Skip to main content
Erschienen in: BMC Cardiovascular Disorders 1/2016

Open Access 01.12.2016 | Research article

Cost-effectiveness analysis of left atrial appendage occlusion compared with pharmacological strategies for stroke prevention in atrial fibrillation

verfasst von: Vivian Wing-Yan Lee, Ronald Bing-Ching Tsai, Ines Hang-Iao Chow, Bryan Ping-Yen Yan, Mehmet Gungor Kaya, Jai-Wun Park, Yat-Yin Lam

Erschienen in: BMC Cardiovascular Disorders | Ausgabe 1/2016

Abstract

Background

Transcatheter left atrial appendage occlusion (LAAO) is a promising therapy for stroke prophylaxis in non-valvular atrial fibrillation (NVAF) but its cost-effectiveness remains understudied. This study evaluated the cost-effectiveness of LAAO for stroke prophylaxis in NVAF.

Methods

A Markov decision analytic model was used to compare the cost-effectiveness of LAAO with 7 pharmacological strategies: aspirin alone, clopidogrel plus aspirin, warfarin, dabigatran 110 mg, dabigatran 150 mg, apixaban, and rivaroxaban. Outcome measures included quality-adjusted life years (QALYs), lifetime costs and incremental cost-effectiveness ratios (ICERs). Base-case data were derived from ACTIVE, RE-LY, ARISTOTLE, ROCKET-AF, PROTECT-AF and PREVAIL trials. One-way sensitivity analysis varied by CHADS2 score, HAS-BLED score, time horizons, and LAAO costs; and probabilistic sensitivity analysis using 10,000 Monte Carlo simulations was conducted to assess parameter uncertainty.

Results

LAAO was considered cost-effective compared with aspirin, clopidogrel plus aspirin, and warfarin, with ICER of US$5,115, $2,447, and $6,298 per QALY gained, respectively. LAAO was dominant (i.e. less costly but more effective) compared to other strategies. Sensitivity analysis demonstrated favorable ICERs of LAAO against other strategies in varied CHADS2 score, HAS-BLED score, time horizons (5 to 15 years) and LAAO costs. LAAO was cost-effective in 86.24 % of 10,000 simulations using a threshold of US$50,000/QALY.

Conclusions

Transcatheter LAAO is cost-effective for prevention of stroke in NVAF compared with 7 pharmacological strategies.

Condensed abstract

The transcatheter left atrial appendage occlusion (LAAO) is considered cost-effective against the standard 7 oral pharmacological strategies including acetylsalicylic acid (ASA) alone, clopidogrel plus ASA, warfarin, dabigatran 110 mg, dabigatran 150 mg, apixaban, and rivaroxaban for stroke prophylaxis in non-valvular atrial fibrillation management.
Abkürzungen
AF
Atrial fibrillation
ASA
Acetylsalicyclic acid
ICERs
Incremental cost-effectiveness ratios
ICH
Intracranial hemorrhage
LAA
Left atrial appendage
LAAO
Left atrial appendage occlusion
NOACs
Novel oral anticoagulants
NVAF
Non-valvular atrial fibrillation
QALYs
Quality-adjusted life years
TEE
Transesophageal echocardiography
TIA
Transient ischemic attack

Background

Atrial fibrillation (AF) is associated with 4–5 fold increase risk for thromboembolic stroke [1]. Oral anticoagulation therapy with warfarin is the standard therapy for stroke prevention, but is difficult to maintain within the narrow therapeutic range and is under-prescribed in clinical practice. Potential alternatives to warfarin include anti-platelet therapy [2], novel oral anticoagulants (NOACs) such as direct thrombin or factor Xa inhibitors [3, 4] and exclusion of the left atrial appendage (LAA) as a major embolic source [5, 6]. The randomized-controlled WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation (PROTECT-AF) trial [5] demonstrated that device occlusion of the LAA orifice by the WATCHMAN device (Boston Scientific, Natick, MA, USA) was non-inferior to warfarin for the prevention of thromboembolic events in NVAF patients. The cost of this device ranges from US$5,770 to US$10,000 depending on the country.
According to recent published economic evaluation studies of LAA compared with warfarin or NOACs, the results indicated that LAA was a cost-effective alternative for stroke prevention in AF patients [7, 8]. However, comprehensive comparison with LAA and each oral anticoagulant should be evaluated to demonstrate significant outcomes. This study estimated the lifetime cost-effectiveness of transcatheter left atrial appendage occlusion (LAAO) for stroke prophylaxis in a hypothetical cohort of 65-year-old patients with non-valvular AF as compared to other pharmacological strategies.

