Background
Methods
Decision analytical model
Model
Model parameters
Variable | Base-Case | Range | References | |
---|---|---|---|---|
Stroke | ||||
Annual rate of ischemic stroke, % | ||||
Aspirin alone | 2 · 80 | 2 · 80 | 4 · 50 | |
Clopidogrel plus aspirin | 1 · 90 | 1 · 69 | 2 · 11 | [2] |
Warfarin | 1 · 21 | 1 · 05 | 1 · 42 | |
Dabigatran, 110 mg | 1 · 34 | 1 · 31 | 1 · 55 | |
Dabigatran, 150 mg | 0 · 92 | 0 · 75 | 1 · 09 | |
Apixaban | 0 · 97 | 0 · 78 | 1 · 19 | |
Rivaroxaban | 1 · 34 | 1 · 07 | 1 · 66 | |
LAA | 0 · 84 | 0 · 40 | 1 · 10 | |
Ischemic stroke with clopidogrel plus aspirin or aspirin alone, % | ||||
Fatal (within 30 days) | 17 · 90 | 10 · 10 | 17 · 90 | [17] |
Moderate to severe neurologic sequelae | 30 · 00 | 30 · 00 | 41 · 70 | [17] |
Mild neurologic sequelae | 41 · 00 | 34 · 80 | 41 · 00 | [17] |
No residual neurologic sequelae | 11 · 00 | 11 · 00 | 13 · 30 | [17] |
Ischemic stroke with warfarin, dabigatran, apixaban, rivaroxaban or LAA, % | ||||
Fatal (within 30 days) | 8 · 20 | 5 · 50 | 10 · 90 | |
Moderate to severe neurologic sequelae | 40 · 20 | 35 · 30 | 45 · 10 | |
Mild neurologic sequelae | 42 · 50 | 37 · 60 | 47 · 40 | |
No residual neurologic sequelae | 9 · 10 | 6 · 20 | 12 · 00 | |
Annual rate of TIA, % | 28 · 00 | 25 · 00 | 33 · 00 | |
Hemorrhage | ||||
Annual rate of minor hemorrhage, % | ||||
Aspirin alone | 1 · 40 | 1 · 27 | 1 · 53 | [2] |
Clopidogrel plus aspirin | 3 · 50 | 2 · 58 | 4 · 42 | [2] |
Warfarin | 18 · 63 | 11 · 40 | 25 · 80 | |
Dabigatran, 110 mg | 13 · 20 | 12 · 60 | 13 · 80 | |
Dabigatran, 150 mg | 14 · 80 | 14 · 20 | 15 · 50 | |
Apixaban | 18 · 10 | 17 · 54 | 19 · 35 | [13] |
Rivaroxaban | 11 · 80 | 10 · 94 | 12 · 88 | [4] |
LAA (45 days warfarin followed by 180 days clopidogrel and aspirin then lifetime aspirin after LAA) | 4 · 28 | 3 · 70 | 4 · 86 | Assumption |
LAA (lifetime aspirin after LAA) | 1 · 40 | 1 · 27 | 1 · 53 | Assumption |
Annual rate of major hemorrhage, % | ||||
Aspirin alone | 1 · 00 | 0 · 68 | 1 · 32 | [2] |
Clopidogrel plus aspirin | 1 · 50 | 1 · 35 | 1 · 65 | [2] |
Warfarin | 3 · 32 | 3 · 09 | 3 · 57 | |
Dabigatran, 110 mg | 2 · 87 | 2 · 50 | 3 · 32 | |
Dabigatran, 150 mg | 3 · 32 | 2 · 89 | 3 · 82 | |
Apixaban | 2 · 13 | 1 · 85 | 2 · 47 | [13] |
Rivaroxaban | 3 · 60 | 3 · 06 | 4 · 08 | [4] |
LAA (45 days warfarin followed by 180 days clopidogrel and aspirin then lifetime aspirin after LAA) | 1 · 54 | 1 · 30 | 1 · 77 | Assumption |
LAA (lifetime aspirin after LAA) | 1 · 00 | 0 · 68 | 1 · 32 | Assumption |
Annual rate of ICH, % | ||||
Aspirin alone | 0 · 20 | 0 · 19 | 0 · 21 | [2] |
