Clinical and economic impact of rivaroxaban on the burden of atrial fibrillation: The case study of Japan

Figures & data

Figure 1. Markov chain. CV, cardiovascular; ECH, extracranial hemorrhage; ICH, intracerebral hemorrhage; IS, ischemic stroke; MI, myocardial infarction; SE, systemic embolism.

Table 1. Population, population growth, prevalence of NVAF and non-CV mortality, by age^2,38–41.

Age (years)	Population		AF		Non-CV mortality
	Number	Annual growth	Prevalence	NVAF
40−49	18,396,000	−1.2%	0.18%	76%	0.1%
50−59	15,429,000	+1.5%	0.49%	74%	0.3%
60−69	18,128,000	−2.4%	1.68%	84%	0.6%
70−79	14,183,000	+1.5%	4.29%	84%	1.5%
≥80	9,737,000	+3.1%	6.68%	81%	7.0%

AF, atrial fibrillation; CV, cardiovascular; NVAF, non-valvular atrial fibrillation.

Figure 2. Eligible patient population. AF, Atrial fibrillation; CHADS₂, Congestive heart failure, Hypertension, Age (≥75 years), Diabetes Mellitus, Prior Stroke or TIA; NVAF, Non-valvular atrial fibrillation.

Table 2. Treatment patterns^26–28.

	CHADS2 score	Rivaroxaban	No treatment	Aspirin	VKA
					Well-controlled	Poorly-controlled
Treatment pattern before NOAC introduction	CHADS2 = 1	0%	54%	3%	26%	17%
	CHADS2 ≥ 2	0%	46%	4%	34%	16%
Perfect adherence to guidelines using rivaroxaban as an example	CHADS2 = 1	74%	0%	0%	26%	0%
	CHADS2 ≥ 2	66%	0%	0%	34%	0%

CHADS₂, Congestive heart failure, Hypertension, Age (≥75 years), Diabetes Mellitus, Prior Stroke or TIA; NOAC, Novel oral anti-coagulant; VKA, vitamin K antagonist.

Table 3. Baseline risk of events, by age^{14,31,42–44}.

Age (years)	IS		SE	MI	ICH		Major ECH
	Moderate	High			Moderate	High	Moderate	High
40−49	0.2%	1.1%	0.27%	0.1%	0.1%	5.5%	0.74%	1.68%
50−59	0.4%	2.6%		0.6%	0.1%	5.5%
60−69	1.4%	9.2%		1.4%	0.4%	6.9%
70−79	3.2%	21.7%		4.1%	0.6%	8.1%
≥80	3.2%	21.7%		4.1%	0.6%	8.8%

ECH, extracranial hemorrhage; ICH, intracranial hemorrhage; IS, ischemic stroke; MI, myocardial infarction; SE, systemic embolism.

Table 4. CV mortality associated with events^{14,31,45–47}.

	IS		SE	MI	ICH	Major ECH
	Minor	Major
Mortality rate following event	3.7%	23.1%	0.0%	22.9%	10.8%	6.7%

CV, cardiovascular; ECH, extracranial hemorrhage; ICH, intracranial hemorrhage; IS, ischemic stroke; MI, myocardial infarction; SE, systemic embolism.

Table 5. Relative risk (RR) of events (including 95% CI) compared to no treatment.

Event	No treatment	Rivaroxaban	Aspirin	VKA
IS	1.00	0.14 (0.04–0.44)	0.63 (0.36–1.08)	0.36 (0.23–0.54)
SE		0.47 (0.01–36.24)	0.47 (0.06–2.23)	0.46 (0.10–1.58)
MI		1.61 (0.10–58.87)	0.49 (0.11–1.84)	0.42 (0.11–1.36)
ICH		2.24 (0.29–22.33)	2.08 (0.46–11.26)	4.21 (0.81–31.56)
ECH		4.46 (0.23–122.59)	3.13 (0.59–24.83)	4.40 (1.21–20.33)

CI, confidence interval; ECH, extracranial hemorrhage; ICH, intracranial hemorrhage; IS, ischemic stroke; MI, myocardial infarction; RR, relative risk; SE, systemic embolism; VKA, vitamin K antagonist.

Table 6. Drug costs^50–52.

	Rivaroxaban	Aspirin	VKA
Average daily dose	1 (10/15mg)	1 (100mg)	3 (3mg)
Average daily cost	¥464.95	¥5.60	¥28.80

VKA, vitamin K antagonist.

Table 7. First and subsequent year costs^{26,48,54–57}.

Event	First year	Subsequent year	CV death
Major IS	¥4,616,921	¥4,307,905	¥1,385,992
Minor IS	¥763,271	—	¥763,271
SE	¥1,169,439	—	¥1,169,439
MI	¥2,764,925	¥1,002,192	¥2,013,281
ICH	¥4,288,283	¥3,338,187	¥1,784,642
Major ECH	¥310,759	—	¥310,759

CV, cardiovascular; ECH, extracranial hemorrhage; ICH, intracranial hemorrhage; IS, ischemic stroke; MI, myocardial infarction; SE, systemic embolism.

Figure 3. Breakdown of events experienced over the analysis time horizon. CV, cardiovascular; ECH, extracranial hemorrhage; ICH, intracranial hemorrhage; IS, ischemic stroke; MI, myocardial infarction; SE, systemic embolism.

Figure 4. Net budget impact over the analysis time horizon.

Figure 5. Breakdown of net spending over the analysis time horizon.

Figure 6. One-way sensitivity analysis. ASA, Acetylsalicylic acid; ICH, intracranial hemorrhage; IS, ischemic stroke; MI, myocardial infarction; RR, relative risk; VKA, vitamin K antagonist.

Figure 7. Budget impact over analysis time horizon, scenario analysis. AF, atrial fibrillation.

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