Impact of non-adherence to direct oral anticoagulants amongst Swedish patients with non-valvular atrial fibrillation: results from a real-world cost-utility analysis

Figures & data

Figure 1. Model structure (cycle length duration: 3 months; time horizon: 20 years; baseline age of entry: 77 years old).

Table 1. Summary of model definitions for adherence and persistence.

Measure	Definition
Adherence	Based on the medication MPR and calculated only for persistent DOAC users, based on refills At each 3-month (1st year) and 6-month (thereafter) intervals, the number of days a DOAC was available was divided by the number of days in the interval MPRs were categorized as >95%, 95–91%, 90–81%, 80–71%, 70–61%, and <61% Full adherence was defined as an MPR >95%
Persistence	Patients who claimed a new DOAC prescription within 91 days after the calculated end of supply from a prior prescription If patients had the same DOAC available from a previous prescription before claiming a new prescription, the additional days theoretically covered were added to their new prescription
Complete non-persistence	Non-persistent after the first 3 months and remain so for the remainder of the time horizon in the model Not on any DOAC or other oral anticoagulant treatments in that time period

Abbreviations. DOAC, direct oral anti-coagulant; MPR, medication possession rate.

Table 2. Summary of model clinical inputs.

Description	Subgroup	Input value	Reference
Population	Gender (female)	46.0%	Komen et al. (2021)^14
	Age (years, mean)	77.0
IS/ICH proportions	Minor IS (out of total IS)	41%*	Bowrin et al. (2020)^12
	Minor ICH (out of total ICH)	40.0%	Assumption
Mortality risk	General mortality	N/A	Sweden life tables (2019)
	Death from acute IS	17.60%	Komen et al. (2021)^15
	Death from post IS	8.12%	Bowrin et al. (2020)^12
	Death from acute ICH	31.6%	Komen et al. (2021)^15
	Death from post ICH	14.11%	Bowrin et al. (2020)^12
Age HR	IS event	1.03	Pennlert et al. (2014)^16
Event risk (OR)	Non-persistent	2.05	Komen et al. (2020)^14
	Non-adherence per level (linear)	1.43
	MPR 91–95% (aOR)	0.85
	MPR 81–90% (aOR)	1.53
	MPR 71–80% (aOR)	3.18
	MPR 61–70% (aOR)	2.09
	MPR <61% (aOR)	2.85
	ICH risk	1.00	Assumption
	GI bleed	1.923^†	Bowrin et al. (2020)^12

Abbreviations. a, adjusted; GI, gastrointestinal; HR, hazard ratio; IS, ischemic stroke; ICH, intracranial hemorrhage; MPR, medication possession rate; OR, odds ratio.

*Proportion calculated from 3-month probabilities (apixaban arm) for minor and major IS.

^†Hazard ratio for VKA vs. apixaban (1/0.52).

Table 3. Summary of model cost inputs.

Description	Subgroup	Input value (SEK, 2021)	Reference
Acute IS	Acute treatment − 1 cycle	1000,213.00^‡	Lanitis et al. (2014)^3
Post IS	Maintenance management (minor) – monthly costs	1,383.00^‡
	Maintenance management (major) – monthly costs	24,293.00^‡
Acute ICH	Acute treatment − 1 cycle	1000,213.00^‡
Post ICH	Maintenance management (mild/moderate) – monthly costs	1,383.00^‡
	Severe – monthly costs	24,293.00^‡
GI bleed	Non-complicated − 1 cycle	8,766.00	Socialstyrelsen (National Board of Health and Welfare)
Drug cost	Apixaban − 1 cycle	20.27^‡	Lanitis et al. (2014)^3

Abbreviations. GI, gastrointestinal; HR, hazard ratio; IS, ischemic stroke; ICH, intracranial hemorrhage.

^‡Cost adjusted by Sweden Consumer Price Index, https://bit.ly/2TD1wxT.

Table 4. Summary of model utility values.

Health state	Subgroup	Utility	Reference
Stable AF	70–79	0.794	Aronsson et al. (2017)^17
	80–89	0.733
IS	Acute minor IS	0.730	Luengo-Fernandez et al. (2013)^18
	Acute major IS	0.410
	Post IS	0.650	Lindgren et al. (2008)^19
	(3 months)
	Post IS	0.750
	(6 months)
	Post IS	0.630
	(9 months)
	Post IS	0.670
	(12 months)
ICH	Primary ICH	0.560	Luengo-Fernandez et al. (2013)^18
	(1 month; acute)
	Primary ICH	0.650
	(6 months; post-ICH)
	Primary ICH	0.670
	(12 months; post-ICH)
GI bleed	Disutility (1 cycle)	−0.010	Assumption

Abbreviations. AF, atrial fibrillation; IS, ischemic stroke; ICH, intracranial hemorrhage.

Table 5. Summary of base-case results.

	Full adherence (Persistent users)	MPR 81–90%	MPR 71–80%	MPR 61–70%	MPR < 61%
Costs (SEK, discounted)
Drug costs	66,159,297	64,549,543	62,176,220	58,773,347	54,131,504
IS treatment costs	102,644,784	135,956,738	175,248,138	218,536,937	262,693,399
ICH treatment costs	14,689,918	13,847,880	12,762,761	11,428,105	9,890,911
GI bleed costs	614,671	601,596	582,344	554,762	517,158
Total costs	182,864,303	213,626,985	249,320,224	287,672,124	325,367,262
Health outcomes (discounted)
Total LYs	8,183.95	8,007.24	7,747.01	7,374.21	6,865.95
Total QALYs	6,115.42	5,972.78	5,765.94	5,473.80	5,080.07
Cases of IS	235.05	351.78	524.47	770.77	1,101.45
Cases of ICH	40.13	40.75	41.22	41.26	40.55
Cases of GI bleed	82.73	80.72	77.77	73.58	67.91
Incremental results (vs. full adherence)
Increase in total costs (SEK)	—	30,762,682	66,455,921	104,807,821	142,502,959
Additional IS cases	—	116.73	289.42	535.71	866.40
LYs lost	—	176.71	436.94	809.74	1,318.00
QALYs lost	—	142.64	349.49	641.62	1,035.36

Abbreviations. GI, gastrointestinal bleed; ICER, incremental cost-effectiveness ratio; IS, ischemic stroke; ICH, intracranial hemorrhage; LY, life-year; MPR, medication possession rate; QALY, quality adjusted life year.

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Data availability statement

The data underlying this article are available at https://academic.oup.com/ehjcvp/article/7/FI1/f72/5824225?login=false.