Clopidogrel plus aspirin | 0 · 40 | 0 · 24 | 0 · 59 | [2] |
Warfarin | 0 · 75 | 0 · 70 | 0 · 80 | |
Dabigatran, 110 mg | 0 · 23 | 0 · 14 | 0 · 32 | |
Dabigatran, 150 mg | 0 · 30 | 0 · 20 | 0 · 40 | |
Apixaban | 0 · 33 | 0 · 24 | 0 · 46 | [13] |
Rivaroxaban | 0 · 50 | 0 · 33 | 0 · 65 | [4] |
LAA (45 days warfarin followed by 180 days clopidogrel and aspirin then lifetime aspirin after LAA) | 0 · 37 | 0 · 27 | 0 · 47 | Assumption |
LAA (lifetime aspirin after LAA) | 0 · 20 | 0 · 19 | 0 · 21 | Assumption |
Annual rate of major hemorrhage as fatal, % | ||||
Aspirin alone | 0 · 20 | 0 · 14 | 0 · 26 | [2] |
Clopidogrel plus aspirin | 0 · 30 | 0 · 19 | 0 · 51 | [2] |
Warfarin | 0 · 90 | 0 · 50 | 1 · 80 | |
Dabigatran, 110 mg | 1 · 22 | 1 · 08 | 1 · 36 | [3] |
Dabigatran, 150 mg | 1 · 45 | 1 · 33 | 1 · 56 | [3] |
Apixaban | 0 · 37 | 0 · 30 | 0 · 42 | [13] |
Rivaroxaban | 0 · 20 | 0 · 16 | 0 · 40 | [4] |
LAA (45 days warfarin followed by 180 days clopidogrel and aspirin then lifetime aspirin after LAA) | 0 · 45 | 0 · 38 | 0 · 51 | Assumption |
LAA (lifetime aspirin after LAA) | 0 · 20 | 0 · 14 | 0 · 26 | Assumption |
Myocardial infarction | ||||
Annual rate of MI, % | ||||
Aspirin alone | 0 · 90 | 0 · 77 | 1 · 03 | [2] |
Clopidogrel plus aspirin | 0 · 70 | 0 · 53 | 0 · 93 | [2] |
Warfarin | 0 · 78 | 0 · 61 | 1 · 12 | |
Dabigatran, 110 mg | 0 · 82 | 0 · 61 | 1 · 12 | |
Dabigatran, 150 mg | 0 · 81 | 0 · 60 | 1 · 09 | |
Apixaban | 0 · 53 | 0 · 40 | 0 · 71 | [13] |
Rivaroxaban | 0 · 91 | 0 · 71 | 1 · 19 | [4] |
LAA (45 days warfarin followed by 180 days clopidogrel and aspirin then lifetime aspirin after LAA) | 0 · 76 | 0 · 57 | 1 · 00 | Assumption |
LAA (lifetime aspirin after LAA) | 0 · 90 | 0 · 77 | 1 · 03 | Assumption |
Pericardial Effusions, % | ||||
Rate of Pericardial effusions | ||||
LAA (within 7 days) | 2 · 07 | 1 · 50 | 2 · 40 | |
Success implantation, % | ||||
Rate of LAA device implanted after discontinuing warfarin | 0.868 | 0.8342 | 0.9018 | [18] |
Hospitalization | ||||
Annual rate of Hospitalization, % | ||||
Warfarin | 20 · 80 | 15 · 5 | 26 · 10 | [3] |
Dabigatran, 110 mg | 19 · 40 | 13 · 49 | 25 · 32 | [3] |
Dabigatran, 150 mg | 20 · 20 | 19 · 94 | 20 · 46 | [3] |
Apixaban | 20 · 80 | 15 · 50 | 26 · 10 | Assumed equal to Wafarin |
Rivaroxaban | 20 · 80 | 15 · 50 | 26 · 10 | Assumed equal to Wafarin |
LAA | 1 · 08 | 0 · 00 | 5 · 00 | [5] |
Relative Risk of Hospitalization, % | ||||
Warfarin vs. aspirin | 1 · 22 | 0 · 64 | 2 · 36 | [20] |
Warfarin vs. clopidogrel plus aspirin | 1 · 22 | 0 · 64 | 2 · 36 | Assumed equal to Aspirin |
Death | ||||
