Left Atrial Appendage Occlusion in the Era of Novel ......2/19/2018 1 Saibal Kar, MD, FACC, FSCAI...
Transcript of Left Atrial Appendage Occlusion in the Era of Novel ......2/19/2018 1 Saibal Kar, MD, FACC, FSCAI...
2/19/2018
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Saibal Kar, MD, FACC, FSCAI
Professor of Medicine
Director of Interventional Cardiac Research
Heart Institute, Cedars-Sinai Medical Center,
Los Angeles, CA
Left Atrial Appendage Occlusion in the Era
of Novel Anticoagulants
Disclosure Statement of Financial Interest
Saibal Kar
Affiliation/Financial Relationship
• Grant/Research Support
• Consulting Fees/Honoraria
• Other Financial Benefit
Company
• Abbott Vascular, Boston Scientific, Gore Medical, Edwards Lifesciences, Mitralign
• Abbott Vascular, Boston Scientific, Gore Medical,
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
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Left Atrial Appendage(LAA) Closure
Who
The Unmet Need
Atrial Fibrillation (AF) and Stroke
▪ 15-20% of all strokes are AF related
▪ AF results in a greater disability than non-AF related
strokes.
▪ It is important to differentiate valvular vs non-valvular AF
▪ Valvular AF = AF associated with mitral stenosis or
prosthetic heart valve
▪ The incidence of AF continues rise with age
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• In non-valvular AF, >90% of stroke-causing clots that come from the left atrium are formed in the LAA
▪ In Valvular AF stasis and clot formation can occur in any part of the left atrium 1
Connection Between NVAF-Related Stroke and
the Left Atrial Appendage
AF Creates Environment for Thrombus Formation in Left Atrium
1. Blackshear JL. Odell JA., Annals of Thoracic Surg (1996)
Prevention of stroke in patients with
non-valvular AF
• Warfarin and the new oral anticoagulant
(NOAC) agents are effective in reducing
the risk of ischemic stroke.
• Challenges of long term drug therapy
Compliance
Bleeding
Failure
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Despite NOAC Adoption and Ability to Switch NOACs,
Adherence to Anticoagulation Remains a Challenge
Martinez C, et al. Thromb Haemost. 2015 Dec 22;115(1):31-9.
Treatment
Study Drug
Discontinuation Rate
Major Bleeding
(rate/year)
Rivaroxaban1 24% 3.6%
Apixaban2 25% 2.1%
Dabigatran3
(150 mg)21% 3.3%
Edoxaban4
(60 mg / 30 mg)33 % / 34% 2.8% / 1.6%
Warfarin1-4 17 – 28% 3.1 – 3.6%
For those that remain adherent, there is an annual compounding bleeding risk
NOAC Trials
Adherence and Bleeding Issues
1Connolly, S. NEJM 2009; 361:1139-1151 – 2 yrs follow-up (Corrected) 2Patel, M. NEJM 2011; 365:883-891 – 1.9 yrs follow-up, ITT 3Granger, C NEJM 2011; 365:981-992 – 1.8 yrs follow-up, 4Giugliano, R. NEJM 2013; 369(22): 2093-2104 – 2.8 yrs follow-up.
Results from different clinical investigations are not directly comparable.
Information provided for educational purposes only
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Left Atrial Appendage(LAA) Closure
When ?
Indications for LAAC
Validated Scoring Systems to Assess Stroke Risks
3. Chest. 2010 Feb;137(2):263-72.
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Validated Scoring Systems to Assess Bleeding Risks
Chest. 2010 Nov;138(5):1093-100.
Stroke prevention in Non-valvular AFOral anticoagulants vs LAA closure
Low bleeding risk High bleeding risk
Low stroke risk
(CHA2DS2-VASc <2)
Single antiplatelet
agent
Single antiplatelet
agant or nothing
High stroke risk
(CHADS-VASc ≥ 2
NOACS or Warfarin
? LAAC
LAAC
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Left atrial appendage closure(LAAC) strategies
Watchman Device Gen II
Only FDA approved LAA closure device
For stroke prophylaxis
Amulet Device Coherex Device
( Investigational in US)
Lariat device Atriclip device
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Left Atrial Appendage(LAA) Closure
Results
The Clinical Evidence
Clinical Evidence
• Randomized studies (Watchman
device)
Two clinical trials
• Registries
• Post market registries
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Watchman LAA closure
Safety
Comparison of Procedural Parameters Across
Watchman Studies
Reddy VY, Holmes DR, et al. JACC 2016; 69(3): 253-261.
