Cost-Effectiveness of Apixaban versus Other Direct Oral Anticoagulants and Warfarin in the Prevention of Thromboembolic Complications Among Finnish Patients with Non-Valvular Atrial Fibrillation

Figures & data

Figure 1 Schematic presentation of the model. *Mild, moderate or severe, #transient state (ie, the patients transit back to the previous health state after one cycle and either continue or discontinue anticoagulation treatment). Reproduced from Hallinen T, Soini EJ, Linna M, Saarni SI. Cost-effectiveness of apixaban and warfarin in the prevention of thromboembolic complications among atrial fibrillation patients. Springerplus. 2016;5(1):1354, under the terms of the creative commons attribution 4.0 international license (http://creativecommons.org/licenses/by/4.0/).¹⁸

Table 1 Risk of Modeled Health Events According to Treatment

	Rate per 100 Patient Years		Hazard Ratio (95% CI) vs Apixaban
	Apixaban	No Treatment^Citation26	Warfarin	Dabigatran	Rivaroxaban
Stroke^a	1.359^b	4.186	1.67 (1.54–1.79)^Citation7	1.08 (0.90–1.28)^Citation7	0.95 (0.87–1.03)^Citation7
Intracranial hemorrhage	0.249^b	0	2.38 (2.08–2.70)^Citation7	1.02 (0.62–1.68)^Citation7	1.15 (0.99–1.33)^Citation7
Other major bleed	1.603^c	0	2.33 (2.17–2.50)^Citation7	1.08 (0.93–1.24)^Citation7	1.49 (1.39–1.59)^Citation7
Clinically relevant non-major bleed	2.090^d	0	1.433 (1.241–1.655)^d	1.00 (0.900–1.100)^Citation34	1.52 (1.28–1.80)^Citation34
Myocardial infarction	1.654^e	1.003	1.149^Citation3	1.460 (0.960–2.200)^Citation34	1.060 (0.730–1.520)^Citation34
Systemic embolism^a	0.060^f	0.956	1.67 (1.54–1.79)^Citation7	1.08 (0.90–1.28)^Citation7	0.95 (0.87–1.03)^Citation7
Other CV hospitalizations^g	10.46	16.506	1.00	1.00	1.00
Treatment discontinuation for non-event related reasons	13.107^d		1.10 (1.04–1.16)^d	1.50 (1.36–1.67)^Citation34	1.18 (1.08–1.61)^Citation34

Notes: ^aAssumed equal to stroke and systemic embolism. ^bTotal number of events among 16,741 Finnish AF patients using warfarin were 375 for stroke and 99 for ICH.³¹ Assuming a full follow-up of one year for each patient, these were converted to a rate per 100 patient-years: 2.27 and 0.59, respectively. ^cTotal number of bleeding events in 125,261 Finnish patients using warfarin was 5412,³² and the corresponding rate was 4.32 per 100 patient-years. By subtracting the ICH rate from total bleeds, the rate for other major bleeds was estimated at 3.73 per 100 patient-years. ^dSecondary analysis of ARISTOTLE-trial. ^e1.900 per 100 patient-years for warfarin.³³ f0.1 per 100 patient-years for warfarin.⁸ gSecondary analysis of AVERROES-trial, all treatments assumed equal.

Table 2 Costs and Quality of Life Inputs

	Cost^b	Utility
Drug cost per day^a
Apixaban 2.5 or 5 mg, twice a day	2.53
Dabigatran 110 or 150 mg, twice a day	2.58
Rivaroxaban 20 mg, once a day	2.59
Warfarin 5 mg	0.10
Routine care & Monitoring
General physician visit	119.97^Citation35
INR-monitoring, warfarin only (Nurse visit and INR-test)	64.85^Citation35,Citation36
Laboratory tests^c	13.20^Citation36
Health states/Events^Citation18
AF		0.743
Ischemic stroke
Mild		−0.087
Acute Care	4543.12
Long-term Maintenance	0
Moderate		−0.198
Acute Care	7719.71
Long-term Maintenance	967.57
Severe		−0.644
Acute Care	7725.75
Long-term Maintenance	4403.61
Fatal	5475.59
Hemorrhagic Stroke
Mild		−0.071
Acute Care	2696.51
Long-term Maintenance	2696.51
Moderate		−0.352
Acute Care	9455.08
Long-term Maintenance	2183.41
Severe		−0.578
Acute Care	9641.27
Long-term Maintenance	3818.62
Fatal	5708.06
Systemic Embolism		−0.084
Acute Care	2125.68
Long-term Maintenance	106.76
Other ICH (excluding hemorrhagic stroke)	4366.50	−0.168
Other Major Bleeds (excluding ICH)		−0.168
GI Bleeds	3537.48
Non-ICH and Non-GI Related Major Bleeds	3537.48
CRNM Bleeds	2058.10	−0.0582
MI		−0.005
Acute Care	5453.00
Long-term Maintenance	538.50
Other CV Hospitalization	3774.93
Adverse events
Dyspepsia^d	125.49