Death from vascular cause, % | ||||
Aspirin alone | 4 · 70 | 4 · 48 | 4 · 92 | [2] |
Clopidogrel plus aspirin | 4 · 70 | 4 · 18 | 5 · 26 | [2] |
Warfarin | 2 · 10 | 1 · 71 | 2 · 69 | |
Dabigatran, 110 mg | 2 · 43 | 2 · 23 | 2 · 63 | [3] |
Dabigatran, 150 mg | 2 · 28 | 2 · 03 | 2 · 53 | [3] |
Apixaban | 1 · 80 | 1 · 54 | 2 · 10 | [13] |
All-cause mortality, % | ||||
Aspirin alone | 6 · 60 | 5 · 53 | 7 · 67 | [2] |
Clopidogrel plus aspirin | 6 · 40 | 5 · 87 | 7 · 13 | [2] |
Warfarin | 2 · 89 | 0 · 50 | 4 · 13 | [3] |
Dabigatran, 110 mg | 3 · 75 | 3 · 51 | 3 · 99 | [3] |
Dabigatran, 150 mg | 3 · 64 | 3 · 28 | 4 · 00 | [3] |
Apixaban | 3 · 52 | 3 · 15 | 3 · 90 | [13] |
Rivaroxaban | 4.50 | 4.01 | 4.99 | [4] |
LAA | 3.20 | 1.56 | 4.84 | [21] |
Ischemic stroke
Hemorrhage
Myocardial infarction
Pericardial effusions
Success rate of LAA occlusion
Hospitalization
Death
Quality of life
Variable | Base-Case | Range | References | |
---|---|---|---|---|
Quality of life | ||||
Mean utility score | ||||
Aspirin alone | 0 · 998 | 0 · 994 | 1 · 0 | [10] |
Clopidogrel plus aspirin | 0 · 998 | 0 · 994 | 1 · 0 | Assumed equal to Aspirin |
Warfarin | 0 · 987 | 0 · 953 | 1 · 0 | [10] |
Dabigatran | 0 · 994 | 0 · 975 | 1 · 0 | |
Apixaban | 0 · 994 | 0 · 975 | 1 · 0 | Assumed equal to Dabigatran |
Rivaroxaban | 0 · 994 | 0 · 975 | 1 · 0 | Assumed equal to Dabigatran |
LAA | 0 · 998 | 0 · 994 | 1 · 0 | Assumed equal to Aspirin |
Stroke | ||||
Mild neurologic sequelae | 0 · 75 | 0 · 75 | 1 · 0 | [10] |
Moderate to severe neurologic | ||||
sequelae | 0 · 39 | 0 · 39 | 1 · 0 | [10] |
Myocardial infarction | 0 · 84 | 0 · 84 | 1 · 0 | [23] |
Hemorrhage | ||||
Minor hemorrhage | 0 · 8 | 0 · 5 | 0 · 99 | |
Major hemorrhage | 0 · 8 | 0 · 5 | 0 · 99 | |
Cost, US$ | ||||
Annual cost of medication or device | ||||
Aspirin alone | 10 · 0 | 5 · 0 | 15 · 0 | [10] |
Clopidogrel plus aspirin | 1,857 · 0 | 365 · 0 | 2,785.5 | [10] |
Warfarin | 180 · 0 | 60 · 0 | 270 · 0 | [10] |
Dabigatran | 3,240 · 0 | 2,500 · 0 | 4,860 | [10] |
Apixaban | 3,920 · 1 | 1960 · 1 | 5,880 · 2 | [25] |
Rivaroxaban | 2,660 · 9 | 1,330 · 4 | 3,991 · 3 | [25] |
LAA | 22,500 | 20,384 | 24,614 | [26], Assumption |
Cost of INR + minimal established patient visit | 26 · 0 | 10 · 0 | 39.0 | [10] |
Short term cost of neurological event | ||||
Moderate to severe ischemic neurological event | 14,680 · 0 | 6,000 · 0 | 25,000 · 0 | [10] |
Minor ischemic neurological event | 9,200 · 0 | 3,500 · 0 | 15,000 · 0 | [10] |
TIA | 7,500 · 0 | 3,000 · 0 | 12,000 · 0 | [10] |
ICH | 38,500 · 0 | 15,000 · 0 | 60,000 · 0 | [10] |
Long term cost of neurological event | ||||