Methods

Decision analytical model

A Markov decision analytic model was used to perform a cost-effectiveness analysis from a US healthcare provider perspective expressed in US dollars. The model was developed using TreeAge Pro Suite 2014 software (TreeAge Software, Inc., Williamstown, MA) for evaluating the long-term costs and effectiveness of treatment strategies for stroke prevention. Outcome measures included quality-adjusted life years (QALYs), lifetime costs and incremental cost-effectiveness ratios (ICERs). All costs and QALYs were discounted at an annual rate of 3 %. The ICERs of < US$50,000 per QALY was considered cost-effective [9].

Model

The model of patients wth AF for stroke prevention was adapted from literature and cardiology consultation [8, 10]. A cohort of 65-year-old patients with non-valvular AF without contraindication to anti-thrombotic therapies was simulated moving between different health states in each Markov cycle of 1 year. The time horizon was lifetime (85 years old). Health states in the model included patient in AF without event, with event before, ischemic stroke (no residual, mild moderate to severe, fatal), transient ischemic attack (TIA), hemorrhage [minor, major, intracranial hemorrhage (ICH), fatal], myocardial infarction (MI), death from vascular cause, and death from all causes. Seven different pharmacological strategies for stroke prevention including acetylsalicyclic acid (ASA) alone (75 to 100 mg), clopidogrel (75 mg) plus ASA, warfarin, dabigatran 110 mg, dabigatran 150 mg, apixaban (5 mg) and rivaroxaban (20 mg) were compared with LAAO. After LAAO, we assumed patients were treated with warfarin for 45 days followed by clopidogrel plus ASA for 180 days, and then lifelong ASA in our study model as in the WATCHMAN trial. There are studies such as the ASA Plavix Feasibility Study with Watchman Left Atrial Appendage Closure Technology (ASAP) study, which used antiplatelet therapy alone after LAAO [5, 11, 12].

Model parameters

Base-case values for analytic model were derived from published randomized studies including Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE), Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY), Apixaban for Reduction in Stroke and Other Throm-boembolic Events in Atrial Fibrillation (ARISTOTLE), Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF), Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation (PROTECT-AF), and Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device In Patients with Atrial Fibrillation Versus Long Term Warfarin Therapy (PREVAIL) trials [25, 13, 14]. Table 1 summarized the clinical inputs and data sources used in the base-case analysis. Warfarin event rates were pooled warfarin events from RE-LY, ROCKET-AF, and ARISTOTLE trails [3, 4, 13].
Table 1
Clinical inputs for base-case value and ranges in decision analytic model
Variable
Base-Case
Range
References
Stroke
 Annual rate of ischemic stroke, %
  Aspirin alone
2 · 80
2 · 80
4 · 50
[2, 18]
  Clopidogrel plus aspirin
1 · 90
1 · 69
2 · 11
[2]
  Warfarin
1 · 21
1 · 05
1 · 42
[3, 4, 13]
  Dabigatran, 110 mg
1 · 34
1 · 31
1 · 55
[3, 15]
  Dabigatran, 150 mg
0 · 92
0 · 75
1 · 09
[3, 15]
  Apixaban
0 · 97
0 · 78
1 · 19
[13, 16]
  Rivaroxaban
1 · 34
1 · 07
1 · 66
[4, 16]
  LAA
0 · 84
0 · 40
1 · 10
[5, 14]
 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
[15, 17]
  Moderate to severe neurologic sequelae
40 · 20
35 · 30
45 · 10
[15, 17]
  Mild neurologic sequelae
42 · 50
37 · 60
47 · 40
[15, 17]
  No residual neurologic sequelae
9 · 10
6 · 20
12 · 00
[15, 17]
  Annual rate of TIA, %
28 · 00
25 · 00
33 · 00
[15, 17]
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
[3, 4, 13]
  Dabigatran, 110 mg
13 · 20
12 · 60
13 · 80
[3, 19]
  Dabigatran, 150 mg
14 · 80
14 · 20
15 · 50
[3, 19]
  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
[3, 4, 13]
  Dabigatran, 110 mg
2 · 87
2 · 50
3 · 32
[3, 19]
  Dabigatran, 150 mg
3 · 32
2 · 89
3 · 82
[3, 19]
  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
[3, 4, 13]
  Dabigatran, 110 mg
0 · 23
0 · 14
0 · 32
[3, 15]
  Dabigatran, 150 mg
0 · 30
0 · 20
0 · 40
[3, 15]
  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
[3, 4, 13]
  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
[3, 4, 13]
  Dabigatran, 110 mg
0 · 82
0 · 61
1 · 12
[3, 19]
  Dabigatran, 150 mg
0 · 81
0 · 60
1 · 09
[3, 19]
  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
[5, 14]
 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
[3, 4, 13]
  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

The annual ischemic stroke rates were 2 · 8 %, 1 · 9 %, 1 · 21 %, 1 · 34 %, 0 · 92 %, 0 · 97 %, 1 · 34 % and 0 · 84 % for ASA alone, clopidogrel plus ASA, warfarin, dabigatran 110 mg, dabigatran 150 mg, apixaban, rivaroxaban, and LAA occlusion, respectively [24, 13, 1518]. Additionally, TIA accounted for 28 % [15, 17] of all neurological ischemic events in this model. The annual ischemic stroke rate of LAA occlusion was pooled by PROTECT-AF and PREVAIL trails [5, 14]. Proportion of 4 sub-classifications of ischemic stroke (no residual, mild, moderate to severe, fatal) varied according to therapy [15, 17].