Notes: ^aDrug costs were assessed based on the cost of the reimbursed price of the pack with approximately one-month supply for each product in 2/2021.³⁷ bConversion from previous years (to year 2019 real values) were made using the communal health care price index by statistics Finland.³⁸ cBasic blood count, thrombocytes, creatinine, estimated glomerular filtration rate, alanine aminotransferase.³⁹ dAssumption: GP visit, pantoprazole 20 mg 100 tablets. The proportion of patients experiencing dyspepsia was obtained from the respective clinical trials and were 1.7% for apixaban and rivaroxaban, 3.5% for dabigatran, and 1.8% for warfarin.

Table 3 Results of the Cost-Effectiveness Analysis

	LY	QALY	Costs				Difference, Apixaban vs Comparator			ICER (€/QALY)
			Total	Monitoring	Event	Drug	Cost	LY	QALY
Apixaban	8.37	6.09	18,342	1068	13,356	3918
Rivaroxaban	8.32	6.05	18,385	1057	13,703	3625	−43	0.05	0.03	Apixaban dominates
Dabigatran	8.23	5.98	18,746	1046	14,588	3112	−404	0.13	0.11	Apixaban dominates
Warfarin	8.22	5.94	22,033	5877	16,008	149	−3691	0.15	0.14	Apixaban dominates

Figure 2 The cost-effectiveness plane for apixaban versus (A) warfarin, (B) dabigatran and (C) rivaroxaban. Green line depicts ICER threshold of 35,000 euros per QALY gained. The points lying below the line represent the simulations where apixaban was either cost-effective or dominating (South-West quadrant) versus its comparator.

Figure 3 The cost-effectiveness acceptability curve for apixaban versus warfarin, dabigatran and rivaroxaban.

Table 4 Results of the Deterministic Sensitivity Analyses

Scenario	Treatment	QALY	Costs	Net Cost	Net QALY	ICER (€/QALY), Apixaban vs Comparator
No discounting	Apixaban	7.34	22,511
	Rivaroxaban	7.30	22,553	−42	0.04	Apixaban dominates
	Dabigatran	7.20	22,951	−440	0.14	Apixaban dominates
	Warfarin	7.15	26,769	−4257	0.19	Apixaban dominates
5-year timeframe	Apixaban	3.06	8028
	Rivaroxaban	3.05	8095	−68	0.01	Apixaban dominates
	Dabigatran	3.04	8298	−270	0.02	Apixaban dominates
	Warfarin	3.03	10,263	−2235	0.04	Apixaban dominates
Retail prices, largest available pack	Apixaban	6.09	18,342
	Rivaroxaban	6.05	18,063	279	0.03	8978
Wholesale prices, largest available pack	Apixaban	6.09	17,329
	Rivaroxaban	6.05	17,438	−109	0.03	Apixaban dominates
	Dabigatran	5.98	17,837	−507	0.11	Apixaban dominates
	Warfarin	5.94	21,987	−4658	0.14	Apixaban dominates
Warfarin monitoring cost reduced^a	Apixaban	6.09	18,342
	Warfarin	5.94	19,166	−824	0.14	Apixaban dominates

Notes: ^aPhone call, 13.08 euros, instead of a nurse visit. Dominates = more effective, less costly.

Abbreviations: AF, atrial fibrillation; DOAC, direct oral anticoagulant; GI, gastrointestinal; HS, hemorrhagic stroke; ICH, intracranial hemorrhage; ICER, incremental cost-effectiveness ratio; IS, ischemic stroke; MI, myocardial infarction; NMB, net monetary benefit; SE, systemic embolism; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life-year; WTP, willingness-to-pay.

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