1. Kenneth Stein, MD FACC FHRS
Lessons From WATCHMAN Launch: FDA, CMS, and the Launch of a New Therapy
Kenneth Stein, MD FACC FHRS
Senior Vice President and Chief Medical Officer, Rhythm Management and Global Health Policy
Boston Scientific

2. Dr. Stein is a Boston Scientific employee and shareholder.
Disclosure
This presentation may include products and/or uses that have not been approved or cleared by the U.S. Food and Drug Administration and are not available for sale in the U.S.
All future product approval and launch dates are based on estimates of completion of regulatory submissions, review and/or approval or clearance, as well as other business considerations.
Dr. Stein is a Boston Scientific employee and shareholder.

3. Procedural Success1-2 ~50% new operators ~70% new operators N=449
Implant success defined as deployment and release of the device into the LAA; no leak ≥ 5 mm
N=3822
1 WATCHMAN FDA Panel Sponsor Presentation. Oct 2014; 2 Boersma, L.et al. EHJ; published online Jan 2016 in press; 3

4. Outcomes in the Post-FDA Approval Watchman Experience
 Complications 
Post-FDA Approval Experience
Pericardial Tamponade
39 (1.02%)
Treated with Pericardiocentesis
24 (0.63%)
Treated Surgically
12 (0.31%)
Resulted in Death
3 (0.078%)
Pericardial Effusion – No Intervention
11 (0.29%)
Procedure-Related Stroke
Device Embolization
9 (0.24%)
Removed Percutaneously 3
Removed Surgically 6
Death
Procedure-Related Mortality
Additional Mortality within 7 days
1 (0.026%)

5. Comparison of Procedural Complications Across Watchman Studies
AGGREGATE
CLINICAL DATA
PROCEDURAL PARAMETERS
No. of Procedures
6720
Implantation Success, %
94.9%
COMPLICATION RATES
Pericardial Tamponade
1.28%
Procedure-Related Stroke
0.18%
Device Embolization
0.25%
Procedure-Related Death
0.06%
Clinical Trial
Experience
Post Approval
Experience

6. WATCHMAN ‘NESTed’ Post Approval Study
2000 patients from the NCDR LAAO Registry
This study is ‘nested’ within the larger LAAO Registry. The data collected within this study will be collected as part of the LAAO registry. Thus, no additional data elements are required as part of the WATCHMAN NESTed study
Follow-up occurring at implant, 45 days, 6, 12 and 24 months
CMS linkage to NESTed study patients for follow-up data collection during years 2-5
1st Primary Effectiveness Endpoint*
The occurrence of stroke (including ischemic and/or hemorrhagic), cardiovascular death (cardiovascular and/or unexplained cause) and systemic embolism at 24 months.
2nd Primary Effectiveness Endpoint*
The occurrence (excluding the first 7 days post implant) of ischemic stroke or systemic embolism (thrombolic events) at 24 months.
Primary Safety Endpoint*
The occurrence of major safety events between the time of implant and within 7 days of the procedure or by hospital discharge, whichever is later
First data analysis expected Q1 2017
*Results will be compared to Performance Goals based on historical data

7. ASAP-TOO
Assessment of the WATCHMAN Device in Patients Unsuitable for Oral Anticoagulation
Indication expansion IDE study testing the safety and effectiveness of WATCHMAN in subjects unsuitable for oral anticoagulation
888 subjects at 100 global sites (65 US, 35 Intl)
Randomized 2 Device to 1 Control
Control group: Single antiplatelet or no therapy
Device group: WATCHMAN plus 3-months DAPT, followed by 9-months low dose ASA
Primary effectiveness endpoint: ischemic stroke/systemic embolism
5-year follow up
PIs: Vivek Reddy, Maurice Buchbinder, Jacqueline Saw
Current status: currently enrolling
Clinicaltrials.gov Identifier: NCT

8. The WIN-Her™ Initiative Program Summary
Patient & physician materials  barriers to female enrollment
WIN-Her Initiative Pilot success  % female enrollment
WIN-Her Initiative Data  future protocol design

9. LEIO-AF Pre-Clinical Objective: Methods: Results:
Evaluate safety and feasibility
of LAAC after electrical isolation
in canine model
Methods:
9 canine underwent PVI and LAA electrical isolation and LAAC with WATCHMAN
Results:
All PVs and 8/9 LAAs electrically isolated
Acute LAA reconnection in 4 of 8 LAAs
45-Days 7of 8 had persistent LAA electrical isolation
Heart Rhythm Jan;12(1):

10. LEIO-AF Human Feasibility
48 Screened
25 Excluded Pre-Enrollment
23 didn’t meet eligibility criteria
2 declined participation
23 Enrolled
1 Excluded Post-Enrollment
LAA ostium >33mm on baseline CT
22 catheter ablation + LAAC
20/22 successful LAA isolation
20/20* successful LAAC
2 excluded as unable to achieve pre-specified LAA electrical isolation
Follow-up analyzed (n=20)
*2 unsuccessful LAA electrical isolation therefore LAAC not attempted

11. LEIO-AF Human Feasibility: Kaplan Meier

12. LEIO:AF Study Assumptions
10 Investigational Sites
Located in the ~3 countries in EU
Have a RhythmiaTM System
Sample Size: ~ 214 subjects
Utilize WATCHMANTM FLX* Device
Randomization:
Control Group: Conventional Persistent AF Ablation
Treatment Group: Conventional Persistent AF, LAA Electrical Isolation, WATCHMAN Implant
Visits at Baseline, 6-wk, 3-, 6-, 12- and 24-months
Primary Endpoint Evaluation at 12-months
*Caution: Investigational Device. Limited by Federal (or US) law to investigational use only. Not available for sale.
CE Mark pending – not available for sale in the European Economic Area (EEA).