Hemorrhage

Hemorrhages were classified into 4 categories: minor, major, ICH and fatal (Table 1). The annual rates of ICH were 0 · 2 %, 0 · 4 %, 0 · 75 %, 0 · 23 %, 0 · 3 %, 0 · 33 %, and 0 · 5 % for ASA alone, clopidogrel plus ASA, warfarin, dabigatran 110 mg, dabigatran 150 mg, apixaban, and rivaroxaban, respectively [24, 13, 15]. The rate of ICH after LAAO was 0 · 37 % for the first year and 0 · 2 % for the second year onwards. A pro-rata method was used to estimate the event rates for LAAO based on patients’ duration of taking ASA, clopidogrel plus ASA, or warfarin therapy (Table 1). We assumed the bleeding rate in the first year after LAAO was lower than warfarin or clopidogrel plus ASA since patients were treated with warfarin for only 45 days followed by clopidogrel plus ASA for 180 days. Bleeding rate from the second year onwards was assumed to be the same as ASA alone [5, 12].

Myocardial infarction

The annual rates of MI was 0 · 9 % for ASA, 0 · 7 % for clopidogrel plus ASA, 0 · 78 % for warfarin, 0 · 82 % for dabigatran 110 mg, 0 · 81 % for dabigatran 150 mg, 0 · 53 % for apixaban, and 0 · 91 % for rivaroxaban [24, 13, 19]. We assumed the rate of MI in the first year after LAAO was lower than warfarin or clopidogrel plus ASA since patients were treated with warfarin for only 45 days followed by clopidogrel plus ASA for 180 days. The rate of MI from the second year onwards was assumed to be the same as ASA alone [5, 12].

Pericardial effusions

The rate of serious pericardial effusions was 2 · 07 % for patients who received LAAO within 7 days based on the PROTECT-AF and PREVAIL studies [5, 14].

Success rate of LAA occlusion

LAAO success was defined when anticoagulation could be discontinued after implantation of LAAO device. According to published data, the success rate of LAAO was 86.8 % and others were under warfarin therapy in the LAAO strategy [18].

Hospitalization

The rates of hospitalization may be occurred after patients with moderate to severe stroke or pericardial effusions which were obtained from the RE-LY [3], PROTECT-AF [5], and the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) trial [20]. The hospitalization rates for warfarin, dabigatran 110 mg, dabigatran 150 mg, and LAAO device were 20 · 8 %, 20 · 2 %, 19 · 4 %, and 1 · 08 %, respectively. The rates of apixaban and rivaroxaban were assumed to be the same as warfarin (Table 1).

Death

The rates of cardiovascular and all-cause mortality for ASA alone, clopidogrel plus ASA, warfarin, dabigatran 110 mg, dabigatran 150 mg and apixaban were 4 · 7 % and 6 · 6 %, 4 · 7 % and 6 · 4 %, 2 · 1 % and 2 · 89 %, 2 · 43 % and 3 · 75 %, 2 · 28 % and 3 · 64 %, 1 · 8 % and 3 · 52 %, respectively [24, 13]. The all-cause mortality rates of rivaroxaban and LAAO were 4.5 % and 3.2 % input the model [4, 21].

Quality of life

Health utilities were obtained from published data (Table 2). The mean utility score was 0 · 998 for ASA, 0 · 987 for warfarin [10]. The utility score for dabigatran of 0 · 994 was based on estimation of previous studies for another direct thrombin inhibitor, ximelagatran [15, 17, 22]. The utility score for dual anti-platelet therapy with clopidogrel plus ASA, and LAAO were assumed to be the same as ASA; otherwise, the utility score for apixaban and rivaroxaban were assumed to be the same as dabigatran in this study.
Table 2
Health utilities and costs for base-case value and ranges in decision analytic model
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
[17, 19]
  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
[1517, 24]
  Major hemorrhage
0 · 8
0 · 5
0 · 99
[1517, 24]
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
The mean utility score was 0 · 75 for mild stroke, 0 · 39 for moderate to severe stroke [10]. The utility score of MI (0 · 84) was derived from a nationally representative EQ-5D index scores for a study of chronic conditions in the US [23]. The utility score for minor or major hemorrhage was 0.8 [1517, 24].

