Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
APPENDIX
The cost-effectiveness of radiofrequency catheter ablation as firstline treatment for paroxysmal atrial fibrillation: results from a
MANTRA-PAF substudy
Brief title: Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
Mattias Aronsson, Håkan Walfridsson, Magnus Janzon, Ulla Walfridsson, Jens Cosedis Nielsen, Peter
Steen Hansen, Arne Johannessen, Pekka Raatikainen, Gerhard Hindricks, Ole Kongstad, Steen
Pehrson, Anders Englund, Juha Hartikainen, Leif Spange Mortensen, Lars-Åke Levin.
1. Information about appendix
Most relevant model assumptions are presented in section 2.
Assumptions about reversion rate, crossover rate and CHADS2-score are described in section 3 and 4.
Supplementary data about model parameters are presented in section 5. Standard deviations presented
in the table were used for probabilistic sensitivity analyses. The range of parameter values presented
in the table was used when alternative scenarios were tested deterministically. All costs and prices are
in Swedish krona (SEK). 8.7 SEK ≈ 1 Euro.
A procedural model is presented in section 6.
The importance of the time horizon is shown in section 7.
2. Assumptions
 The clinical benefit of catheter ablation is mainly driven by a reduced risk of ischemic stroke
and events related to the use of oral anti-coagulation treatment.
 Patients not successfully treated with AAD will over time do crossovers to catheter ablation
(see section 3).
 Crossover patients (from AAD to RFA) are expected to hold the same risk of events as
patients randomized to RFA.
 Patients with known AF are expected to be treated with warfarin.
 Additional ablations were allowed in 50 % of the patients with AF recurrence >24 months
after first ablations procedure.
All assumptions were rigorously tested in sensitivity analyses.
3. Reversion and crossover
The recurrence of AF during the first 24 months was obtained from the MANTRA-PAF trial for both
the AAD- and RFA-treated patients.
The crossover rate for first 24 months was obtained from MANTRA-PAF study data.
1
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
Recurrence of AF after first 24 months in patients treated with AAD was obtained from Pappone et al
(1). A non-linear model was used as the reversion rate to AF declined with time.
The long-term effectiveness of RFA is currently not well established due to a continuous development
of the RFA-technique. The effectiveness of RFA may be better than in the MANTRA-PAF study and
the other studies used for the reversion rate calculation (2-6). The parameter was rigorously tested in
sensitivity analyses.
No relevant data regarding crossover rate in patients treated with RFA were identified during the
literature search. We made the assumption that patients with PAF not successfully treated with AAD
will do crossovers to RFA, as second-line RFA are recommended in guidelines and been proven both
clinical efficient and cost-effective. Three scenarios with different readiness of offering RFA to AADpatients with PAF are shown in the manuscript.
4. CHADS2-Score
CHADS2-score were used to predict the stroke risk because CHA2DS2-VASc were not widely used
when the MANTRA-PAF study were initiated. The hypothetic population in the model was expected
to have the same distribution between the CHADS2 states as the MANTRA-PAF study population (7).
The CHADS2 –score increased thru the model as patients become older than 75 year and experienced
strokes.
2
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
5. Supplementary tables with important parameters
Determ
inistic
Standar
d error
Sensitivity
test range
Distribution
Alfa
Beta
Reference/Comment
Monthly drug cost
Beta blockers
31
(15 – 60)
Deterministic
ACE-inhibitors
156
(50 – 300)
Deterministic
Monthly warfarin cost
>24 months
Drugs and monitoring visits
517
(250 – 750)
Deterministic
(8)
Discounting
Discount costs
3%
(0 – 10)
Deterministic
Guidelines from Swedish authority TLV.
Discount effects
3%
(0 – 10)
Deterministic
Guidelines from Swedish authority TLV.
