits
Warfarin monitoring visit	2,150 (€18,2826)	1,935 (€16,4544)	2,365 (€20,1109)	Shirobon net^36
Check-ups for other therapy	720 (€6.12)	648 (€5.51)	792 (€6.73)	Shirobon net^36
Stroke treatment costs
Acute treatment—minor	1,014,868 (€8,628.39)	952,860 (€8,101.20)	1,078,803 (€9,172.88)	MDV claims data reported Kamae et al. (mild ischaemic stroke acute care—per episode)^27
Acute treatment—major	1,705,690 (€14,503.85)	1,600,639 (€13,610.57)	1,814, 037 (€15,424.65)	MDV claims data reported by Kamae et al. (moderate and severe ischaemic stroke acute care—per episode) that were weighted by the distribution of patients at hospital discharge reported in the stroke databank 2015 report^27
Follow-on care (per quarter)—minor	0	0	0	Assume no follow-on care for minor stroke
Follow-on care (per quarter)—moderate and major	1,023,310 (€8,700.61)	973,397 (€8,276.23)	1,074, 462 (€9,136.19)	Costs reported by Kamae et al.^27 which used data from Hattori et al.^28 (moderate and severe ischaemic stroke maintenance care per month) that were weighted by the distribution of patients at hospital discharge reported in the stroke databank 2015 report
Rehabilitation costs per day	0	0	0	Rehabilitation costs are captured in stroke treatment costs (MDV claims data reported by Kamae et al.^27)
Bleeding treatment costs
Acute treatment—minor	348,240 (€2,960.91)	313,416 (€2,665.46)	383,064 (€3,257.78)	Stroke care unit hospitalisation cost per day (stroke care unit admits patients with cerebral infarction, cerebral haemorrhage, subarachnoid haemorrhage, and other patients approved by the doctor)^36
				LoS was extracted from Takashima et al.^37, where they reported for the LoS for subarachnoid haemorrhage. The first quartile, i.e. 6 days was assumed to be representative of minor bleeds
Acute treatment—major	666,402 (€5,667.21)	562,202 (€4,779.27)	779,332 (€6,625.09)	MDV claims data reported by Kamae et al. for other major bleedings^27
Acute treatment—intracranial bleeding	2,019,872 (€17,169.83)	1,545,936 (€13,141.16)	2,557,022 (€21,733.86)	MDV claims data reported by Kamae et al.: minor = 1,448,758; moderate = 2,131,870; severe = 2,085,764^27
				Weighted average in function of the distribution of severity level based on the analysis by Sorensen et al.^38
Follow-on care (per quarter)	1,071,885 (€9,110.675)	1,012,591 (€8,606.82)	1,132,848 (€9,628.98)	Costs reported by Kamae et al.^27 which used data from Hattori et al.^28
				Mild haemorrhagic stroke chronic care (per month): 157,117
				Moderate haemorrhagic stroke chronic care (per month): 336,541
				Severe haemorrhagic stroke chronic care (per month): 383,444
				Weighted average in function of the distribution of severity level based on Sorenson 2011
Rehabilitation costs (per quarter)	0	0	0	Assumption validated by clinical experts: Dr Tanahashi recommended that the duration of rehabilitation for intracranial bleeding to be longer than 14 days. However, this duration impacts only the costs and costs were taken as aggregated values from Kamae et al.^27 Therefore, the duration of rehabilitation is not necessary
SE treatment costs
Acute treatment	1,111,879 (€9,450.04)	1,028,899 (€8,744.78)	1,194,860 (€10,154.60)	Reported by Kamae et al.^27 which used data from Tanihata et al.^39 and Evans et al.^40 for systemic embolism acute care per episode
MI treatment costs
Acute treatment	2,136,214 (€18,154.76)	1,922,573 (€16,339.25)	2,360,950 (€20,064.26)	MDV claims data reported by Kamae et al.^27 MI acute care—per episode
Follow-on care (per quarter)	0	0	232,276 (€1,973.97)	Assumption validated by clinical experts, the high value was referenced from MDV claims data of MI chronic care per month reported by Kamae et al.^27

LoS: length of stay; MI: myocardial infarction; MDV: Medical Data Vision Co Ltd; OR: odds ratio; SE: systemic embolism.

Table 3. Utility parameters.