Cost measurement

Direct inpatient and outpatient medical costs were estimated from a healthcare provider perspective (Table 2). The cost data for the base-case and their ranges were based on a two cost-effectiveness studies of stroke prevention in AF patients [10, 25]. These costs included the costs of anti-thrombotic therapy, hemorrhage, neurological ischemia, dyspepsia, or MI. The estimated cost for LAAO procedure was based on the mean charge of US$14,614 for LAA implantation procedure [26] plus the cost of the LAA occluding device of US$7,885 (US$5,770-US$10,000) that led to the total cost in our analysis as US$22,500. Transesophageal echocardiography (TEE) was performed at the time of LAA device implantation and at 45 days, thus the cost of TEE was US$334 [27].

Sensitivity analysis

One-way sensitivity analysis was performed by varying CHADS2 score, HAS-BLED score, time horizons, and different costs of LAA occlusion for all treatment strategies in this study. The stroke rate for patients with AF was increased by CHADS2 score (0–6), which were assumed to be 0 · 8 %, 2 · 2 %, 4 · 5 %, 8 · 6 %, 10 · 9 %, 12.3 % and 13.7 %, respectively [18]. The hemorrhage rates were increased by HAS-BLED score (0–5 score), which were assumed to be 1 · 13 %, 1 · 02 %, 1 · 88 %, 3 · 74 %, 8 · 7 %, and 12 · 5 %, respectively [8]. Time horizon was varied from 20 to 5, 10, and 15 years to assess shorter-term cost-effectiveness from a start-age of 65 years. Sensitivity analysis was also performed with lower and higher costs of LAAO. One-way sensitivity analysis illustrated with tornado diagram was used to assess parameter uncertainty and estimate which parameters had the greatest impact in the model. The parameter was identified as sensitive when either the range was the widest or the ICER value was greater than a threshold of US$50,000. The parameters in warfarin and LAAO strategies were pooled from two or more trials (Tables 1 and 2).
Probabilistic sensitivity analysis (PSA) using 10,000 Monte Carlo simulations was conducted to assess parameter uncertainty. The ranges of all parameters were obtained from published studies and calculating formula of 95 % confidence interval (Tables 1 and 2). A beta distribution was used for those parameters between 0 and 1. Cost data were non-negative quantitative data thus applying a gamma distribution.

Results

Base-case analysis

Under base-case conditions, LAAO was considered cost-effective compared with the 7 alternative pharmacological stroke prevention strategies for a hypothetical cohort of 65-year-old patient with non-valvular AF (Table 3 and Fig. 1). In descending sequence, the total costs of all strategies were apixaban ($53,315), rivaroxaban ($51,064), dabigatran 150 mg ($43,946), dabigatran 110 mg ($42,712), LAAO ($37,789), warfarin ($28,090), clopidogrel plus ASA ($26,287) and ASA alone ($12,877), respectively. LAAO was associated with the greatest QALYs (10.99 QALYs), followed by rivaroxaban (9.86 QALYs), warfarin (9.45 QALYs), apixaban (9 · 40 QALYs), dabigatran 150 mg (9 · 0 QALYs), dabigatran 110 mg (8.76 QALYs), clopidogrel plus ASA (6 · 29 QALYs) and ASA alone (6 · 12 QALYs).
Table 3
Lifetime results of total Costs, total QALYs and ICERs for each stroke prevention strategy (start age at 65-year-old patients)
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
Abbreviations: LAA left atrial appendage, ICER incremental cost-effectiveness ratio, QALY quality-adjusted life year, Extended dominance the alternative has a higher ICER than a more effective comparator
aLess costly and less effective strategy
bLess costly but more effective strategy
cMore costly but less effective strategy
The ICER per QALY gained for LAA occlusion compared with ASA alone, clopidogrel plus ASA and warfarin were $5,115, $2,447 and $6,298, respectively. LAAO was dominant (i.e. less costly but more effective) compared to dabigatran 110 mg, dabigatran 150 mg, apixaban, and rivaroxaban.

Sensitivity analysis

Sensitivity analysis demonstrated that LAAO remained cost-effective compared with other strategies when stroke risk was varied from CHADS2 score 0 to 6 (Table 4). In particular, dabigatran 110 mg, dabigatran 150 mg, apixaban and rivaroxaban were dominated by LAAO. When hemorrhage rate was varied by HAS-BLED score from 0 to 5 for anticoagulant drugs in the simulation model, LAAO remained cost-effective compared with each strategy. Varying the time horizon from 20 to 15, 10 and 5 years did not affect the cost-effectiveness of LAAO against all other treatment strategies except for warfarin (ICER: US$74,422) with a short 5 years time horizon. In tornado diagram, the results demonstrated the parameters with greatest impact were all-cause mortality of warfarin (−$32,048–$12,994) and all-cause mortality of LAAO ($3,631–$24,716), respectively (Fig. 2). PSA results demonstrated that the probability of LAAO strategy was the most cost-effective compared with other 7 strategies in 86.24 % of 10,000 Monte Carlo simulations at the threshold of US$50,000/QALY (Fig. 3).
Table 4
Sensitivity analysis of total Costs, total QALYs, and ICERs of LAA occlusion compared with each strategy by varying CHADS2 score, HAS-BLED score, time horizons, and LAA occlusion costs
 