Moderate to severe ischemic neurological event | 5,400 · 0 | 2,000 · 0 | 8,000 · 0 | [10] |
Minor ischemic neurological event | 2,470 · 0 | 1,000 · 0 | 4,000v0 | [10] |
TIA | 5,700 · 0 | 2,000 · 0 | 9,000 · 0 | [10] |
ICH | 7,200 · 0 | 3,000 · 0 | 12,000 · 0 | [10] |
Other costs, US$ | [10] | |||
Transesophageal echocardiogram | 334.0 | 167.0 | 501.0 | [27] |
Major bleeding without residua | 4,400 · 0 | 1,500 · 0 | 6,000 · 0 | [10] |
Minor bleeding | 69 · 0 | 34 · 5 | 200 · 0 | [10] |
Cost of non-stroke, non-hemorrhage death | 10,000 · 0 | 5,000 · 0 | 20,000 · 0 | [10] |
MI | 17,000 · 0 | 5,000 · 0 | 50,000 · 0 | [10] |
Hospitalization for stroke | 80,964 · 0 | 40,482 · 0 | 121,446 · 0 | Assumption |
Hospitalization for pericardial effusions | 73,770 · 0 | 36,885 · 0 | 110,655 · 0 | Assumption |
Cost measurement
Sensitivity analysis
Results
Base-case analysis
Therapy | Total Discounted Costs, USD | Total Discounted QALYs, Year | Cost per QALY | ICER, vs. Aspirin | ICER, vs. Clopidogrel plus Aspirin | ICER, vs. Warfarin | ICER, vs. LAA Occlusion | ICER, vs. Dabigatran 110 mg | ICER, vs. Dabigatran 150 mg | ICER, vs. Rivaroxaban | ICER, vs. Apixaban | ICER, vs. Next-best strategy |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Aspirin | $12,877 | 6 · 12 | $2,104 | --- | Dominateda | Dominateda | Dominateda | Dominateda | Dominateda | Dominateda | Dominateda | --- |
Clopidogrel plus aspirin | $26,287 | 6 · 29 | $4,179 | $78,882 | --- | Dominateda | Dominateda | Dominateda | Dominateda | Dominateda | Dominateda | Extended dominance |
Warfarin | $28,090 | 9 · 45 | $2,972 | $4,568 | $571 | --- | Dominateda | Dominatedb | Dominatedb | Dominateda | Dominatedb | $571 |
LAA Occlusion | $37,789 | 10.99 | $3,438 | $5,115 | $2,447 | $6,298 | --- | Dominatedb | Dominatedb | Dominatedb | Dominatedb | $6,298 |
Dabigatran 110 mg | $42,712 | 8.76 | $4,876 | $11,301 | $6,650 | Dominatedc | Dominatedc | --- | Dominateda | Dominateda | Dominateda | Dominateda |
Dabigatran 150 mg | $43,946 | 9.00 | $4,883 | $10,788 | $6,516 | Dominatedc | Dominatedc | $5,142 | --- | Dominateda | Dominateda | Dominateda |
Rivaroxaban | $51,064 | 9.86 | $5,179 | $10,210 | $6,940 | $56,034 | Dominatedc | $7,593 | $8,277 | --- | Dominateda | Dominateda |
Apixaban | $53,315 | 9.40 | $5,672 | $12,329 | $8,691 | Dominatedc | Dominatedc | $16,567 | $23,423 | Dominatedc | --- | Dominateda |
Sensitivity analysis
Aspirin | Clopidogrel + Aspirin | Warfarin | Dabigatran 110 mg | Dabigatran 150 mg | Apixaban | Rivaroxaban | LAAO | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CHADS2 Score | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY |
