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

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

Placing LLA Closure Device Insert video Content Slide Layout: TEXT

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;110:1042-1046.[2]

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;285:2370-2375.[3]

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;61:755-759.[5] Patrick J. Lynch, medical illustrator; C. Carl Jaffe, MD, cardiologist.  http://creativecommons.org/licenses/by/2.5/

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;151:956-961.[6]

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.

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 (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 SE 0.3 (0.1-0.7) __ 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;127:720-729.[7]

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 (4.2-7.1) Control 3.6 (2.2-5.3) 1.53 (0.95-2.70) Conclusions: LAA closure is noninferior to OAC LAA implicated in the pathogenesis of stroke in AF Reddy VY, et al. Circulation. 2013;127:720-729.[7]

PROTECT AF and CAP PROTECT AF CAP Patients, % Implant Success Patients, % Reddy VY, et al. Circulation. 2011; 123:417-424.[8]

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

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.

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

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

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)

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