QALY-decreases
QALY-loss from Ischemic
stroke (yearly)
QALY-loss from
Hemorrhagic stroke
(yearly)
QALY-loss from MI (first
year)
QALY-loss from
symptomatic AF
QALY-loss from RFAprocedure
www.FASS.se/, Unpublished MANTRAPAF-data
www.FASS.se/, Unpublished MANTRAPAF-data
0.15
0.012
(0 – 0.3)
Beta
132.3
750
(9) Expected to include the effects disability
0.3
0.041
(0 – 0.45)
Beta
36.8
85.87
(9) Expected to include the effects disability
(0 – 0.3)
0.19
(10)
0.13
0.025
(0 – 0.2)
Normal
Unpublished MANTRA-PAF-data
0
0
(0 – 0)
Normal
Only for sensitivity analyses
QALY overall population
3
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
40–49
0.863
0.009
Normal
50–59
0.839
0.010
Normal
60–69
0.808
0.011
Normal
70–79
0.794
0.015
Normal
80–88
0.733
0.028
Normal
Operation-modeltransitions
Procedure mortality
Tamponade
Stroke
Stenosis
Hemothorax
Femoral pseudo aneurysm
Transient ischemic attack
Artero venous fistulae
0.046 %
1.22 %
0.28 %
0.74 %
0.16 %
0.54 %
0. 66 %
0.42 %
Relative risk
Relative risk NSR
0.625
0.3036
ADR
Fatal ADR per year (year
>2)
0.32%
0.05%
Crossover and reversion
rate per months
Crossover rate
>24 months
Reversion rate AAD
1.1 %
1.9 %
Beta
Beta
Beta
Beta
Beta
Beta
Beta
Beta
0.3
(11) Used for adjusting MANTRA-PAF
data for age in the model
(11) Used for adjusting MANTRA-PAF
data for age in the model
(11) Used for adjusting MANTRA-PAF
data for age in the model
(11) Used for adjusting MANTRA-PAF
data for age in the model
(11) Used for adjusting MANTRA-PAF
data for age in the model
4
107
20
53
14
47
47
37
8741
8638
7134
7101
8731
8698
7107
8708
(12) Used >24 months
(12) Used >24 months
(12) Used >24 months
(12) Used >24 months
(12) Used >24 months
(12) Used >24 months
(12) Used >24 months
(12) Used >24 months
Lognormal
(13)
(0 – 0.5)
Beta
Meta-analysis in (14). Standard deviation
used in the probabilistic sensitivity analyses
was estimated.
(0 – 2)
Beta
Calculated from the reversion
(0 – 4)
Beta
Calculation based on (15). Standard
4
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
>24 months
Reversion rate RFA
>24 months
deviation estimated.
Meta-analysis of (2-6)
(0 – 2)
Beta
0.178
(0.1 – 0.5)
Beta
3319
18 601
(16)
0.269
(0.1 – 0.5)
Beta
4716
12 796
(16)
0.367
(0.1 – 0.5)
Beta
7810
21 298
(16)
Intervention/ investigation
cost
MR
9968
(5000 – 15 000)
Deterministic
Percutaneous intervention
17542
(10 000 – 30 000)
Deterministic
Symptomatic AF
Proportion symptomatic
55 %
(30 – 80)
Deterministic
Unpublished MANTRA-PAF-data
(15 000 – 45 000)
(0 -700)
Deterministic+
Range
Deterministic
Deterministic+
Range
Deterministic
(17) Range 10 000 – 40 000 tested in
sensitivity analyses
(18)
(17) Range 0 – 1500 tested in sensitivity
analyses
(10) Standard deviation estimated.
Normal
(19)
Risk of Death Stroke
Risk of death, acute.
CHADS= 0-1
Risk of death, acute.
CHADS= 2
Risk of death, acute.