0 (0 · 8 %) | $10,117 | 6 · 36 | $24,998 | 6 · 42 | $27,027 | 9 · 54 | $41,569 | 8 · 87 | $43,685 | 9 · 02 | $52,949 | 9 · 44 | $50,966 | 9.98 | $37,567 | 11.01 |
1 (2 · 2 %) | $12,073 | 6 · 19 | $26,627 | 6 · 25 | $30,565 | 9 · 25 | $44,469 | 8 · 60 | $46,627 | 8 · 75 | $55,868 | 9 · 15 | $54,107 | 9.67 | $40,971 | 10.65 |
2 (4 · 5 %) | $15,048 | 5.93 | $29,098 | 5 · 99 | $35,853 | 8 · 81 | $48,807 | 8 · 20 | $51,021 | 8 · 34 | $60,207 | 8 · 71 | $58,766 | 9.19 | $46,033 | 10.11 |
3 (8 · 6 %) | $19,710 | 5 · 52 | $32,949 | 5 · 57 | $43,894 | 8 · 11 | $55,412 | 7 · 57 | $57,698 | 7 · 69 | $66,749 | 8 · 01 | $65,765 | 8.44 | $53,661 | 9.25 |
4 (10 · 9 %) | $22,017 | 5 · 31 | $34,846 | 5 · 36 | $47,753 | 7 · 76 | $58,587 | 7 · 25 | $60,899 | 7 · 37 | $69,859 | 7 · 67 | $69,080 | 8.07 | $57,288 | 8.83 |
5 (12.3 %) | $23,327 | 5.19 | $35,919 | 5.24 | $49,905 | 7.57 | $60,359 | 7.07 | $62,684 | 7.18 | $71,586 | 7.47 | $70,915 | 7.86 | $59,299 | 8.59 |
6 (13.7 %) | $24,571 | 5.08 | $36,937 | 5.13 | $51,922 | 7.38 | $62,021 | 6.90 | $64,357 | 7.01 | $73,198 | 7.28 | $72,626 | 7.66 | $61,177 | 8.36 |
ICER, US$ LAAO vs. each strategy | Score 0: $5,903 | Score 0: $2,738 | Score 0: $7,170 | |||||||||||||
Score 1: $6,479 | Score 1: $3,260 | Score 1: $7,433 | ||||||||||||||
Score 2: $7,413 | Score 2: $4,110 | Score 2: $7,831 | ||||||||||||||
Score 3: $9,102 | Score 3: $5,628 | Score 3: $8,568 | Dominated | Dominated | Dominated | Dominated | --- | |||||||||
Score 4: $10,020 | Score 4: $6,467 | Score 4: $8,911 | ||||||||||||||
Score 5: $10,580 | Score 5: $6,979 | Score 5: $9,210 | ||||||||||||||
Score 6: $11,160 | Score 6: $7,505 | Score 6: $9,444 | ||||||||||||||
HAS-BLED Score | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY |
0 (1.13 %) | $12,877 | 6 · 12 | $26,287 | 6 · 29 | $36,827 | 9 · 40 | $62,062 | 8 · 64 | $61,719 | 8 · 88 | $72,551 | 9 · 30 | $69,642 | 9.78 | $38,858 | 10.98 |
1 (1.08 %) | $12,877 | 6 · 12 | $26,287 | 6 · 29 | $34,333 | 9 · 42 | $59,791 | 8 · 66 | $59,450 | 8 · 89 | $69,999 | 9 · 31 | $66,679 | 9.79 | $38,552 | 10.99 |
2 (1.88 %) | $12,877 | 6 · 12 | $26,287 | 6 · 29 | $53,095 | 9 · 31 | $76,902 | 8 · 55 | $76,534 | 8 · 77 | $89,207 | 9 · 21 | $88,969 | 9.69 | $40,851 | 10.97 |
3 (3.74 %) | $12,877 | 6 · 12 | $26,287 | 6 · 29 | $88,462 | 9 · 09 | $109,305 | 8 · 35 | $108,814 | 8 · 55 | $125,481 | 9 · 02 | $130,998 | 9.50 | $45,208 | 10.95 |
4 (8.7 %) | $12,877 | 6 · 12 | $26,287 | 6.29 | $156,713 | 8 · 67 | $172,530 | 7 · 94 | $171,469 | 8 · 09 | $195,786 | 8 · 65 | $212,146 | 9.13 | $53,713 | 10.89 |
