LAA Closure Devices:LAA Closure Devices:Protecting Against Stroke

ModeratorTed E. Feldman, MDDirectorCardiac Catheterization Laboratory Evanston HospitalEvanston, Illinois

Panelists Saibal Kar, MDDirectorInterventional Cardiac Research Cardiology Division Department of MedicineCedars-Sinai Medical CenterLos Angeles, California

Vivek Y. Reddy, MDProfessor of MedicineDepartment of CardiologyIcahn School of Medicine at Mount SinaiDirectorElectrophysiology LaboratoriesMount Sinai Hospital New York, New York

Mark Reisman, MDChief Scientific OfficerDirectorCardiovascular Research and Education Swedish Medical CenterSeattle, Washington

Placing LLA Closure DevicePlacing LLA Closure Device

Insert video

Atrial FibrillationAtrial Fibrillation

• Stroke is a leading cause of serious, long-term disability and is the third leading cause of death in the United States.a

• AF increases stroke risk 5-fold and accounts for approximately 15% of all strokes.b

• AF affects 12% of adults ≥ 75 years and prevalence is expected to double by 2050.b

• Ischemic stroke may be the first manifestation of AF.

• Standard of care for higher risk patients: Anticoagulation with warfarin, dabigatran, rivaroxaban, apixaban

a. Rosamund W, et al. Circulation. 2008;117:e25-e146.[1]

b. Lloyd-Jones DM, et al. Circulation. 2004;110:1042-1046.[2]

Oral AnticoagulationOral Anticoagulation

• Warfarin reduces annual risk of ischemic stroke by approximately two-thirds, from 4.5% to 1.4%.a

• Risk factors for bleeding similar to risk factors for stroke• Elderly population has increased risk for falls• Interactions between warfarin and other medications, food• Many patients with AF not treated or discontinue treatment

prematurely• Novel oral anticoagulants do not require monitoring and

have few drug-drug and drug-food interactions, but also have risk for bleeding and discontinuation rate similar to warfarin

a. Go AS, et al. JAMA. 2001;285:2370-2375.[3]

Left Atrial AppendageLeft Atrial Appendage

Left atrium

a. Blackshear JL, et al. Ann Thorac Surg. 1996;61:755-759.[5]

Patrick J. Lynch, medical illustrator; C. Carl Jaffe, MD, cardiologist. http://creativecommons.org/licenses/by/2.5/

LAA: source of 90% of AF-related

thrombia

PROTECT AF DesignPROTECT AF Design

Warfarin to 45 days, then clopidogrel + aspirin to 6

months and aspirin indefinitely

Pre-implant interval

Day 0

Control subject takes warfarin

Device subject gets implant

Warfarin ceased

Ongoing to 5 years

Randomize

Day 0Day 45

post-implantDay 2-14 Ongoing to 5 years

Dev

ice

Co

ntr

ol

Fountain RB, et al. Am Heart J. 2006;151:956-961.[6]

The WATCHMAN LAA closure technology has CE Mark approval and is currently available for investigational use only in the United States. Image courtesy of Boston Scientific Corp.

WATCHMAN™ DeviceWATCHMAN™ Device

Nitinol frame

Permeab Polyester fabric

Fixation barbs

PROTECT AF 2.3-Year Follow-up Efficacy Results

Device No. of

Events/100 Patient-

year(95% Crl)

Control No. of

Events/ 100 Patient-

year(95% Crl)

Rate Ratio(Intervention/

Control)(95% Crl)

Noninferiority Posterior

Probabilities

Superiority Posterior

Probabilities

Primary Efficacy

3.0(2.1-4.3)

4.3(2.6-5.9)

0.71(0.44-1.30)

> 0.99 0.88

Ischemic Stroke

1.9

(1.1-2.9)

1.4

(0.6-2.4)

1.30

(0.66-3.66)0.76 0.18

CV/ Unexplained Death

1.0

(0.5-1.8)