CHADS= 3-4
0.8 %
0.1
Cost for the Department of Cardiology,
Linköping University Hospital
Cost for the Department of Cardiology,
Linköping University Hospital
AF
Cost events
Cost severe bleeding
26 339
Cost GI-bleeding
Cost minor bleeding
31 377
350
Cost MI
184 115
10 000
Stroke cost
Hospitalization stroke
84 999
1 088
(50 000 – 300 000)
5
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
(acute)
Social service (Year 1)
Health care (Year 1)
Primary care (Year >1)
Social service (Year >1)
50 746
36 760
22 400
40 856
81
Normal
(19)
(19)
(19)
(19)
Procedure consumption and cost
Mean SD
Cost
ECG before
1
231
ECG after
1
231
Physicians** minutes
279
Range
Reference
50 000 – 150 000
Cost for the Department of Cardiology, Linköping
University Hospital
Cost for the Department of Cardiology, Linköping
University Hospital
Unpublished MANTRA-PAF-data/ Cost for the
Department of Cardiology, Linköping University
Hospital
Unpublished MANTRA-PAF-data/ Cost for the
Department of Cardiology, Linköping University
Hospital
Unpublished MANTRA-PAF-data/ Cost for the
Department of Cardiology, Linköping University
Hospital
Unpublished MANTRA-PAF-data/ Cost for the
Department of Cardiology, Linköping University
Hospital
Unpublished MANTRA-PAF-data/ Unit cost from
Linkoping University hospital
Cost for the Department of Cardiology, Linköping
University Hospital
Cost southeast health care region of Sweden
Cost southeast health care region of Sweden
127.30 5588
Anesthetist (phy) minutes 5.65
9.68
134
Anesthetist (nur) minutes
148
108.92 1778
Other ass per minutes
446
202.02 4459
Hospital care
2.28
1.43
Ablation materials
1
43 314
Other costs
Total cost
1
24050
90294
10 185
6
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
Monthly risk of events in AF-patients
Warfarin
Ischemic stroke
Low risk CHADS: 0-1
Moderate risk CHADS: 2
High risk: CHADS: 3-6
0.053%
0.094%
0.158%
Bleeding stroke
Low risk CHADS: 0-1
Moderate risk CHADS: 2
High risk: CHADS: 3-6
0.07%
0.07%
0.07%
Other events
Severe bleeding
GI-bleeding
Minor bleeding
Myocardial infarction
0.13%
0.09%
1.48%
0.04%
7
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
Life tables Swedish population 2011
Age
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
Monthly mortality
0,007%
0,008%
0,009%
0,011%
0,012%
0,012%
0,014%
0,013%
0,016%
0,020%
0,022%
0,026%
0,024%
0,031%
0,031%
0,033%
0,036%
0,043%
0,048%
0,048%
0,057%
0,059%
0,069%
0,075%
0,089%
0,092%
0,102%
0,106%
0,129%
0,139%
0,147%
0,162%
0,185%
0,197%
0,240%
0,257%
0,274%
0,328%
0,368%
0,403%
0,467%
0,564%
0,605%
0,689%
0,771%
0,877%
1,015%
1,148%
1,302%
1,450%
1,616%
8
1,850%
2,022%
2,204%
2,398%
2,605%
2,824%
3,056%
3,302%
3,563%
3,840%
4,134%
4,449%
4,784%
5,144%
5,531%
5,950%
6,403%
6,896%
7,434%
8,022%
8,667%
9,377%
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
Baseline patients (≤50 year)
Baseline
N
Age (mean)
Age (median)
Female (%)
Systolic BP
Diastolic BP
Height
Weight
NYHA class 1
CCS class 1
Underlying disease
Floppy mitral valve
Coronary artery disease
AP
Prior MI
Prior PCI
Prior CABG
CAG with > 50% stenosis
Other structural disease
Valvular heart disease
History of valve intervention.
Left ventricular. hypertrophy
Congenital heart disease
Hypertension
Previous rate control
Beta blocker
Calcium antagonist
Digoxin
His-ablation
Previous rhythm control
Beta blocker
RA isthmus block
Other RA ablation
Pacemaker with PES
Previous SVT
Atrial tachycardia
Other SVT
AVNRT
WPW
Focal atrial tachycardia
Atrial fibrillation (R)
Atrial flutter
Ischemic stroke
RFA
AAD
33
43
42.85
45
21
132.63
79.50
179.81
90.88
1.00
1.00
0.30
0.00
0.03
0.00
0.03
0.03
0.00
0.00
0.12
0.00
0.00
0.03
0.00
0.15
0.55
0.42
0.12
0.09
0.00
0.64
0.64
0.03
0.00
0.00
0.03
0.03
0.00
0.00
0.00
0.00
0.03
0.03
0.00
42.14
43.5
12
130.27
79.98
181.58
85.53
0.98
1.00
0.19
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.02
0.00
0.00
0.02
0.00
0.19
0.42
0.35
0.07
0.07
0.00
0.51
0.51
0.02
0.00
0.00
0.05
0.02
0.00
0.02
0.02
0.00
0.00
0.05
0.00
9
p-value
0.63
0.262
0.523
0.82
0.341
0.09
0.385*
0.24
0.256
0.256
0.256
0.09
0.852
0.697
0.278
0.509
0.449
0.739
0.283
0.283
0.852
0.723
0.667
0.385
0.385
0.256
0.723
-
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
Transient ischemic attack
Systemic peripheral embolism
Intracranial hemorrhage
Sinus bradycardia/SSD
Sinoatrial exit block
Tachycardia-bradycardia
AV-block
Most advanced degree
Pacemaker insertion
ICD insertion
Diabetes mellitus
Chronic lung disease
Thyroid disease
0.00
0.00
0.00
0.03
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.06
0.09
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.07
0.00
0.00
0.256
0.24
0.105
0.044
* Mann-Whitney U- Test, All other: independent sample t-test
Baseline patients >50 year
Baseline
N
Age (mean)
Age (median)
Female
Systolic BP
Diastolic BP
Height
Weight
NYHA class 1
CCS class 1
Coronary artery disease
AP
Prior MI
Prior PCI
Prior CABG
CAG with > 50% stenosis
Other structural disease
Valvular heart disease
History of valve intervention.