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
     
Abbreviations: LAAO left atrial appendage occlusion, ICER incremental cost-effectiveness ratio, QALY quality-adjusted life year, CHADS 2 congestive heart failure, hypertension, age > 75, diabetes mellitus, and previous stroke/transient ischemic attack, HAS-BLED hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), drugs/alcohol concomitantly, ICER calculated as the difference in cost divided by the difference in QALYs for each therapy compared with LAAO strategy, Dominated LAAO is less costly but more effective strategy compare with each strategy

Discussion

Previous study has demonstrated the cost-effectiveness of LAAO, dabigatran and warfarin in the management of NVAF [28]. This was the first comprehensive analysis to compare the cost-effectiveness between seven pharmacological strategies including newer oral anticoagulants and transcatheter LAA occlusion for stroke prevention in NVAF patients. We demonstrated that LAAO was associated with the highest QALYs gained and the lowest ICER per QALY gained compared to 7 other pharmacological regimens in the prevention of AF-related stroke. Sensitivity analysis also demonstrated that LAAO remained cost-effective compared with all 7 alternative strategies across the spectrum of stroke risks, bleeding risk and time horizon.
Atrial fibrillation is a growing problem in an aging society. It causes >50 000 strokes and $12 billion in medical expenditure each year in United States. Warfarin used to be the standard of care in preventing stroke but it is difficult to be used conveniently and safely [29]. NOACs may be comparable to warfarin in terms of clinical efficacy but the benefit does not come without risk of bleeding. Transcatheter LAAO potentially reduces both risks of stroke and bleeding associated with long-term anticoagulation and the 2012 European Society of Cardiology Guidelines recommended such intervention can be considered in patients with high stroke risk and contraindications for oral anticoagulants [30]. A few studies attempted to evaluate the cost-effectiveness of these newer stroke preventive strategies. One key analysis based on the RE-LY study [3] showed the ICERs of dabigatran 110 mg and 150 mg compared with warfarin were US$16,147–115,129 and US$39,680–263,543, respectively, which were much higher compared to the ICER for LAAO in our current study. SM Singh, A Micieli and HC Wijeysundera [8] demonstrated LAAO was cost-effective as compared to dabigatran and warfarin but they did not address the impact of other commonly used NOACs and the treatment duration on the cost-effective performance of the device therapy [28]. In current analysis, we demonstrated the superior cost-effectiveness of the device compared to other NOACs, which is independent of stroke risk (CHADS2 score), bleeding risk (HAS-BLED score) and treatment duration (i.e. device strategy was cost-effective even at 5 year follow-up). In particular, LAAO was considered cost-effective comparing to all alternative strategies when HAS-BLED score and CHADS2 score were varied. Considering most adverse events occur during and shortly after device implantation [5, 20], while events with oral anticoagulants develop continuously over time, our findings may provide additional insights in selecting specific therapy for individual patient groups.
Three endovascular LAA occluding devices have been widely used in humans and many other new devices are under pre-clinical evaluation [31]. The PLAATO device was the oldest with reported favorable clinical results up to 5 years but the device has been withdrawn from the market because of financial considerations [32]. PROTECT-AF trial [5] showed the WATCHMAN device was non-inferior to warfarin in reducing ischemic stroke in AF patients with CHADS2 score of ≥1 and the device arm was associated with less hemorrhagic stroke. Early registry results with Amplatzer Cardiac Plug (St Jude Medical Inc, US), consistently reported a high implantation success rate >95 %, implying its wide applicability to AF patients [6, 33]. The longest follow-up data were also shown to demonstrate the promising results with Amplatzer device in AF patients for stroke prevention [33]. While the device therapy addresses both the concerns of inconvenience (no issue with drug interaction, blood monitoring and compliance) and safety (bleeding) associated with long term oral anticoagulant usage, it also has shortcomings in particular procedural-related complications [5, 6, 12, 14] and the risks of having incomplete LAAO and thrombus formation on the device during long-term follow up. The costs of managing these events needed to be studied especially when the device strategy has been widely adopted in in-experienced centers.

