Linker hartoor sluiting: WATCHMAN Y.J. Stevenhagen, cardioloog, Medisch Spectrum Twente
DRES
1
Inhoud Workshop • • • • • • •
Casus Achtergrond behandeling atriumfibrilleren Waarom linker hartoor afsluiting Procedure en interpretatie van images Klinisch bewijs voor de Watchman Conclusies Demo materiaal
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Casus 1 • • • • •
Man, 60 jaar Paroxysmaal atriumfibrilleren Diabetes Hypertensie Vaatlijden
• CHA2DS2VASc score 3 • Gebruik VKA 3
Intracerebrale bloeding • INR 3.2 • VKA stop tijdelijk
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Staken VKA • 2 maal TIA • MRI ischaemisch CVA • Wat zijn je opties?
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Casus 2 • • • • •
Vrouw 71 jaar Persisterend atriumfibrilleren Nierfunctiestoornissen Hypertensie CHA2DS2Vasc score 3
• Recidiverende TIA’s meerdere stroomgebieden onder adequate VKA instelling • Wat zijn je opties? 6
Achtergrond • Patienten met atriumfibrilleren • 5 keer meer risico op CVA • Ernstiger CVA • Occlusie grotere vaten • Groter ischaemisch gebied • Hogere mortaliteit • Frequent recidief • 40% relatieve/absolute contra-‐indicatie OAC • 90% thrombus afkomstig vanuit linker hartoor 7
Waarom linker hartoorsluiting
8
Stroke profylaxe • Stroke preventie • Vermijden bloedingen
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Behandeling opties AF
en/of Stroke preventie
Ablatie
Pacing VKA
NOAC
Interventie
Rate controle
Chirurgisch
LAA Clip
Percutaan LAAC 10
CHA2DS2VASc score CHA2DS2-VASc
Annual Risk of Stroke1,2 18%
C
Congestive heart failure
H
Hypertension
1
A
Age ≥ 75
2
D
Diabetes mellitus
1
S
Stroke/TIA
2
V A Sc
Vascular disease Age 65-74 Sex category (female)
1
15,2
15%
13%
9,8
10%
9,6
1 1 1
6,7 6,7
5% 4,0 3,2
3%
2,2 1,3
Maximum Score:
9
0%
0
1
2
3
4
5
6
7
8
9
11
1 jaars bloedingsrisico HAS-BLED
H
Hypertension
A
Renal / Liver dysfunction
S
Stroke
1
B
Bleeding
2
L
Labile INRs
E D
1
Keuze voor embolie profylaxe: Balans tussen stroke risico en risico op grote bloedingen
1 or 2 Score
Bleeds per 100 patient-years
1
0
1.13
Elderly (age≥ 65 years)
1
1
1.02
Drugs or alcohol abuse
1 or 2
2
1.88
3
3.74
4
8.70
Maximum Score:
9
12
Risicoreductie CVA
13
ESC guideline
14
VKA praktijk 33% 67%
N= 5333 EuroHeart survey1
VKA
No anticoagulation
15
VKA praktijk Time outside therapeutic INR • INR • Smalle range 2-‐3 36 • Interactie voedsel medicatie 64 • Frequente monitoring • Bloedingen Time in therapeutic INR • Hospitalisering
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NOAC • Nadeel
• Voordeel
• Bloeding nagenoeg evenveel
• Geen monitoring • Goede stroke preventie
• 10% gestopt na 1 jaar ivm bijwerkingen
• Vermindering intracraniele bloedingen Study
RE-LY1
ROCKET-AF2
ARISTOLE3
Treatment
Major Bleeding
Hemorrhagic
Stroke
Discontinuation
in the study
Dabigatran (110mg)
2.71 %
0.12 %
20.7 %
Dabigatran (150mg)
3.11 %
0.10 %
21.2 %
Warfarin Rivaroxaban
3.36 % 3.6 %
0.38 % 0.5%
16.6 % 23.7%
Warfarin
3.4 %
0.7 %
22.2 %
Apixaban
2.13 %
0.24 %
25.3 %
Warfarin
3.09 %
0.47 %
nc
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WATCHMAN™ Procedure
Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Indications, and instructions for use health can be found product labeling supplied with each device. Indications,contraindications, contraindications, and for use can in bethe found in registrations. the product labeling supplied with 2014 each device. Information for the use onlywarnings in warnings countries with instructions applicable authority product SH-218301-AA JAN Information for the use only in countries with applicable health authority product registrations. SH-218301-AA JAN 2014 Information for the use only in countries with applicable health authority product registrations.
