Cost-effectiveness of antithrombotic agents for atrial fibrillation in older adults at risk for falls: a mathematical modelling study

Eric K.C. Wong; Christina Belza; David M.J. Naimark; Sharon E. Straus; Harindra C. Wijeysundera

doi:10.9778/cmajo.20200107

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Figure 1:
Average cost-effectiveness plane. Medications that were lower in cost and higher in effectiveness were more cost-effective. Warfarin was dominated by extension (beige line) by the combination of apixaban and acetylsalicylic acid (ASA). Note: QALY = quality-adjusted life year.
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Figure 2:
Cost-effectiveness acceptability curve for all antithrombotics. The proportion of model iterations in which the drug was most cost-effective reflects residual uncertainty in the model results. Note: ASA = acetylsalicylic acid, QALY = quality-adjusted life year.

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Table 1:
Baseline characteristics simulated in the health state transition model
Characteristic Value
Age, mean ± SD, yr 78.3 ± 5.1
Female sex, % 51
HAS-BLED^†
CHADS^* Low < 3 High ≥ 3
Low < 3 0.58 0.19
High ≥ 3 0.12 0.11
Note: CHADS = congestive heart failure, hypertension, age ≥ 75 yr, diabetes, stroke; HAS-BLED = hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly (age > 65 yr), drugs or alcohol (≥ 8 drinks/wk); SD = standard deviation.
↵* Stroke risk score.
↵† Bleeding risk score.

Table 2:

Probabilities, costs and utilities for the decision model

Variable	Estimate (range)	Distribution
Probability
First fall	0.32 (0.27 to 0.37)	β (14)
Subsequent fall	0.58 (0.39 to 0.97)	β (14)
HR bleed after a fall	1.39 (1.05 to 1.84)	Lognormal (24)
Any bleed
HAS-BLED score high, annual	0.166 (0.111 to 0.221)	β (13)
HAS-BLED score low, annual	0.091 (0.061 to 0.121)	β (13)
Major bleed given any bleed	0.31 (0.25 to 0.46)	β (25)
Intracranial bleed given major bleed	0.21 (0.14 to 0.28)	β (26)
Bed-bound after intracranial bleed (modified Rankin Scale score ≥ 5)	0.176 (0.117 to 0.235)	β (27)
Any stroke
High CHADS score	0.037 (0.025 to 0.049)	Lognormal (28)
Low CHADS score	0.083 (0.055 to 0.111)	Lognormal (28)
Major stroke given stroke	0.41 (0.20 to 0.61)	β (29)
Bed-bound after major stroke (modified Rankin Scale score ≥ 5)	0.176 (0.117 to 0.235)	β (30)
OR death due to atrial fibrillation	1.6 (1.2 to 2.2)	Lognormal (31)
HR death after major stroke	5.29 (3.53 to 7.93)	Lognormal (32)
HR death after major bleed	3.35 (2.12 to 5.27)	Lognormal (32)
HR death given bed-bound	3.81 (3.37 to 4.31)	Lognormal (33)
Cost^*
Fall, single event	7286.01 (5464.51 to 9107.51)	γ (34)
Major bleed, initial event	5358.98 (3572.64 to 7145.28)	γ (35)
Major bleed, monthly	6942.54 (4627.99 to 9255.99)	γ (35)
Minor bleed, single event	84.38 (55.89 to 111.78)	γ (35)
Major stroke, initial event	7227.47 (3613.74 to 14 441.79)	γ (35)
Major stroke, monthly	6476.51 (4384.7 to 8768.31)	γ (35)
Minor stroke, single event	3613.74 (500.15 to 7227.47)	γ (35)
Bed-bound (long-term care assumed)	4304.91 (2869.94 to 5739.88)	γ (36)
Utility/disutility
Atrial fibrillation	0.95 (0.93 to 0.98)	β (37)
Fall, per event^†	−0.11 (−0.08 to 0.14)	β (38)
Major bleed, long-term	0.60 (0.40 to 0.80)	β (39)
Minor bleed, 1 mo^†	−0.13 (−0.08 to −0.13)	β (39)
Major stroke, first year	0.26 (0.20 to 0.50)	β (39)
Major stroke, long-term	0.71 (0.40 to 0.96)	β (39)
Minor stroke, first year^†	−0.25 (−0.15 to −0.25)	β (39)
Bed-bound (modified Rankin Scale score ≥ 5)	0.14 (−0.01 to 0.29)	β (37)

Note: CHADS = congestive heart failure, hypertension, age ≥ 75 yr, diabetes, stroke; HAS-BLED = hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly (age > 65), drugs or alcohol (≥ 8 drinks/wk); HR = hazard ratio; OR = odds ratio.
↵* In 2018 Canadian dollars.
↵† Disutilities.

Table 3:

Efficacy and cost variables for antithrombotic medications compared to warfarin

Medication	Event; OR (95% CI)			Cost per month, $^*
Medication	Any bleed	Any stroke	Death	Cost per month, $^*
Acetylsalicylic acid (9)	0.59 (0.45 to 0.77)	1.88 (1.40 to 2.51)	1.04 (0.88 to 1.33)	1.02
Apixaban (9)	0.67 (0.60 to 0.75)	0.79 (0.66 to 0.94)	0.88 (0.79 to 0.98)	98.02
Dabigatran, 150 mg (9)	1.56 (0.50 to 5.74)	0.65 (0.52 to 0.81)	0.88 (0.77 to 1.01)	100.32
Dabigatran, 110 mg (9)	0.80 (0.69 to 0.93)	0.90 (0.74 to 1.10)	0.91 (0.80 to 1.04)	100.32
Edoxaban, 60 mg (9)	0.84 (0.77 to 0.90)	0.86 (0.74 to 1.01)	0.86 (0.82 to 1.01)	85.20
Edoxaban, 30 mg (9)	0.59 (0.54 to 0.64)	1.13 (0.97 to 1.32)	0.86 (0.78 to 0.96)	85.20
Rivaroxaban (9)	1.03 (0.95 to 1.11)	0.88 (0.74 to 1.03)	0.83 (0.69 to 1.00)	86.10
Warfarin	1.00	1.00	1.00	39.45^‡
Off medication^†	0.77 (0.34 to 1.20)	1.47 (1.29 to 1.65)	3.03 (2.79 to 3.27)	–