2.8

(1.5-4.2)

0.38

(0.18-0.85)> 0.99 0.99

SE0.3

(0.1-0.7)0 __ __ __

Reddy VY, et al. Circulation. 2013;127:720-729.[7]

Study limitations: Small number of patients, 1/3 of patients randomized to continued warfarin, primary composite endpoint included ischemic + hemorrhagic stroke

PROTECT AF 2.3-Year Follow-up Safety ResultsPROTECT AF 2.3-Year Follow-up Safety Results

Safety Events %/Year(95% CI) RR (95% CI)

WATCHMAN Group

5.5 (4.2-7.1)

Control 3.6 (2.2-5.3) 1.53 (0.95-2.70)

Reddy VY, et al. Circulation. 2013;127:720-729.[7]

• Procedure-related events – eg, pericardial effusion that required intervention or hospitalization,

procedure-related stroke, or device embolization • Major bleeding

– eg, intracranial bleeding/GI bleeding that required transfusion

Conclusions: • LAA closure is noninferior to OAC• LAA implicated in the pathogenesis of stroke in AF

PROTECT AF and CAPPROTECT AF and CAP

Reddy VY, et al. Circulation. 2011; 123:417-424.[8]

Procedure/Device-Re-lated ADE < 7 days

Serious Pericardial Ef-fusion

Procedure/Device-Re-lated Stroke

0

1

2

3

4

5

6

7

8

9

7.7

5

0.9

3.7

2.2

00

10

20

30

40

50

60

70

80

90

100

89.595

Implant Success

Pat

ien

ts, %

PROTECT AF

CAP

PREVAILStudy GoalsPREVAILStudy Goals

• Multicenter, prospective, randomized 2:1 trial

• 407 patients, 41 US centers

• Confirm the results of PROTECT AF and demonstrate improved safety profile

• New centers and operators to document that enhancements to the training program are effective

• Roll-in phase allowed new centers to implant 2 patients prior to randomization phase

PREVAILPrimary EndpointsPREVAILPrimary Endpoints

• First Primary Endpoint

– Acute (7-day) Procedural Safety : Pre-specified criterion met

(95% Upper confidence bound < 2.67%); 95% CI = 2.618%

• Second Primary Endpoint

– Comparison of composite of stroke, SE, and

CV/unexplained death: Similar 18-month event

rates in both control and device groups

Data courtesy of David R. Holmes, MD.

Comparison of Cardiac Perforations and Pericardial Effusions Requiring Intervention

Comparison of Cardiac Perforations and Pericardial Effusions Requiring Intervention

0.00.51.01.52.02.53.0

1.6

2.4

0.2

1.21.4 1.5

PROTECT AF CAP PREVAIL

Patie

nts,

%

n = 7 n = 1n = 1 n = 11 n = 7 n = 4

Data courtesy of David R. Holmes, MD.

Device Embolization0.0

0.5

1.0

1.5

2.0

1.2

0

Pa

tie

nts

, %

7-Day Procedure-/Device-Related Vas...0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

5.4

2.9

Experienced New

Cardiac Perforation0.0

0.2

0.4

0.6

0.8

1.0

0.6

0

Pa

tie

nts

, %

n = 1

PE with Tamponade0.0

0.5

1.0

1.5

2.0

2.5

3.0

1.8%

1.0%

Pa

tie

nts

, %

n = 3

PREVAIL Complications New vs Experienced Operator

Pat

ien

ts,

%

Data courtesy of David R. Holmes, MD.

Using LAA DevicesUsing LAA Devices

• Expertise with TEE imaging of LAA

– Close working relationship with EPs

• Development of program/system for use of devices

– Training programs

• Barriers to using devices vs medical therapy

– Fear of procedure complications

• Many new devices under investigation:• Amplatzer™ Vascular Plug (St. Jude Medical), Lariat® Suture

Delivery Device (SentreHEART, Inc.), WaveCrest ® LAA Occlusion System (Coherex)

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