Left ventricular. hypertrophy
Congenital heart disease
Hypertension
Previous rate control
Beta blocker
Calcium antagonist
Digoxin
His-ablation
Previous rhythm control
RFA
AAD
p-value
108
60.29
60
0.34
139.34
82.16
177.66
84.58
0.86
0.96
103
59.79
59
0.36
136.75
82.03
175.96
83.96
0.83
0.96
0.80
0.33
0.93
0.19
0.76
0.41*
0.94*
0.05
0.01
0.01
0.00
0.03
0.01
0.11
0.06
0.01
0.07
0.00
0.34
0.74
0.61
0.12
0.16
0.00
0.07
0.02
0.00
0.02
0.01
0.00
0.01
0.11
0.15
0.01
0.12
0.02
0.44
0.65
0.57
0.07
0.12
0.00
0.07
0.18
0.07
0.12
0.07
0.12
0.10
0.31
0.30
0.10
0.29
0.10
0.49
0.46
0.49
0.29
0.35
0.26
10
0.47
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
Beta blocker
RA isthmus block
Other RA ablation
Pacemaker with PES
Previous cardioversion
Previous SVT
Atrial tachycardia
Other SVT
AVNRT
WPW
Focal atrial tachycardia
Atrial fibrillation (R)
Atrial flutter
Ischemic stroke
Transient ischemic attack
Systemic peripheral embolism
Intracranial hemorrhage
Sinus bradycardia/SSD
Sinoatrial exit block
Tachycardia-bradycardia
AV-block
Most advanced degree
Pacemaker insertion
ICD insertion
Diabetes mellitus
Chronic lung disease
Thyroid disease
0.45
0.45
0.03
0.00
0.00
0.06
0.02
0.00
0.01
0.04
0.00
0.01
0.02
0.00
0.04
0.02
0.04
0.02
0.01
0.09
0.06
0.05
0.03
0.06
0.01
0.06
0.06
0.44
0.44
0.00
0.00
0.00
0.02
0.01
0.00
0
0.01
0.00
0
0
0.00
0.01
0.04
0.01
0.00
0.00
0.08
0.06
0.03
0.02
0.05
0.03
0.09
0.06
0.50
0.50
0.12
0.20
0.12
0.07
0.15
0.07
0.10
0.15
0.17
0.15
0.10
0.07
0.28
0.23
0.19
0.15
0.23
0.14
0.31
0.23
* Mann-Whitney U- Test, All other: independent sample t-test
6. Structure procedural model
Every RFA-intervention could be repeated up to three times and complication could occur after every
procedure. Complications include risk for local hematomas, pseudoaneurysm, vasovagal reaction,
infection, chest pain or discomfort, arrhythmias, pericardial effusion, transient ischemic attack,
cerebrovascular accident, cardiac tamponade, pericarditis and death.
7. Time horizon
11
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
As shown below, the result is dependent of the time horizon in the model. The effect of an
additional year on the ICER declined after approximately 20 years.
8. Sensitivity analyses of the overall population
Parameter
Value
Cost RFA-procedure
Cost RFA-procedure
RFA proc. mortality
QALY weight (both groups)
QALY decrement isch.stroke
QALY decrement isch.stroke
RR NSR
RR NSR
€/QALY
€5 000
€15 000
0.5%
0.8
0.1
0.2
0.75
0.5
9. PROBABILISTIC SENITIVITY ANALYSES
12
20 146
76 716
66 924
59 559
50 070
51 080
53 457
47 903
Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
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Appendix- Cost-effectiveness of radiofrequency catheter ablation as first-line treatment
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