Limitations

There are a number of limitations of the current study. Firstly, there was no directly comparative trial between LAAO and oral anticoagulation. Secondly, the base-case values of the current model simulation were derived from individual clinical trials from different countries and healthcare systems with variable costs of management. Thirdly, a number of base-case assumptions were necessary when trial data were lacking. Fourthly, data from randomized clinical trials could not be generalizable to “real world” clinical practice. It should also be noted that only direct medical cost was considered in the analysis. Fifthly, we assumed that warfarin was discontinued after 45 days post LAAO although some patients may require warfarin beyond 45 days when TEE confirmed clots or device leak. Furthermore, the long-term follow-up data for the newer LAAO devices were obtained from a single study with 10-year follow up of Amplatzer left atrial appendage occlusion [33], it may add to model uncertainties and parameter uncertainties in the results, however, sensitivity analyses demonstrated the robustness of study results.

Conclusions

In conclusion, our Markov analytic model demonstrated that transcatheter LAAO was cost-effective compared to ASA alone, clopidogrel plus ASA, warfarin, dabigatran 110 mg, dabigatran 150 mg, rivaroxaban and apixaban for stroke prevention in patients with NVAF.

Acknowledgements

We would like to acknowledge Markus Siebert and Maria Koullick (St. Jude Medical, USA) who gave us invaluable advice regarding healthcare costs for LAA occlusion in the United States.

Availability of data and materials

The data sharing for this project is not feasible since we are using the Treeage software to simulate the analysis.

Authors’ contributions

IC and RT analyzed data and prepared report for this project. VL was responsible for study design, interpretation of data and logistics of this project. BY and YYL were responsible for study design and interpretation of data. MGK and JWP provided consultation on study design and interpretation of data. All authors read and approved the final manuscript.