Utility data	Mean	Low	High	Source
Anticoagulation
Stable—not on therapy	0.8305	0.7475	1.0000	Shiroiwa et al.^41
Stable—on warfarin therapy	0.8175	0.7475	0.9200	Shiroiwa et al.^41
Utility decrement used for Warfarin	0.0130	0	0.08	Dorian et al.^42; Lip et al.^43
Stable—on other therapy	0.8305	0.7475	1.0000	Shiroiwa et al.^41
Stable—initiating warfarin therapy	0.8175	0.7475	0.9200	Shiroiwa et al.^41
Utility decrement used for Initiating warfarin	0.0130	0	0.08	Assumption
Embolic events
Minor stroke	0.7840	0.7580	0.8090	Hattori and Katayama^28
Post-minor stroke	0.7840	0.7580	0.8090	Assumption—same as minor stroke
Major stroke	0.0920	0.0700	0.1170	Hattori and Katayama^28
Post-major stroke	0.5066	0.4559	0.9136	Hallan^44
SE	0.6270	0.5890	0.6640	Hattori and Katayama^28
Bleeding events
Minor bleeding	0.7725	0.7345	0.8015	Dorian et al.^42; Lip et al.^43
Major bleeding	0.6665	0.5925	0.7495	Dorian et al.^42; Lip et al.^43
Intracranial bleeding	0.6795	0.5925	0.7495	Dorian et al.^42; Lip et al.^43
Post-intracranial bleeding	0.5066	0.4559	0.9136	Assumption as post major stroke
Myocardial infarction
MI	0.2205	0.1985	0.2426	Dorian et al.^42; Lip et al.^43
Post-MI	0.7308	0.6578	0.8039	Sanders et al.^45

MI: myocardial infarction; OR: odds ratio; SE: systemic embolism.

Table 4. Results of cost-effectiveness analysis.

	Base case			Scenario analysis
	Rivaroxaban	Warfarin	Difference	Rivaroxaban	Warfarin	Difference
Total costs, ¥ (€)	¥6,754,603 (€57,442.22)	¥6,873,496 (€58,456.27)	−¥118,892 (€1,011.11)	¥7,680,947 (€65,319.27)	¥6,854,783 (€58,293.52)	¥826,164 (€7,025.90)
Total QALYs	10.03	9.50	0.535	9.79	9.50	0.288
Total LY	12.63	12.20	0.429	12.44	12.21	0.230
Total ISs	0.58	0.87	0.284	0.79	0.86	0.072
Total bleedings	1.27	1.10	−0.170	1.20	1.11	−0.094
Total MI	0.05	0.02	−0.03	0.02	0.02	0
ICER, ¥ (€) (per QALY)			Dominant			¥2,873,499 (€24,440.31)

ICER: incremental cost-effectiveness ratio; IS: ischaemic stroke; LY: life-years; QALY: quality-adjusted life-years.

Figure 2. Results of one-way sensitivity analysis (Tornado diagrams). AF: atrial fibrillation; IC: intracranial; MI: myocardial infarction; RR: relative risk; SE: systemic embolism.

Figure 3. Cost-effectiveness plane.

Figure 4. Cost-effectiveness acceptability curve based on QALY.

Table 5. Results of the network meta-analysis (treatment effect data for base case analysis and scenario analysis).

	Baseline event risk (%)	Low value (%)	High value (%)	OR [95% CI] of warfarin vs. placebo (base case and scenario)	OR [95% CI] of rivaroxaban vs. placebo (base case and scenario)
IS	1.40	0.85	2.18	0.36 [0.23, 0.54] 0.36 [0.23, 0.56]	0.14 [0.04, 0.44] 0.28 [0.12, 0.56]
MI	0.07	0.01	0.33	0.42 [0.11, 1.36] 0.43 [0.12, 1.36]	1.61 [0.1, 58.87] 0.38 [0.09, 1.89]
SE	0.07	0.01	0.30	0.46 [0.1, 1.58] 0.47 [0.1, 1.65]	0.47 [0.01, 36.24] 0.13 [0.01, 1.28]
Major extracranial bleeding	0.03	0.01	0.08	3.62 [1.16, 12.96] 3.59 [1.3, 10.77]	3.1 [0.17, 56.72] 3.42 [0.49, 28.05]
Minor extracranial bleeding	0.72	0.95	1.42	4.4 [1.21, 20.33] 4.4 [1.4, 17.57]	4.46 [0.23, 122.59] 4.78 [0.43, 49.65]
Intracranial bleeding	0.07	0.04	0.13	4.21 [0.81, 31.56] 4.22 [0.82, 31.37]	2.24 [0.29, 22.33] 2.71 [0.51, 20.68]

95% CI: 95% confidence interals; IS: ischaemic stroke; MI: myocardial infarction; OR: odds ratio; SE: systemic embolism.

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