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Hartoor anatomie
Cactus (30%)
Windstock (19%)
Chicken Wing (30%)
Cauliflower (3%) 19
Watchman procedure
20
Watchman LAAC device Nitinol Frame ▪ ▪
Radially expands to maintain position in LAA Contour shape
accommodates
most LAA anatomies
160 Micron Membrane ▪ ▪ ▪
Polyethylene terephthalate (PET) cap Designed to block emboli from exiting the LAA Intended to promote healing process
Anchors
Sizes:
10 Active fixation anchors around device perimeter designed to engage LAA tissue for stability and retention
21, 24, 27, 30, 33 mm (Diameter)
21
Watchman device
22
Watchman System Components Delivery System
Access Sheath Double Curve
Deployment Knob
Hemostasis Valve
Single Curve Core Wire
Preassembled 12Fr (4 mm) Delivery System Compatible with all device sizes
>> Designed for Safety and Ease of Use << ▪ Double or Single Curve styles ▪ 14F O.D. (4.7 mm), 12F I.D. (4 mm) ▪ 75 cm working length
Preloaded Device Saves time
Distal Marker Band Guides placement
23
Implantatie procedure
LAA dimensie bepaling • TEE • Bevestig afwezigheid trombus • Metingen TEE • 0, 45, 90, 135 graden • Lengte LAA
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Implantatie procedure
Sheat in LAA • Pigtail voor manipulatie • Selectieve angiogram • Zo distaal mogelijk
Marker bands
25
Implantatie procedure
Sheat plaatsing Access Sheath Marker Band
Loaded Device Length
21mm
20.2mm
24mm
22.9mm
27mm
26.5mm
30mm
29.4mm
33mm
31.5mm
• Radiopaque marker bands bepalen diepte sheet in LAA • Allignment marker band met ostium afhankelijk device lengte 26
Implantatie procedure
Device positioneren • Unsheat device rustig • NIET naar voren verplaatsen
27
Implantatie procedure
Optimale positie
28
Implantatie procedure
Release criteria (PASS) All criteria must be met prior to device release
✓ Position – device is distal to or at the ostium of the LAA ✓ Anchor – (stability) fixation barbs engaged / device is stable ✓ Size – device is compressed at least 8-20% of original size ✓ Seal - device spans ostium, all lobes of LAA are covered •
If necessary, device can be recaptured (partial or full) 29
Implantatie procedure
Lekkage
• Jet moet < 5mm • Tracht repositonering, partiele recapture of volledige recapture 30
Positie Watchman
31
Implantatie procedure
Samenvatting
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Klinisch bewijs voor de Watchman 2008 CAP Registry
Endpoints: Collect additional safety and efficacy data to be pooled with PROTECT AF
Incl/Excl: same as PROTECT AF
2010 PREVAIL
2002 Pilot
Endpoints: Feasibility and Safety Comparison: Nonrandomzed Incl/Excl: CHADS2≥1, able to tolerate warfarin
Endpoint: Safety and Efficacy
Comparison: warfarin Incl/Excl: CHADS2≥2, some exceptions for CHADS2=1
no clopidegrel 7 days prior to procedure
2012
2005 PROTECT AF
Endpoints: Safety and Efficacy
Comparison: warfarin
Incl/Excl: CHADS2 ≥ 1,
able to tolerate warfarin
ESC Guidelines
& Expanded Indication
2009 ASAP
Endpoint: Efficacy
Comparison: CHADS2 score
expected stroke rate
Incl/Excl: intolerant or
contra-indicated for warfarin
2013 EWOLUTION*
1000 patient Real Life Registry in Europe Endpoint: Additional information
in a real-world setting
Incl/Excl: All comers
* In planning phase
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Studies • > 2000 ptn in meerdere gerandomiseerde trials • > 4000 patient jaren follow-‐up Study