Competing interests

Dr Yat-Yin Lam is the consultant and clinical proctor for St Jude Medical and Boston Scientific LAA occluders. Dr Jai-Wun Park is also the clinical proctor for St Jude Medical LAA occluder. Prof Vivian Lee has received sponsorship from Boehringer Ingelheim (HK) Ltd previously. The remaining authors have no conflicts of interest to declare.
Not applicable.
The study did not require ethic approval since it was a computer model simulation.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
Literatur
1.
Zurück zum Zitat Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983–8.CrossRefPubMed Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983–8.CrossRefPubMed
2.
Zurück zum Zitat Active Investigators, Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, Yusuf S. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009;360(20):2066–78.CrossRef Active Investigators, Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, Yusuf S. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009;360(20):2066–78.CrossRef
3.
Zurück zum Zitat Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, et al. Dabigatran versus Warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.CrossRefPubMed Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, et al. Dabigatran versus Warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.CrossRefPubMed
4.
Zurück zum Zitat Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.CrossRefPubMed Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.CrossRefPubMed
5.
Zurück zum Zitat Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM, Sick P, PA Investigators. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet. 2009;374(9689):534–42.CrossRefPubMed Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM, Sick P, PA Investigators. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet. 2009;374(9689):534–42.CrossRefPubMed
6.
Zurück zum Zitat Park JW, Bethencourt A, Sievert H, Santoro G, Meier B, Walsh K, Lopez-Minquez JR, Meerkin D, Valdes M, Ormerod O, et al. Left atrial appendage closure with Amplatzer cardiac plug in atrial fibrillation: initial European experience. Catheter Cardiovasc Interv. 2011;77(5):700–6.CrossRefPubMed Park JW, Bethencourt A, Sievert H, Santoro G, Meier B, Walsh K, Lopez-Minquez JR, Meerkin D, Valdes M, Ormerod O, et al. Left atrial appendage closure with Amplatzer cardiac plug in atrial fibrillation: initial European experience. Catheter Cardiovasc Interv. 2011;77(5):700–6.CrossRefPubMed
7.
Zurück zum Zitat Reddy VY, Akehurst RL, Armstrong SO, Amorosi SL, Beard SM, Holmes Jr DR. Time to cost-effectiveness following stroke reduction strategies in AF: warfarin versus NOACs versus LAA closure. J Am Coll Cardiol. 2015;66(24):2728–39.CrossRefPubMed Reddy VY, Akehurst RL, Armstrong SO, Amorosi SL, Beard SM, Holmes Jr DR. Time to cost-effectiveness following stroke reduction strategies in AF: warfarin versus NOACs versus LAA closure. J Am Coll Cardiol. 2015;66(24):2728–39.CrossRefPubMed
8.
Zurück zum Zitat Singh SM, Micieli A, Wijeysundera HC. Economic evaluation of percutaneous left atrial appendage occlusion, dabigatran, and warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Circulation. 2013;127(24):2414–23.CrossRefPubMed Singh SM, Micieli A, Wijeysundera HC. Economic evaluation of percutaneous left atrial appendage occlusion, dabigatran, and warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Circulation. 2013;127(24):2414–23.CrossRefPubMed
9.
Zurück zum Zitat Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York: Oxford University Press; 1996. Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York: Oxford University Press; 1996.
10.
Zurück zum Zitat Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation. 2011;123(22):2562–70.CrossRefPubMed Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation. 2011;123(22):2562–70.CrossRefPubMed
11.
Zurück zum Zitat Reddy VY, Mobius-Winkler S, Miller MA, Neuzil P, Schuler G, Wiebe J, Sick P, Sievert H. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology). J Am Coll Cardiol. 2013;61(25):2551–6.CrossRefPubMed Reddy VY, Mobius-Winkler S, Miller MA, Neuzil P, Schuler G, Wiebe J, Sick P, Sievert H. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology). J Am Coll Cardiol. 2013;61(25):2551–6.CrossRefPubMed
12.
Zurück zum Zitat Reddy VYMD, Holmes DMD, Doshi SKMD, Neuzil PMDP, Kar SMD. Safety of percutaneous left atrial appendage closure: results from the watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the continued access registry. Circulation. 2011;123(4):417–24.CrossRefPubMed Reddy VYMD, Holmes DMD, Doshi SKMD, Neuzil PMDP, Kar SMD. Safety of percutaneous left atrial appendage closure: results from the watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the continued access registry. Circulation. 2011;123(4):417–24.CrossRefPubMed
13.
Zurück zum Zitat Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.CrossRefPubMed Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.CrossRefPubMed
14.
Zurück zum Zitat Holmes Jr DR, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY. Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014;64(1):1–12.CrossRefPubMed Holmes Jr DR, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY. Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014;64(1):1–12.CrossRefPubMed
15.
Zurück zum Zitat Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS, Wang PJ, Turakhia MP. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med. 2011;154(1):1–11.CrossRefPubMed Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS, Wang PJ, Turakhia MP. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med. 2011;154(1):1–11.CrossRefPubMed
16.
Zurück zum Zitat Harrington AR, Armstrong EP, Nolan Jr PE, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke. 2013;44(6):1676–81.CrossRefPubMed Harrington AR, Armstrong EP, Nolan Jr PE, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke. 2013;44(6):1676–81.CrossRefPubMed
17.
Zurück zum Zitat O'Brien CL, Gage BF. Costs and effectiveness of ximelagatran for stroke prophylaxis in chronic atrial fibrillation. JAMA. 2005;293(6):699–706.CrossRefPubMed O'Brien CL, Gage BF. Costs and effectiveness of ximelagatran for stroke prophylaxis in chronic atrial fibrillation. JAMA. 2005;293(6):699–706.CrossRefPubMed
18.
