1. Protecting Against Stroke
LAA Closure Devices:
Protecting Against Stroke
Title Slide Layout
Moderator
Ted E. Feldman, MD
Director
Cardiac Catheterization Laboratory Evanston Hospital
Evanston, Illinois

2. Saibal Kar, MD Mark Reisman, MD Vivek Y. Reddy, MD Panelists Director
Interventional Cardiac Research
Cardiology Division
Department of Medicine
Cedars-Sinai Medical Center
Los Angeles, California
Mark Reisman, MD
Chief Scientific Officer
Director
Cardiovascular Research and Education
Swedish Medical Center
Seattle, Washington
Vivek Y. Reddy, MD
Professor of Medicine
Department of Cardiology
Icahn School of Medicine at Mount Sinai
Director
Electrophysiology Laboratories
Mount Sinai Hospital
New York, New York
Title Slide Layout

3. Placing LLA Closure Device
Insert video
Content Slide Layout: TEXT

4. Atrial 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: [2]

5. Oral 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: [3]

6. LAA: source of 90% of AF-related thrombia
Left Atrial Appendage
Left atrium
LAA: source of 90% of AF-related thrombia
a. Blackshear JL, et al. Ann Thorac Surg. 1996;61: [5]
Patrick J. Lynch, medical illustrator; C. Carl Jaffe, MD, cardiologist. 

7. Control subject takes warfarin Device subject gets implant
PROTECT 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 45
post-implant
Day 2-14
Device
Control
Fountain RB, et al. Am Heart J. 2006;151: [6]

8. Permeab Polyester fabric
WATCHMAN™ Device
Nitinol frame
Permeab Polyester fabric
Fixation barbs
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.

9. 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
Rate Ratio
(Intervention/ Control)
Noninferiority Posterior Probabilities
Superiority Posterior Probabilities
Primary Efficacy
3.0
( )
4.3
( )
0.71
( )
> 0.99
0.88
Ischemic Stroke
1.9
( )
1.4
( )
1.30
( )
0.76
0.18
CV/ Unexplained Death
1.0
( )
2.8
( )
0.38
( )
0.99 SE
0.3
( ) __
Study limitations: Small number of patients, 1/3 of patients randomized to continued warfarin, primary composite endpoint included ischemic + hemorrhagic stroke
Reddy VY, et al. Circulation. 2013;127: [7]

10. PROTECT AF 2.3-Year Follow-up Safety Results
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
Safety Events %/Year
(95% CI)
RR (95% CI)
WATCHMAN Group
5.5 ( )
Control
3.6 ( )
1.53 ( )
Conclusions:
LAA closure is noninferior to OAC
LAA implicated in the pathogenesis of stroke in AF
Reddy VY, et al. Circulation. 2013;127: [7]

11. PROTECT AF and CAP PROTECT AF CAP Patients, %
Implant Success
Patients, %
Reddy VY, et al. Circulation. 2011; 123: [8]

12. PREVAIL Study 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

13. PREVAIL Primary 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.

14. Comparison of Cardiac Perforations and Pericardial Effusions Requiring Intervention
Data courtesy of David R. Holmes, MD.

15. PREVAIL Complications
New vs Experienced Operator
Patients, %
Data courtesy of David R. Holmes, MD.

16. Using 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)

17. Thank you for participating in this activity.
To proceed to the online CME test, click on the Earn CME Credit link on this page.