1. LAA Closure: Lessons from the Pivotal Studies & Three Advisory Panels
Keith Dawkins MD FRCP FACC FSCAI
Global Chief Medical Officer
Executive Vice President
Boston Scientific Corporation

2. Conflict of Interest
Boston Scientific Corporation
Employee
Stockholder

3. Global Burden of Atrial Fibrillation
Individuals with AF = 33.5 million
Incidence ↑
Prevalence ↑
Disease Burden ↑
AF-Related Mortality ↑
Chugh SS: Circ 2014;129:

4. AF associated Mortality
Age-Adjusted Mortality
(per 100,000 Population)
Year
Chugh SS: Circ 2014;129:

5. Atrial Fibrillation & Anticoagulation
Atrial Fibrillation is the most common sustained cardiac arrhythmia
Fivefold increase in stroke when AF is present
INR levels outside the therapeutic range ( ) occurs in ~50% of patients
According to HAS-BLED, 61% of pts currently on Warfarin for AF are at moderate risk of bleeding and an additional 19% are at high risk
Risk of Thromboembolism in AF vs. Risk of Bleeding with Anticoagulants
Camm AJ: Euro Heart J 2010;31:
Pisters R: Chest 2010;138:

6. Warfarin Use in General Practice Initiation of Warfarin
41,000 chronic AF treated by GPs in the UK
Administrative database Study
Diagnosed after Jan 2000
Percent (%)
Years after diagnosis 2 4 6 20 40 60 80
100
Age 40 – 64
Age 85 +
Age 80 – 84
Age 75 – 79
Age 70 – 74
Age 65 – 69
Gallagher AM: J Thromb Haemost. 2008;6:

7. Why do Physicians Underuse Warfarin in AF?
Most Cited Reasons:
Bleeding Risk
Advanced Age
Other factors influencing prescriptions:
Previous Falls
Perceived Fall Risk
Comorbidities (cognitive impairment, alcohol)
Inability to comply with monitoring/treatment
Pugh D: Age and Ageing 2011;40:

8. Atrial Fibrillation & Anticoagulation
High Prevalence
High Cost
Low Medication Adherence
Poor Monitoring Behavior
Poor Patient Understanding
Kneeland PP: Patient Prefer Adherence 2010;4:51-60

9. The Watchman™ Device Features 160μm membrane Nitinol Frame in 5 Sizes
Delivered via 14Fr catheter
Repositionable and retrievable
Average procedure takes minutes
160μm membrane
Polyethyl Terephthalate (PET) cap designed to block emboli and promote healing at 45 days
Nitinol Frame in 5 Sizes
Radially expands to maintain position in the LAA
10 Active Fixation Anchors
Designed to maintain position within the LAA

10. LAAC Prevents Propagation of Left Atrial Thrombosis in AF

11. Watchman™ Device ImplantLV
Watchman Device

12. The Watchman™ Journey…
CE-Mark
1st FDA
Panel
BSC Acquires
Atritech
2nd FDA
Panel
3rd FDA
Panel ?
Approval
PROTECT AF Trial
Enrollment
PREVAIL Trial
Enrollment
Watchman™ has been commercialized in 77 Countries

13. Watchman™ Clinical Program
Pilot
Early feasibility with >6 years of follow-up
n=66
PROTECT-AF
Watchman™ primary efficacy, CV death, and hemorrhagic stroke superior to warfarin at 5 years
n=800
CAP Registry
Significantly improved safety results
n=566
ASAP
Expected rate of stroke reduced by 77% in patients contraindicated to warfarin
n=150
Positive #3 FDA Panel October 8, 2014
PREVAIL
Improved implant success procedure safety confirmed with new and experienced operators
n=461
CAP2
Continued improvement in implant success and procedure safety.
n=579
EWOLUTION
Currently enrolling 1000 patients, 50 sites, 16 countries
n=633
WASP
Currently enrolling 300 patients, 6 Asia-Pacific countries
n=108
Over 3300 patients with >6000 patient-years of follow-up

14. Watchman™ Favorable Procedural Safety Profile
Patients with Safety Event (%)
PROTECT AF
(N=232) (N=231)
1st Half nd Half
CAP
(N=566)
PREVAIL
(N=269)
CAP2
(N=579)
All Device and/or procedure-related serious adverse events within 7 Days

15. Watchman™ Peer-Reviewed Publications

16. Left Atrial Appendage Closure
ESC Guidelines (2012)
2005
Recommendations
Class
Level
Interventional, percutaneous
LAA closure may be considered in patients with a high stroke risk and contraindications for long-term oral anticoagulation
IIb B
Eur Heart J 2012:33;2719–2747

17. Watchman™ Therapy…
Is not designed to be a broad replacement for oral anticoagulation
Is intended for patients:
At an increased risk of stroke and systemic embolism
Recommended and deemed suitable candidates for warfarin
Having an appropriate rationale to seek a non-pharmacologic alternative to warfarin 

18. Conclusions
Eight clinical trials including 3,000 patients and >6,000 patient-years of data support Watchman™ use for the Primary Endpoint (All-Cause Stroke, Systemic Embolism, Cardiovascular death), with superiority for Cardiovascular Mortality, Hemorrhagic Stroke, and Disabling Stroke (post hoc analysis)
We seek Watchman™ labeling related to the clinical trial population – i.e. patients with non-valvular atrial fibrillation at high risk based on CHADS2 or CHA2DS2-VASc scores, who are suitable for Warfarin, and who have an appropriate rationale to seek an invasive and experimental non-pharma alternative to Warfarin
Patients doing well on oral anticoagulants should continue on anticoagulants….