Zurück zum Zitat Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Halperin JL, Holmes D. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-Year Follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) Trial. Circulation. 2013;127(6):720–9.CrossRefPubMed Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Halperin JL, Holmes D. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-Year Follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) Trial. Circulation. 2013;127(6):720–9.CrossRefPubMed
19.
Zurück zum Zitat Bayard YL, Omran H, Neuzil P, Thuesen L, Pichler M, Rowland E, Ramondo A, Ruzyllo W, Budts W, Montalescot G, et al. PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) for prevention of cardioembolic stroke in non-anticoagulation eligible atrial fibrillation patients: results from the European PLAATO study. EuroIntervention. 2010;6(2):220–6.CrossRefPubMed Bayard YL, Omran H, Neuzil P, Thuesen L, Pichler M, Rowland E, Ramondo A, Ruzyllo W, Budts W, Montalescot G, et al. PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) for prevention of cardioembolic stroke in non-anticoagulation eligible atrial fibrillation patients: results from the European PLAATO study. EuroIntervention. 2010;6(2):220–6.CrossRefPubMed
20.
Zurück zum Zitat Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Kar S, Halperin JL, Whisenant B, Swarup V et al.: Long-term PROTECT-AF analysis: Watchman attains efficacy superiority over warfarin in AF. In: Heart Rhythm Society (HRS) 34th Annual Scientific Sessions. Denver, Colorado; May 2013. Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Kar S, Halperin JL, Whisenant B, Swarup V et al.: Long-term PROTECT-AF analysis: Watchman attains efficacy superiority over warfarin in AF. In: Heart Rhythm Society (HRS) 34th Annual Scientific Sessions. Denver, Colorado; May 2013.
21.
Zurück zum Zitat Gage BF, Cardinalli AB, Owens DK. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med. 1996;156(16):1829–36.CrossRefPubMed Gage BF, Cardinalli AB, Owens DK. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med. 1996;156(16):1829–36.CrossRefPubMed
22.
Zurück zum Zitat Sullivan PW, Ghushchyan V. Preference-Based EQ-5D index scores for chronic conditions in the United States. Med Decis Making. 2006;26(4):410–20.CrossRefPubMedPubMedCentral Sullivan PW, Ghushchyan V. Preference-Based EQ-5D index scores for chronic conditions in the United States. Med Decis Making. 2006;26(4):410–20.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Fryback DG, Dasbach EJ, Klein R, Klein BE, Dorn N, Peterson K, Martin PA. The Beaver Dam Health Outcomes Study: initial catalog of health-state quality factors. Med Decis Making. 1993;13(2):89–102.CrossRefPubMed Fryback DG, Dasbach EJ, Klein R, Klein BE, Dorn N, Peterson K, Martin PA. The Beaver Dam Health Outcomes Study: initial catalog of health-state quality factors. Med Decis Making. 1993;13(2):89–102.CrossRefPubMed
24.
Zurück zum Zitat Thomson R, Parkin D, Eccles M, Sudlow M, Robinson A. Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation. Lancet. 2000;355(9208):956–62.CrossRefPubMed Thomson R, Parkin D, Eccles M, Sudlow M, Robinson A. Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation. Lancet. 2000;355(9208):956–62.CrossRefPubMed
27.
Zurück zum Zitat Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093–100.CrossRefPubMed Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093–100.CrossRefPubMed
28.
Zurück zum Zitat Lam YY, Ma TKW, Yan BP. Alternatives to chronic warfarin therapy for the prevention of stroke in patients with atrial fibrillation. Int J Cardiol. 2011;150(1):4–11.CrossRefPubMed Lam YY, Ma TKW, Yan BP. Alternatives to chronic warfarin therapy for the prevention of stroke in patients with atrial fibrillation. Int J Cardiol. 2011;150(1):4–11.CrossRefPubMed
29.
Zurück zum Zitat Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–47.CrossRefPubMed Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–47.CrossRefPubMed
30.
Zurück zum Zitat Cruz-Gonzalez I, Yan BP, Lam YY. Left atrial appendage exclusion: state-of-the-art. Catheter Cardiovasc Interv. 2010;75(5):806–13.CrossRefPubMed Cruz-Gonzalez I, Yan BP, Lam YY. Left atrial appendage exclusion: state-of-the-art. Catheter Cardiovasc Interv. 2010;75(5):806–13.CrossRefPubMed
31.
Zurück zum Zitat Lam YY, Yip GW, Yu CM, Chan WW, Cheng BC, Yan BP, Clugston R, Yong G, Gattorna T, Paul V. Left atrial appendage closure with AMPLATZER cardiac plug for stroke prevention in atrial fibrillation: initial Asia-Pacific experience. Catheter Cardiovasc Interv. 2012;79(5):794–800.CrossRefPubMed Lam YY, Yip GW, Yu CM, Chan WW, Cheng BC, Yan BP, Clugston R, Yong G, Gattorna T, Paul V. Left atrial appendage closure with AMPLATZER cardiac plug for stroke prevention in atrial fibrillation: initial Asia-Pacific experience. Catheter Cardiovasc Interv. 2012;79(5):794–800.CrossRefPubMed
32.
Zurück zum Zitat Gage BF, van Walraven C, Pearce L, Hart RG, Koudstaal PJ, Boode BS, Petersen P. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation. 2004;110(16):2287–92.CrossRefPubMed Gage BF, van Walraven C, Pearce L, Hart RG, Koudstaal PJ, Boode BS, Petersen P. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation. 2004;110(16):2287–92.CrossRefPubMed
33.
Zurück zum Zitat Nietlispach F, Gloekler S, Krause R, Shakir S, Schmid M, Khattab AA, Wenaweser P, Windecker S, Meier B. Amplatzer left atrial appendage occlusion: single center 10-year experience. Catheter Cardiovasc Interv. 2013;82(2):283–9.CrossRefPubMed Nietlispach F, Gloekler S, Krause R, Shakir S, Schmid M, Khattab AA, Wenaweser P, Windecker S, Meier B. Amplatzer left atrial appendage occlusion: single center 10-year experience. Catheter Cardiovasc Interv. 2013;82(2):283–9.CrossRefPubMed
Metadaten
Titel
Cost-effectiveness analysis of left atrial appendage occlusion compared with pharmacological strategies for stroke prevention in atrial fibrillation
verfasst von
Vivian Wing-Yan Lee
Ronald Bing-Ching Tsai
Ines Hang-Iao Chow
Bryan Ping-Yen Yan
Mehmet Gungor Kaya
Jai-Wun Park
Yat-Yin Lam
Publikationsdatum
01.12.2016
Verlag
BioMed Central
Erschienen in
BMC Cardiovascular Disorders / Ausgabe 1/2016
Elektronische ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-016-0351-y

Weitere Artikel der Ausgabe 1/2016

BMC Cardiovascular Disorders 1/2016 Zur Ausgabe

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.