5 (12.5 %) | $12,877 | 6 · 12 | $26,287 | 6.29 | $191,794 | 8 · 45 | $205,517 | 7 · 73 | $203,929 | 7 · 85 | $232,133 | 8 · 45 | $253,872 | 8.94 | $58,139 | 10.87 |
ICER, US$ LAAO vs. each strategy | Score 0: $5,346 | Score 0: $2,680 | Score 0: $1,285 | |||||||||||||
Score 1: $5,272 | Score 1: $2,610 | Score 1: $2,687 | ||||||||||||||
Score 2: $5,768 | Score 2: $3,112 | Score 2: Dominated | ||||||||||||||
Score 3: $6,694 | Score 3: $4,060 | Score 3: Dominated | Dominated | Dominated | Dominated | Dominated | --- | |||||||||
Score 4: $8,561 | Score 4: $5,962 | Score 4: Dominated | ||||||||||||||
Score 5: $9,529 | Score 5: $6,955 | Score 5: Dominated | ||||||||||||||
Time horizon | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY |
5 years | $6,100 | 3 · 47 | $12,529 | 3 · 50 | $6,898 | 4 · 02 | $17,516 | 3 · 94 | $17,374 | 3 · 97 | $20,356 | 4 · 03 | $17,040 | 4.08 | $24,015 | 4.25 |
10 years | $9,788 | 5 · 06 | $19,929 | 5 · 15 | $14,876 | 6 · 63 | $29,508 | 6 · 36 | $29,707 | 6 · 46 | $35,233 | 6 · 63 | $31,205 | 6.81 | $29,026 | 7.28 |
15 years | $11,801 | 5 · 78 | $24,048 | 5 · 92 | $22,111 | 8 · 34 | $37,471 | 7 · 85 | $38,190 | 8 · 02 | $45,834 | 8 · 31 | $42,397 | 8.63 | $33,699 | 9.44 |
ICER, US$ LAAO vs. each strategy | 0 5 years: $22,968 | 0 5 years: $15,315 | 5 years: $74,422 | 5 years: $20,965 | 05 years: $23,718 | 5 years: $16,632 | 5 years: $41,029 | |||||||||
10 years: $8,666 | 10 years: $4,217 | 10 years: $21,769 | 10 years: Dominated | 10 years: Dominated | 10 years: Dominated | 10 years: Dominated | --- | |||||||||
15 years: $5,983 | 15 years: $2,742 | 15 years: $10,535 | 15 years: Dominated | 15 years: Dominated | 15 years: Dominated | 15 years: Dominated | ||||||||||
LAAO costs | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY | Cost | QALY |
Low cost ($20,384) | $12,877 | 6.12 | $26,287 | 6.29 | $28,090 | 9.45 | $42,712 | 8.76 | $43,946 | 9.00 | $53,315 | 9.40 | $51,064 | 9.86 | $36,731 | 10.99 |
Base-case ($22,500) | $12,877 | 6.12 | $26,287 | 6.29 | $28,090 | 9.45 | $42,712 | 8.76 | $43,946 | 9.00 | $53,315 | 9.40 | $51,064 | 9.86 | $37,789 | 10.99 |
High cost ($24,614) | $12,877 | 6.12 | $26,287 | 6.29 | $28,090 | 9.45 | $42,712 | 8.76 | $43,946 | 9.00 | $53,315 | 9.40 | $51,064 | 9.86 | $38,846 | 10.99 |
ICER, US$ LAAO vs. each strategy | Low cost: $4,898 | Low cost: $2,222 | Low cost: $5,611 | |||||||||||||
Base-case: $5,115 | Base-case: $2,447 | Base-case: $6,298 | Dominated | Dominated | Dominated | Dominated | --- | |||||||||
High cost: $5,332 | High cost: $2,672 | High cost: $6,984 |