1. Update on the Watchman Device CRT 2010 Washington, DC
David R. Holmes, MD Mayo Clinic Rochester, MN

2. Presenter Disclosure Information
David R. Holmes, Jr., M.D.
“Update on the Watchman Device”
The following relationships exist related to this presentation: "Both Mayo Clinic and I have a financial interest in technology related to this research.  That technology has been licensed to Atritech, and Mayo Clinic and I have contractual rights to receive future royalties from this license.  To date, no royalties have been received by either Mayo Clinic or me."

3. WATCHMAN Device
WATCHMAN device and WATCHMAN ‘shorty’

5. Left Atrial Appendage Closure Devices A Perspective
Can the LAA be occluded reliably and safely?
Does LAA occlusion work?
Does potential benefit depend on CHADS2 score?
What about patients who cannot take anticoagulants?

6. PROTECT-AF Clinical Trial
Prospective, randomized study of WATCHMAN LAA Device vs Long-Term Warfarin Therapy
2:1 allocation ratio device to control
Non-inferiority study
Bayesian sequential design
Analysis at 600 pt-yr and every 150 pt-yr after

7. PROTECT-AF Trial Endpoints
Primary efficacy endpoint
All stroke: ischemic or hemorrhagic
Deficit with symptoms persisting >24 hr or symptoms <24 hr confirmed by CT/MRI
Cardiovascular or unexplained death: includes sudden death, MI, CVA, cardiac arrhythmia and heart failure
Systemic embolism
Primary safety endpoint

8. Patient Risk Factors Baseline Risk Factors
WATCHMAN n=463
Control n=244
Characteristic P
CHADS2 score
1 157/ % 66/ %
2 158/ % 88/ %
3 88/ % 51/ %
4 37/ % 24/ %
5 19/ % 10/ %
/ % 5/ %
AF pattern
Paroxysmal 200/ % 99/ %
Persistent 97/ % 50/ %
Permanent 160/ % 93/ %
Unknown 6/ % 2/ %
LVEF (%) 57.3± , ± ,

9. Risk/Benefit Analysis
Intent-to-treat analysis
Primary endpoint (intent to treat) achieved
Other statistically significant endpoint findings
Noninferiority for the primary efficacy event rate – 32% lower in device group
Noninferiority for stroke rate – 26% lower in device group
Superiority for hemorrhagic stroke – 91% lower in device group
Noninferiority for mortality rate – 39% lower rate in device group
Increased rate of primary safety events for the device group relative to the control group
Most events in the device group were procedural effusions that decreased over the course of the study
87% of patients discontinued warfarin at 45 days

10. Conclusion
The WATCHMAN LAA Technology offers a safe and effective alternative to warfarin in patients with non-valvular atrial fibrillation at risk for stroke and who are eligible for warfarin therapy

11. New medicines and new methods of cure always work miracles for awhile
William Heberden

12. Average Follow-up
Months
Patient Years

13. Primary Efficacy Endpoint
Control
Probability of event
Intervention
RR 0.62 (95% CI )
Time since randomization (days)
No. at risk
Control
Intervention

14. Primary Efficacy (Intent-to-Treat) 1350 Patient Years
WATCHMAN n=463
Control N=244
Rate Rate Rel risk (events/pt-yr) (event/pt-yr) (95% CI)
/ /
(95% CI ) (95% CI )
These rates yielded a relative risk, or rate ratio, of 0.69, a 31% lower rate of efficacy events in the WATCHMAN group than in the Control group.

15. Stroke (Intent-to-Treat) 1350 Patient Years
WATCHMAN n=463
Control N=244
Rate Rate Rel risk (events/pt-yr) (event/pt-yr) (95% CI)
/ /
(95% CI ) (95% CI )
This yielded a relative risk, or rate ratio, of 0.78, a 22% lower rate of stroke in the WATCHMAN group than in the Control group. The 95% credible interval for the rate ratio was

16. All-Cause Mortality Probability of event
Control
Probability of event
Intervention
RR 0.62 (95% CI )
Time since randomization (days)
No. at risk
Control
Intervention

17. Mortality (Intent-to-Treat) 1350 Patient Years
WATCHMAN n=463
Control N=244
Rate Rate Rel risk (events/pt-yr) (event/pt-yr) (95% CI)
/ /
(95% CI ) (95% CI )
This yielded a relative risk, or rate ratio, of 0.70, a 30% lower rate of death in the WATCHMAN group than in the Control group. The 95% credible interval for the rate ratio was

18. Intent-to-Treat: Primary Efficacy Results CHADS2 Score
WATCHMAN
Control
Cohort Events/pt-yr Event/pt-yr RR (95% CI)
All patients 21/ / ( )
CHADS / / ( )
CHADS2 >1 18/ / ( )
Composite endpoint
Stroke
CV death
Systemic embolism

19. Safety
Efficacy

20. Primary Safety (Intent-to-Treat) 1350 Patient Years
WATCHMAN n=463
Control N=244
Rate Rate Rel risk (events/pt-yr) (event/pt-yr) (95% CI)
/ /
(95% CI ) (95% CI )
The primary safety rate was 6.2 events/100 patient years for the WATCHMAN group and 3.9 events/100 patient years for the Control group

21. Safety Events Pericardial Effusion
Pericardial effusions – 47% of total device events
22 classified as “serious” (4.8% of patients)
7 required surgical intervention: extended hospitalization by 6 days
15 treated percutaneously: extended hospitalization by 4 days
None resulted in death

22. CAP Registry Patients meeting selection criteria for PROTECT AF
ALL patients treated with LAA occlusion device using the PROTECT AF protocol
379 patients
PROTECT AF n=463
CAP n=379
Periprocedural stroke
5 (1%)
Pericardial effusion
27 (5.8%)
9 (2.4%)

23. Summary of Relative Risks between Data Sets
Intent-to-Treat
600 Pt- yrs
900 Pt-yrs
1050 Pt-yrs
1200 Pt-yrs
1350 Pt-yrs
Primary Efficacy
0.76
0.68
0.62
0.70
0.69
Primary Safety
2.85
2.08
1.69
1.59
1.60
Stroke
0.96
0.74
0.71
0.80
0.78
Mortality
0.61

24. Warfarin Discontinuation
87% of implanted subjects were able to cease warfarin at 45 days and the rate further increased at later timepoints
Visit Watchman
No. %
45 day 349/
6 month 347/
12 month 261/
24 month 95/
Reasons for remaining on warfarin therapy after 45 days
Observation of flow in the LAA (n=30)
Physician order (n=13)
Other (n=9)

25. Watchman Left Atrial Appendage Closure What Can We Learn
The hypothesis that in patients with nonvalvular atrial fibrillation that stroke results from thrombus in the LAA is correct
Benefit of LAA occlusion remains stable
>90% of patients can be taken off of warfarin without harm

26. Watchman Left Atrial Appendage Closure What Can We Learn
The left atrial appendage is fragile and the landscape is unforgiving
With changes in equipment, implant technique and improved operator experience that safety improves
The risk of device embolization is very low

27. Watchman Left Atrial Appendage Closure What Can We Learn
Risk/benefit ratio of LAA occlusion does not depend on CHADS2 score or other high risk features

28. Conclusion
The WATCHMAN LAA Technology offers a safe and effective alternative to warfarin in patients with non-valvular atrial fibrillation at risk for stroke and who are eligible for warfarin therapy