13. LEIO-AF: Endpoints Primary Efficacy Primary Safety Secondary
Freedom from AF/AT at 12 months
Primary Efficacy
Major procedure/device events
Stroke, Major bleeding, Death
Primary Safety
Freedom from AF at 12 months
Change in AF burden
Serious adverse cardiovascular event
Change in AF symptom score (AF-EQT and EQ-5D health score)
Cost effectiveness
Secondary

14. ABBREVIATED STATEMENT (US) WATCHMANTM Left Atrial Appendage Closure Device with Delivery System and WATCHMAN Access System
Indications for use
The WATCHMAN Device is indicated to reduce the risk of thromboembolism from the left atrial appendage 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 by their physicians 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.
The WATCHMAN Access System is intended to provide vascular and transseptal access for all WATCHMAN Left Atrial Appendage Closure Devices with Delivery Systems.
Contraindications
Do not use the WATCHMAN Device if:
Intracardiac thrombus is visualized by echocardiographic imaging.
An atrial septal defect repair or closure device or a patent foramen ovale repair or closure device is present.
The LAA anatomy will not accommodate a device. See Table 46 in the DFU.
Any of the customary contraindications for other percutaneous catheterization procedures (e.g., patient size too small to accommodate TEE probe or required catheters) or conditions (e.g., active infection, bleeding disorder) are present.
There are contraindications to the use of warfarin, aspirin, or clopidogrel.
The patient has a known hypersensitivity to any portion of the device material or the individual components (see Device Description section) such that the use of the WATCHMAN Device is contraindicated.
Warnings
Device selection should be based on accurate LAA measurements obtained using fluoro and ultrasound guidance (TEE recommended) in multiple angles (e.g., 0º, 45º, 90º, 135º).
Do not release the WATCHMAN Device from the core wire if the device does not meet all release criteria.
If thrombus is observed on the device, warfarin therapy is recommended until resolution of thrombus is demonstrated by TEE.
The potential for device embolization exists with cardioversion <30 days following device implantation. Verify device position post-cardioversion during this period.
Administer appropriate endocarditis prophylaxis for 6 months following device implantation. The decision to continue endocarditis prophylaxis beyond 6 months is at physician discretion.
For single use only. Do not reuse, reprocess, or resterilize.
Precautions
The safety and effectiveness (and benefit-risk profile) of the WATCHMAN Device has not been established in patients for whom long-term anticoagulation is determined to be contraindicated.
The LAA is a thin-walled structure. Use caution when accessing the LAA and deploying the device.
Use caution when introducing the WATCHMAN Access System to prevent damage to cardiac structures.
Use caution when introducing the Delivery System to prevent damage to cardiac structures.
To prevent damage to the Delivery Catheter or device, do not allow the WATCHMAN Device to protrude beyond the distal tip of the Delivery Catheter when inserting the Delivery System into the Access Sheath.
If using a power injector, the maximum pressure should not exceed 100 psi.
In view of the concerns that were raised by the RE-ALIGN1 study of dabigatran in the presence of prosthetic mechanical heart valves, caution should be used when prescribing oral anticoagulants other than warfarin in patients treated with the WATCHMAN Device. The WATCHMAN Device has only been evaluated with the use of warfarin post-device implantation.
ADVERSE EVENTS
Potential adverse events (in alphabetical order) which may be associated with the use of a left atrial appendage closure device or implantation procedure include but are not limited to:
Air embolism, Airway trauma, Allergic reaction to contrast media/medications or device materials, Altered mental status, Anemia requiring transfusion, Anesthesia risks, Angina, Anoxic encephalopathy, Arrhythmias, Atrial septal defect , AV fistula , Bruising, hematoma or seroma, Cardiac perforation , Chest pain/discomfort, Confusion post procedure, Congestive heart failure, Contrast related nephropathy, Cranial bleed, Decreased hemoglobin, Deep vein thrombosis, Death, Device embolism, Device fracture, Device thrombosis, Edema, Excessive bleeding, Fever, Groin pain, Groin puncture bleed, Hematuria, Hemoptysis, Hypotension, Hypoxia, Improper wound healing, Inability to reposition, recapture, or retrieve the device, Infection / pneumonia, Interatrial septum thrombus, Intratracheal bleeding, Major bleeding requiring transfusion, Misplacement of the device / improper seal of the appendage / movement of device from appendage wall, Myocardia erosion, Nausea, Oral bleeding, Pericardial effusion / tamponade, Pleural effusion, Prolonged bleeding from a laceration, Pseudoaneurysm, Pulmonary edema, Renal failure, Respiratory insufficiency / failure, Surgical removal of the device, Stroke – Ischemic , Stroke – Hemorrhagic, Systemic embolism, TEE complications (throat pain, bleeding, esophageal trauma), Thrombocytopenia, Thrombosis, Transient ischemic attack (TIA), Valvular damage, Vasovagal reactions
There may be other potential adverse events that are unforeseen at this time.   
CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician. Rx only. Prior to use, please see the complete “Directions for Use” for more information on Indications, Contraindications, Warnings, Precautions, Adverse Events, and Operator’s Instructions.
© 2015 Boston Scientific Corporation or its affiliates. All rights reserved. 
1Eikelboom JW, Connolly SJ, Brueckmann M, et al. N Engl J Med 2013;369: