La chiusura dell’auricola per la prevenzione dello stroke ... · La chiusura dell’auricola per...
Transcript of La chiusura dell’auricola per la prevenzione dello stroke ... · La chiusura dell’auricola per...
Antonio Manari U.O. Cardiologia Interventistica
Azienda Ospedaliera Santa Maria Nuova Reggio Emilia
La chiusura dell’auricola per la prevenzione dello stroke nel
paziente con FA
S. Margherita 17 febbraio 2012
Istituto di Ricovero e Cura a Carattere Scientifico
Who Gets Atrial Tachyarrhythmias?Atrial Fibrillation Demographics by Age
Feinberg WM, Blackshear JL, Laupacis A. Arch Intern Med. 1995;155:469-473
0%
5%
10%
15%
20%
25%
30%
35%
40%
50-59 60-69 70-79 80-89
Prevalence of AF
Strokes Attributable toAF
Prevalence of AF and Strokes attributable to AF by age.
Framingham Study, Wolf, 1991
Efficacy of Antithrombotic Treatment in Non-ValvularAtrial Fibrillation
META ANALYSIS• 26 Trials
• 28,044 Patients
• Mean Age 71 Years
• Mean Follow up 1.5 years
Comparison Trials Patients Reduction in Stroke
Warfarin Vs. Control 6 2,900 64%
Antiplatelet agents vs. control 8 4,876 22%
Warfarin vs. Antiplatelet 12 12,963 39%
Har RG, Ann Intern Med 2007; 146:857-86
warfarin better control better
AFASAK
SPAF
BAATAF
CAFA
SPINAF
EAFT
100% 50% 0 -50% -100%
Aggregate
Anticoagulation in atrial fibrillationStroke risk reductions
Stroke:RRR 62%
All-cause mortality: RRR 26%
Severe bleedings:1.2%/year
Warfarin is the gold standard in patients with atrialfibrillation.
Eur Heart J 2010
ESC Guidelines 2010 on the management of Atrial Fibrillation
“REAL WORLD” USE OF WARFARIN IN AF PATIENTS WITHOUT CONTRAINDICATIONS”
%
0 10 20 30 40 50 60Bath et al, 1993
Lip et al, 1994Stafford & Singer, 1996
Albers et al, 1997Whittle et al, 1997
Gurwitz et al, 1997Brass et al, 1997
Sudlow et al, 1998CQInv, 1998
Samsa et al, 2000McCormick et al, 2001
Harrold et al, 2002
2936
3220
4431
282324 34
4253
44,3
58,1 60,7 57,3
35,4
010203040506070
<55 55-64 65-74 75-84 85
Non-Valvular Atrial Fibrillation Warfarin use in AF Patients by Age
%
Ann Int Med 131(12), 1999
• Only 55% of AF patients with no contraindications have evidence of warfarin use in previous 3 months
• Other studies cite warfarin use in AF patients from 17-50%• Elderly patients with increased absolute risk least likely to be taking warfarin• Contraindications 30-40%
Age-related trends in AF
Age, years69-79 80-89 >89
100
80
60
40
20
0
Wolf PA, Arch Intern Med 1987; 147:1561-4White RH, Am J Med 1999; 106:165-71
Unmet need
Narrow anticoagulant therapeutic window
Stroke risk increases at INR < 2Bleeding risk increases at INR >3
Hylek EM et al, N Engl J Med 1996; 335: 540-546
11
0 20 40 60 80 100
Non-Valvular Atrial Fibrillation Adequacy of Anticoagulation in Clinic
%Bungard, Pharmacotherapy 20:1060, 2001
Low INR <1.6
TherapeuticINR 2-3
High INR >3.2
Efficacy 4-fold
ORAL ANTICOAGULATION AND RISK OF BLEEDING
ISCOAT Study 2,745 pts
Palareti et al, Arch Intern Med 2000; 160: 470-478
0
2
4
6
8
10
ELDERLY PTS YOUNG PTS
2.1 1.1
9.9
6.6
Major bleeds All bleedsN= 461
Age > 75 (79.9)N= 461
Age < 70 (56.5)
PT / Y
EAR
%
ns
RCT’s & WarfarinINR al momento dello Stroke
AFASAK SPAF I BAATAF SPINAFCAFA1.0
2.0
3.0
4.01.71.61.51.41.31.21.11.0
INRRatio
PTRatio
(ISI 2.4)
ACCP raccomandazioni: INR: 2.0–3.0
1.8
Target range per ogni studio
Risk adjusted percent time in therapeutic range as a quality indicator for out-patient oral anticoagulation: results of the Veterans Affairs Study to ImproveAnticoagulation (VARIA).
Rose AJ, Circ Cardiovasc Qual Outcomes 2011;4:22-9
In a recent analysis of anticoagulation management involving more than 120,000 patients in the Veterans Affairshealth care system, the mean proportion of time in the therapeutic range was 58%, with significant variationacross Sites.
Percentuale di tempo con INR in rangein RCTs in era contemporanea
0102030405060708090
100
Rivaroxaban Apixaban Dabigatran
5562,2 64
%
(2011) (2011) (2009)
15
19
23
27
Rivaroxaban Warfarin
23,722,2
Rocket-AF% sospensione del farmaco
1519232731
Apixaban Warfarin
25,327,5
ARISTOTLE%sospensione del farmaco
15
19
23
Dab 110 Dab 150 Warfarin
21 21
17
RE LY%sospensione del farmaco
Aderenza alla terapia nei RCTs in era contemporanea
Rocket-AF
• The median duration of treatment exposure was 590 days; the medianfollow-up period was 707 days
15
19
23
27
Rivaroxaban Warfarin
23,722,2
% sospensione del farmaco
0
1
2
3
4
5
6
Dab 110 Dab 150 Warfarin
0,82 0,89
2,432,292,6
3,25
4,435,1
4,37
< 65 65-74 >75
0
1
2
3
4
5
6
Dab 110 Dab 150 Warfarin
5,29 5,44 5,41
2,893,33
3,76
1,532,09 2,36
Cl Crea<50 Cl Crea50-70 Cl Crea >80
0
1
2
3
4
5
6
Dab 110 Dab 150 Warfarin
4,34,92
5,95
2,91 3,133,75
2,56
4,013,34
Peso<50 Peso50-99 Peso100
ARISTOTLEApixaban vs Warfarin
a high risk of bleeding (e.g., active peptic ulcer disease, a plateletcount of <100,000 per cubic millimeter or hemoglobin level of <10 g per deciliter, stroke within the previous 10 days, documentedhemorrhagic tendencies, or blood dyscrasias),
Prevenzione dello stroke emboliconella Fibrillazione Atriale
Mechanism of Stroke in Patients with AF
Devices per la chiusura
percutanea
Left atrial appendage closure
Left atrial appendage closure
Left atrial appendage closure
Left atrial appendage closure
Left atrial appendage closure
Left atrial appendage closure
Left atrial appendage closure
Left atrial appendage closure
Left atrial appendage closure
Left atrial appendage closure
Left atrial appendage closure
April 23, 200941
PROTECT-AF TrialEnrollment Summary
Implant successful in 90.9%(408/449) of attempts
* One or more of the release criteria of acceptable device position, in-situ size (compression), stability, and LAA seal were not met for device release.
Included In Primary Analysis
Randomized PatientsN=707
WarfarinControl Group
N=244
WATCHMANDevice Group
N=463
No AttemptN=14
Device Implanted N=408
Unable to ImplantN=41
Device Release Criteria Not Met*
N=29
N=12
WarfarinStartedN=241
Warfarin NeverStarted
N=3
Implant Attempted
N=449
OtherN = 3
N=10
Window For Procedure Lapsed
Patient Died Before Procedure
N=1
Procedural Event
0,8
0,9
1
Primary Efficacy Results(CV deaths, stroke, systemic embolization)
707 pts with non-valvular AF (CHADS2 ≥1) E
vent
-free
pr
obab
ility
Days
Events Total Rate Events Total Rate Rel. Risk Non-Cohort (no.) pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI) inferiority Superiority
900 pt-yr 20 582.3 3.4 16 318.0 5.0 0.68 0.998 0.837(2.1, 5.2) (2.8, 7.6) (0.37, 1.41)
Device ControlPosterior
Probabilities
Randomization allocation (2 device : 1 control)
ITT Cohort:patients analyzed based on their randomly assigned group (regardless of treatment received)
244 147 52 12463 270 92 22
WATCHMAN
Control
0,7
0,8
0,9
1
0 365 730 1095
All Stroke
ITT cohort: patients analyzed based on their randomly assigned group (regardless of treatment received)E
vent
-free
pro
babi
lity
Days244 147 52 12463 270 92 22
900 patient-year analysis
Events Total Rate Events Total Rate RR Non- SuperiorityCohort eve pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI) inferiority
600 14 409.3 3.4 8 223.6 3.6 0.96 0.927 0.488pt-yr (1.9, 5.5) (1.5, 6.3) (0.43, 2.57)
900 15 582.9 2.6 11 318.1 3.5 0.74 0.998 0.731pt-yr (1.5, 4.1) (1.7, 5.7) (0.36, 1.76)
Device Control Posterior probabilities
Randomization allocation (2 device:1 control)
Control
Device
3001664-2
Hemorrhagic Stroke
ITT cohort: patients analyzed based on their randomly assigned group (regardless of treatment received)E
vent
-free
pro
babi
lity
Days244 147 53 12463 275 95 23
900 patient-year analysis
Events Total Rate Events Total Rate RR Non- SuperiorityCohort (no.) pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI) inferiority
600 1 416.7 0.2 4 224.7 1.8 0.13 0.998 0.986pt-yr (0.0, 0.9) (0.5, 3.9) (0.00, 0.80)
900 1 593.6 0.2 6 319.4 1.9 0.09 >0.999 0.998pt-yr (0.0, 0.6) (0.7, 3.7) (0.00, 0.45)
Device Control Posterior probabilities
Randomization allocation (2 device:1 control)
Control
Device
3001664-2
Events Total Rate Events Total Rate Rel. RiskCohort (no.) pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI)
900 pt-yr 48 554.2 8.7 13 312.0 4.2 2.08(6.4, 11.3) (2.2, 6.7) (1.18, 4.13)
0,8
0,9
1
Intent-to-TreatPrimary Safety Results
Eve
nt-fr
ee
prob
abili
ty
Days
Device Control
ITT Cohort:patients analyzed based on their randomly assigned group (regardless of treatment received)
244 143 51 11463 261 87 19
WATCHMAN
Control
Randomization allocation (2 device : 1 control)
LAA occlusion
Atrial fibrillation
High risk of stroke– Contraindication to OAC– High risk of bleeding with OAC– Difficult to maintain INR within the therapeutic range– Poor compliance– Difficulty to manage the patient because ol ogistic problems