Patients
Sites
Pilot
66
8
402 patient years of follow-up 6 years of follow-up
PROTECT AF
707
59
1500 patient years of follow-up 2.3 years average follow-up per patient
CAP (Continued
Access Registry)
460
26
Significantly improved safety results
ASAP
150
4
Treat patients contra-indicated for warfarin
EVOLVE
69
3
Evaluate design changes of a non-commercialized WATCHMAN device
PREVAIL
453
41
Same endpoints as PROTECT AFRevised inclusion/exclusion criteria Results presented in March 2013
CAP2
579
48
Prospective, multicenter, single-arm registry (PROTECT AF or PREVAIL)
Total Patients:
Comments
2484
34
PROTECT AF
Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
35 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information contained herein for distribution outside the USA, France and Japan only. and only in countries with applicable health authority product registrations. SH-231502-AA MAR 2014 © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
WATCHMAN™ PROTECT AF Study Objective
Effectiveness and safety of LAA closure for prevention of stroke in comparison to Coumadin for non-valvular A-fib patients
Study Design
Prospective, randomized (2:1), non-inferiority trial of LAA closure vs. warfarin in A-fib patients for prevention of stroke
Primary Endpoint
Efficacy: Composite end point of stroke, cardiovascular death or systemic embolization Safety: Major bleeding, device embolization or pericardial effusion n = 707
Patient Population Mean CHADS2=2.2 Mean Follow-Up
1065 Patient-years, 18 months (Holmes, et al., Lancet 2009; 374: 534–42) 1588 Patient-years, 2.3±1.1 years (Reddy, et al., Circ 2013) 2,621 patient-years, 4 years (Reddy, et al., HRS LBCT 2013)
Number of Sites
59 in the United States and Europe
Holmes, et al., Lancet 2009; 374: 534–42 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
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WATCHMAN™ PROTECT AF 4 Yrs. WATCHMAN Observed Rate per 100 pt-yrs
Warfarin Observed Rate per 100 pt-yrs
% Reduction (vs Warfarin)
Primary Endpoint
2.3
3.8
40%
SUPERIOR
CV Death
1.0
2.4
60%
SUPERIOR
All-cause Death
3.2
4.8
34%
SUPERIOR
Events in PROTECT AF trial at 2,621 patient years 40% lower
32% lower
60% lower
PS > 82.5%
P=0.0045
WATCHMAN Group
N=463 Warfarin Group N=244
34% lower
Rate per 100 patient years
10 PS = 0.96
P=0,0379
7,5 4,8
5 2,5
3,8 2,3
1,5
2,4
2,2
3,2
1
0 Primary Efficacy
All Stroke
Ps = Posterior Probability for Superiority
CV or Unexplained Death
All-Cause Death
Reddy, et al., HRS LBCT 2013 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
WATCHMAN™ PROTECT AF & Continued Access Protocol (CAP) Implant Success
70 63 55 48 40
67 58 50
PROTECT AF EarlyPROTECT AF Late
Discon3nua3o n %
85
91
100 95 90 85 80
95
83
✓
✓
PROTECT AF Early PROTECT AF Late
CAP
88
91
CAP
With increased operator experience
✓
70
95
PROTECT AF EarlyPROTECT AF Late
CAP
45 Day Discontinuation Rate Among Implanted
100
Success %
Average Time (Minutes)
Procedure Time
The average procedure time reduced
from 67 minutes to 50 minutes Implant success improved
from 88% to 95% Discontinuation of Warfarin
improved from 83% to 95%
of patients
Reddy VY et al. Circulation. 2011;123:417-424 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