Note: CI = confidence interval, OR = odds ratio.
↵* In 2018 Canadian dollars.
↵† Relative risk (95% CI). (3)
↵‡ Including cost of monitoring therapy. (41)

Table 4:

Cost-effectiveness of the antithrombotic medications

Drug	Mean (95% credible interval)					Cost-effectiveness^†
Drug	Cost, $^*	Δ Cost	QALY	Δ QALY	ICER	Cost-effectiveness^†
Acetylsalicylic acid	83 834 (83 427 to 84 241)	–	4.89 (4.88 to 4.90)	–	–	–
Warfarin	88 704 (88 268 to 89 140)	4870 (4274 to 5466)	5.11 (5.10 to 5.12)	0.21 (0.21 to 0.23)	–	Dominated by extension
Apixaban, 5 mg	92 056 (91 639 to 92 473)	3352 (2749 to 3955)	5.86 (5.85 to 5.86)	0.74 (0.74 to 0.76)	8517 (7915 to 9121)	Cost-effective
Edoxaban, 30 mg	93 262 (92 849 to 93 675)	1206 (620 to 1792)	5.80 (5.79 to 5.81)	−0.06 (−0.07 to −0.05)	–	Absolutely dominated
Dabigatran, 110 mg	94 670 (94 234 to 95 106)	2614 (2011 to 3217)	5.56 (5.56 to 5.57)	−0.29 (−0.30 to −0.28)	–	Absolutely dominated
Edoxaban, 60 mg	97 929 (97 479 to 98 379)	5872 (5260 to 6486)	5.68 (5.68 to 5.69)	−0.17 (−0.18 to −0.16)	–	Absolutely dominated
Rivaroxaban, 20 mg	107 425 (106 892 to 107 958)	15 369 (14 692 to 16 046)	5.57 (5.56 to 5.57)	−0.29 (−0.30 to −0.28)	–	Absolutely dominated
Dabigatran, 150 mg	114 818 (114 159 to 115 477)	22 761 (21 982 to 23 542)	5.05 (5.04 to 5.06)	−0.80 (−0.82 to −0.79)	–	Absolutely dominated

Note: ICER = incremental cost-effectiveness ratio, QALY = quality-adjusted life year.
↵* In 2018 Canadian dollars.
↵† Warfarin is dominated by extension by the combination of acetylsalicylic acid and apixaban, whereas edoxaban, rivaroxaban and dabigatran are absolutely dominated by apixaban.

Table 5:

Life years and secondary outcomes from the model

Drug	Mean (95% credible interval)
Drug	Life years^*	Life expectancy, yr	Major stroke, cumulative %	Major bleed, cumulative %	Time off medication per patient, mo	Bed-bound, cumulative %
Acetylsalicylic acid	6.25 (6.24 to 6.26)	84.4 (84.4 to 84.5)	26.9 (26.7 to 27.0)	14.2 (14.1 to 14.2)	1.12 (1.12 to 1.13)	5.2 (5.2 to 5.3)
Warfarin	6.61 (6.60 to 6.62)	84.7 (84.7 to 84.7)	14.4 (14.4 to 14.5)	25.5 (25.4 to 25.5)	2.04 (2.03 to 2.04)	3.2 (3.2 to 3.2)
Apixaban, 5 mg	7.36 (7.35 to 7.37)	85.5 (85.5 to 85.5)	12.9 (12.9 to 13.1)	19.4 (19.4 to 19.5)	1.57 (1.56 to 1.57)	2.7 (2.7 to 2.7)
Edoxaban, 30 mg	7.30 (7.29 to 7.30)	85.4 (85.4 to 85.4)	18.4 (18.4 to 18.5)	16.5 (16.5 to 16.6)	1.32 (1.32 to 1.33)	4.0 (4.0 to 4.0)
Dabigatran, 110 mg	7.09 (7.09 to 7.10)	85.2 (85.2 to 85.2)	14.1 (14.1 to 14.2)	21.9 (21.9 to 22.0)	1.77 (1.76 to 1.77)	3.0 (3.0 to 3.0)
Edoxaban, 60 mg	7.28 (7.28 to 7.29)	85.4 (85.4 to 85.4)	13.8 (13.8 to 13.9)	23.6 (23.6 to 29.3)	1.91 (1.90 to 1.91)	2.9 (2.9 to 2.9)
Rivaroxaban, 20 mg	7.30 (7.29 to 7.31)	85.4 (85.4 to 85.4)	14.1 (14.1 to 14.3)	29.2 (29.2 to 29.3)	2.36 (2.35 to 2.37)	3.0 (3.0 to 3.0)
Dabigatran, 150 mg	6.91 (6.90 to 6.92)	85.0 (84.9 to 85.0)	9.8 (9.7 to 9.8)	42.7 (42.5 to 43.0)	3.45 (3.43 to 3.47)	2.3 (2.2 to 2.3)