No Deaths during
clinical trial
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Watchman LAA closure
Efficacy
J Am Coll Cardiol 2017;70:2964-2975
HR
p-
value
Efficacy 0.82 0.3
All stroke or SE 0.96 0.9
Ischemic stroke or SE 1.7 0.08
Hemorrhagic stroke 0.2 0.0022
Ischemic stroke or SE >7 days 1.4 0.3
CV/unexplained death 0.59 0.03
All-cause death 0.73 0.04
Major bleed, all 0.91 0.6
Major bleeding, non procedure-related 0.48 0.0003
0.01 0.1 1 10
Favors WATCHMAN Favors warfarin
Hazard Ratio (95% CI)
Patient-Level Meta-Analysis
PROTECT AF and PREVAIL 5 years
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HR
p-
value
Efficacy 0.82 0.3
All stroke or SE 0.96 0.9
Ischemic stroke or SE 1.7 0.08
Hemorrhagic stroke 0.2 0.0022
Ischemic stroke or SE >7 days 1.4 0.3
CV/unexplained death 0.59 0.03
All-cause death 0.73 0.04
Major bleed, all 0.91 0.6
Major bleeding, non procedure-related 0.48 0.0003
0.01 0.1 1 10
Favors WATCHMAN Favors warfarin
Hazard Ratio (95% CI)
Patient-Level Meta-AnalysisWATCHMAN Comparable To Warfarin For Ischemic Stroke
Ischemic
Stroke Risk
(events per
100 pt-yrs)
PREVAIL
PROTECT AF
Untreated AFTreated with WarfarinWATCHMAN Arm
CAP2
CAP
Baseline CHA2DS2-VASc Score
EWOLUTION
WASP
ResultsWATCHMAN Comparable to Warfarin for
Ischemic Stroke
EWOLUTION: Boersma Lva et al Heart Rhythm 2017;doi-10.1016/j.hrthm.2017.05.038; WASP: Philips K, et al.Journal of Arrhythmia (in press).
1.3
1.2
1.7
2.3
1.1
1.5
0
2
4
6
8
10
1 2 3 4 5
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HR
p-
value
Efficacy 0.82 0.3
All stroke or SE 0.96 0.9
Ischemic stroke or SE 1.7 0.08
Hemorrhagic stroke 0.2 0.0022
Ischemic stroke or SE >7 days 1.4 0.3
CV/unexplained death 0.59 0.03
All-cause death 0.73 0.04
Major bleed, all 0.91 0.6
Major bleeding, non procedure-related 0.48 0.0003
0.01 0.1 1 10
Favors WATCHMAN Favors warfarin
Hazard Ratio (95% CI)
Patient-Level Meta-AnalysisWATCHMAN Superior for Hemorrhagic Stroke, CV Death,
All-Cause Death, Post-procedure Bleeding
Patient-Level Meta-Analysis
WATCHMAN Superior Reduction in Disabling
Strokes
0.00%
0.50%
1.00%
1.50%
2.00%
WATCHMAN warfarin
Disabling/Fatal Strokes Non-Disabling Strokes
Disabling Stroke defined as MRS ≥2
Two strokes in PREVAIL are excluded because the baseline MRS score was unavailable
HR 0.45 (0.21 – 0.94)
P=0.03
55%
Reduction
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PROTECT and PREVAIL 5 year follow up
All-Cause Death
Reddy V, Doshi S, Kar S et al. J Am Coll Cardiol 2017;70:2964-2975
P=0.04
Summary: 5 year follow up
Long term 5-year outcomes of 2 RCTs demonstrate
• LAAC with the Watchman device provides stroke
prevention in NVAF patients to a similar degree
as oral anticoagulation
• By minimizing major bleeding, particularly
hemorrhagic stroke, LAAC results in less
disability or death than warfarin
Reddy V, Doshi S, Kar S et al. J Am Coll Cardiol 2017;70:2964-2975
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Cost effectiveness
LAAC versus NOAC versus coumadin
Warfarin vs NOACs vs LAAC:
Cummulative cost and Time to Cost-Effectiveness
QALY = Quality-adjusted life year
Reddy, V.Y. et al. J Am Coll Cardiol 2015;66:2728-39
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The WATCHMAN Device is indicated to reduce the risk of thromboembolism
from the LAA in patients with non-valvular atrial fibrillation who:
– Are at increased risk for stroke and systemic embolism based on
CHADS2 or CHA2DS2-VASc scores and are recommended for
anticoagulation therapy;
– Are deemed to be suitable for warfarin; and
– Have an appropriate rationale to seek a non-pharmacologic alternative
to warfarin, taking into account the safety and effectiveness of the
device compared to warfarin
WATCHMAN™ FDA Indications for Use
March 2015
Conclusions• Thrombus arising from the Left atrial appendage is
important cause of ischemic stroke in non-valvular AF
• Left atrial appendage closure (LAAC) is a safe and
effective alternative to coumadin for the prevention of
stroke
• LAAC is a cost effective over NOACs in the long
term.
• Further modifications of the device/therapy will
hopefully make LAAC a front line therapy in patients
with atrial fibrillation
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Who is the ideal patient with non-valvular
AF for LAA closure: be a good clinician
Ideal for patients who
• Cannot not
• Should not
• Will not
Take long term anticoagulants