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WATCHMAN™ PROTECT AF & Continued Access Protocol (CAP)
15 11,3 7,5 3,8 0
10 5,5
PROTECT AF EarlyPROTECT AF Late
3,7
Incidence %
1,1
0,7
PROTECT AF Early PROTECT AF Late
10 6,3
5
0 CAP
3,7
0
PROTECT AF Early PROTECT AF Late
CAP
Procedure Related Stroke
5 3,8 2,5 1,3 0
Serious Pericardial Effusion Within 7 Days Incidence %
Incidence %
Procedure/Device Related Safety Adverse Event Within 7 Days
2,2 CAP
With increased operator experience ✓
Procedure related adverse events
and serious pericardial effusions
were reduced significantly
✓
Peri-procedural strokes
were eliminated
Reddy VY et al. Circulation. 2011;123:417-424 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
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Implant Success
p = 0.01
90.9%
95.1%
94.3%
Implant success defined as deployment and release of the device into the left atrial appendage
PREVAIL Implant Success
Warfarin Cessation Study
45-day
12-month
PROTECT AF
86.6%
93.2%
PREVAIL
92.2%
99.3%
No difference between new and experienced operators
Experienced Operators:
• n=26 • 96.2%
New Operators:
• n=24 • 93.2%
Holmes DR et al. Randomized Trial of LAA Occlusion. JACC. Vol. 64: 1-12 , 2014 PROTECT-AF and CAP data: Reddy, VY et al. Circulation. 2011;123:417-424. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
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WATCHMAN™ Preliminary Results
ASA Plavix Feasibility Study
Study Objective
To evaluate the safety and feasibility of the WATCHMAN™ Left Atrial Appendage Closure device for the treatment of non-valvular atrial fibrillation in patients with a contraindication to warfarin
Study Design
Multicenter, nonrandomized, feasibility study
Primary Endpoint
The primary efficacy endpoint was defined as the combined events of ischemic stroke, hemorrhagic stroke, systemic embolism, and cardiovascular/unexplained death.
Patient Population
n = 150 Mean age 72.5 ± 4 yrs. Mean CHADS2=2.8 Mean CHA2DS2-VASc=4.4
Mean Follow-Up
14.4 months
Number of Sites
4 centers (Prague, Leipzig, Regensburg, and Frankfurt)
Reddy, et al. JACC. 2013 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
WATCHMAN™ Preliminary Results
ASA Plavix Feasibility Study
5.0% 64%
WATCHMAN Implantation for contra-indicated AF warfarin patients is: • Feasible • Low, but manageable, rate of device thrombus • Decreases the rate of stroke by 77%
Reddy, et al. JACC. 2013 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
Therapie aanbevelingen ESC 2012 • • • •
Effectiviteit ascal voor stroke preventie beperkt Gebruik CHA2DS2VASc score Schat bloedingsrisico in Overweeg hartoor afsluiting • Contra-‐indicatie (N)OAC • Verhoogd bloedingsrisico bv HASBLED > 3 • Stroke onder (N)OAC • Patient voorkeur • Noodzaak langdurige triple therapie • Nierfalen (ernstig)
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Samenvattende • Thrombo-‐embolie bij atriumfibrilleren grote veroorzaker morbiditeit en mortaliteit • (N)OAC zijn effectief echter veroorzaken ook bloedingen • Hartoor afsluiting middels Watchman is een alternatieve optie naast (N)OAC om het stroke risico te verminderen zonder bloedingen te veroorzaken • Watchman heeft zich bewezen in meerdere gerandomiseerde studies voor reductie embolie vanuit linker hartoor
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Vragen? DRES
