1. Occlusion: Patient Selection Are the Data Supportive?
Left Atrial Appendage
Occlusion: Patient Selection
Are the Data Supportive?
Keith Dawkins MD FRCP FACC FSCAI
Chief Medical Officer
Senior Vice President
Boston Scientific Corporation

2. Keith D. Dawkins, MD Salary: Boston Scientific Corporation
Ownership Interest (Stocks, Stock Options, or other Ownership Interest):

3. Treatment Options for Atrial Fibrillation
Ablation
Pacing
Drugs for Rate Control
Embolic Management
Intervention
Warfarin
Newer OACs
Surgical Ligation
LAA Clips
Endovascular LAA Closure

4. Atrial Fibrillation
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:

5. Atrial Fibrillation in the UK
The NHS Information Centre estimated 630,000 cases of AF in the UK, and the number is expected to increase over time
46,000 new cases are diagnosed each year
3-6% of people admitted to the hospital with an acute medical condition also had AF
Year 2010
Year 2025
Population with AF (≥ 65 years)
270,172
501,253
Iqbal MB: British Medical Journal 2005; 330:238
Go AS: JAMA 2001;285:
Atrial Fibrillation: the management of atrial fibrillation Costing Report, NICE Clinical Guideline No. 36, July 2006

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 20 40 60 80
100
Age 40 – 64
Age 85 +
Age 80 – 84
Age 75 – 79
Age 70 – 74
Age 65 – 69
Percent (%) 2 4 6
Years after diagnosis
Gallagher AM: J Thromb Haemost. 2008;6:

7. Bleeding still occurs with Newer Anticoagulants
Dabigatran vs. Warfarin in Patients with Atrial Fibrillation (RE-LY Study)
P=0.31
P=0.003
Major Bleeding Risk per year (%)
Warfarin
Dabigatran
150mgs
Dabigatran
110mgs
Connolly SJ: N Engl J Med. 2009;361:

8. We understand Warfarin; we are still learning about the newer agents…
Hohnloser SH: Circulation 2012; DOI: /CIRCULATIONAHA
Uchino K: Arch Intern Med 2012; DOI: /archinternmed
FDA. Pradaxa (dabigatran etexilate mesylate):
Safety review of post-market reports of serious bleeding events. December 7, 2011
Institute of Safe Medication Practices. ISMP Medication Safety Alert, January 12, 2012

9. No Effective Antidote for Direct Thrombin Inhibitors
Eerenberg ES: Circulation 2011:124:

10. Atritech Founded in 2000. Early commercial company
Headquarters Minneapolis MN
Acquired by BSC (January 19, 2011)
Watchman® LAA Closure Device (CE-Mark 2005)

11. Holmes DR. Lancet 2009;374:

12. PROTECT AF Trial
Prospective, randomized study of WATCHMAN® LAA Closure Device vs. Long-term warfarin therapy
2:1 allocation ratio device to control
800 patients enrolled from February 2005 to June (93 roll-in; 707 randomized)
59 enrolling centers (U.S. & Europe)
Follow-up requirements:
TEE follow-up at 45 days, 6 months and 1 year
Clinical follow-up biannually up to 5 years
INR monitoring every 2 weeks for 6 months and monthly thereafter

13. PROTECT AF Trial Results
At 1065 patient-years, the WATCHMAN® Device was non-inferior to warfarin
Rate per 100 patient-years
Ischemic
Stroke
Hemorrhagic
Stroke
Systemic
Embolism
CV or Unexplained
Death
Holmes DR: Lancet 2009;374:534–42

14. PROTECT AF Trial: Primary Efficacy Results (ITT)
Primary Composite Efficacy Endpoint
Stroke (Ischemic or Hemorrhagic)
Death (Cardiovascular or Unexplained)
Systemic Embolism
Cohort
WATCHMAN®
Control
Relative Risk
(95% CI)
Posterior Probabilities
Rate (95% CI)
Non-inferiority
Superiority
600 pt-yrs
4.4
(2.6, 6.7)
5.8
(3.0, 9.1)
0.76
(0.39, 1.67)
0.992
0.734
900 pt-yrs
3.4
(2.1, 5.2)
5.0
(2.8, 7.6)
0.68
(0.37, 1.41)
0.998
0.837
1065 pt-yrs
3.0
(1.9, 4.5)
4.9
(2.8, 7.1)
0.62
(0.35, 1.25)
>0.999
0.900
1350 pt-yrs
2.9
(2.0, 4.3)
4.2
(2.5, 6.0)
0.69
(0.42, 1.37)
0.830
1500 pt-yrs
(2.1,4.3)
4.3
(2.6, 5.9)
0.71
(0.44, 1.30)
0.846
Results are consistent over time, demonstrating a 30% reduction in primary efficacy, stroke and mortality risk
Holmes DR: Lancet 2009;374:534–42

15. Watchman® Studies STUDY PATIENTS SITES COMMENTS Pilot PROTECT AF66 8
402 patient years of follow-up
57 patients with 5+ years of follow-up
PROTECT AF
800 59
2362 patient years of follow-up
3.3 years average follow-up per patient
CAP (Continued Access Registry )
566 26
Significantly improved safety results
ASAP
150 4
Treat patients contra-indicated for warfarin
EVOLVE 69 3
Evaluate next generation WATCHMAN®
PREVAIL
317
≤50
Same endpoints as PROTECT AF
Revised inclusion/exclusion criteria
Initiated enrollment October 2010
Total Patients:
1968
Enrollment as of:

16. Improved Watchman® Procedural Outcomes with Increasing Experience
P (Implant Success) = 0.001
P (procedure Time) < 0.001
Implant Success (%)
Procedure Time (mins)
Early
(n=271)
Late
(n=271)
CAP
(n=460)
PROTECT AF
Reddy VY: Circulation 2011;123:

17. Improved Watchman® Safety with Increasing Experience
PROTECT AF Early (n=271)
PROTECT AF Late (n=271)
CAP (n=460)
P=0.006
P=0.018
Adverse Events (%)
P=0.039
Procedure/Device
AE within 7 days
Serious PE
within 7 days
Procedure
Related Stroke
Reddy VY: Circulation 2011;123:

18. Training is Key to Safe Adoption
Core Curriculum
e-Learning
Simulation
Animal Models
Proctorship
Solo Operator

19. Potential Indications LAAC
Patients unsuitable, intolerant or contraindicated for anticoagulant therapy with warfarin or newer anticoagulants (e.g. bleeding risk, poor control)
Patient choice as an alternative to anticoagulant therapy
Watchman® implant at the time of AF ablation
Watchman® implant at the time of balloon mitral valvuloplasty