Left Atrial Appendage Occlusion in the Era of Novel ... · 2/19/2018 2 Left Atrial Appendage(LAA) Closure Who The Unmet Need Atrial Fibrillation (AF) and Stroke 15-20% of all strokes

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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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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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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









0.01 0.1 1 10



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









0.01 0.1 1 10



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

Documents

Left Atrial Appendage Occlusion in the Era of Novel ... · 2/19/2018 2 Left Atrial Appendage(LAA) Closure Who The Unmet Need Atrial Fibrillation (AF) and Stroke 15-20% of all strokes