1. A Viable Option for Stroke Risk Reduction
WATCHMAN™
A Viable Option for Stroke Risk Reduction
Clinical Data Overview

2. Agenda Need for a Device-Based Alternative for Stroke Risk Reduction
WATCHMAN Clinical data
Clinical Study Overview: The Most Studied LAAC Device
Efficacy – Stroke Risk Reduction
Efficacy – Bleeding Reduction, Warfarin Cessation & Mortality Reduction
Procedural Success & Safety
Real World & Expanded Patient Populations

3. WATCHMAN Clinical Data
Need for a Device-Based Alternative for Stroke Risk Reduction

4. Atrial Fibrillation: An Independent Risk Factor for Stroke6M
12M 5X
~2X
1 in 6 strokes occur in patients with AF3
increased risk of stroke for AF patients2
greater likelihood of stroke recurrence in AF patients (within 6 months)4
~6M
people with AF in U.S., expected to more than double by 20301
1Benjamin EJ. et al, Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association. Circulation. 2018; 137: e67-e492.
2Holmes DR, Atrial Fibrillation and Stroke Management: Present and Future, Seminars in Neurology 2010;30:528–536
3Hart RG, Halperin JL. Atrial fibrillation and thromboembolism: a decade of progress in stroke prevention. Ann Intern Med. 1999.
4Wolf PA et al, Duration of Atrial Fibrillation and the Imminence of Stroke: The Framingham Study, Stroke 1983; 14:

5. AF Creates Environment for Thrombus Formation in the Left Atrium
Stasis-related LA thrombus is a predictor of TIA1 and ischemic stroke2. In non-valvular AF, > 90% of stroke-causing clots that come from the left atrium are formed in the LAA3
1Stoddard et al. Am Heart J. 2003; 145(4): Goldman et al. J Am Soc Echocardiography. 1999: 12(12): Blackshear JL., Odell JA. Annals of Thoracic Surg. 1996; 61:

6. AF-Related Strokes are Debilitating#1
cause of adult disability worldwide1
1.5X
Stroke
AF-related Stroke
higher disability3** 2X
higher mortality3**
70%
result in death or permanent disability6
Cognitive Deficits*
Aphasia*
Unable to Walk Unassisted*
Bladder Incontinence*
Depression5
Visual Impairment*
Social Disability*
Employed Post-Stroke2
Hemiparesis*
*at 6 months post-stroke4
**compared with stroke patients without AF
1Chee and Tan. Med J Malaysia 69.3 (2014): Sreedharan et al. Journ of the neurological sciences 332.1 (2013): Lamassa et al. Stroke 32.2 (2001): Kelly-Hayes et al. Journ of Stroke and Cerebrovascular Diseases 12.3 (2003): Loo and Gan. International Journ of Stroke 7.2 (2012): Holmes DR, Seminars in Neurology 2010;30:528–536.

7. Balance stroke risk reduction benefit vs. bleeding risk
2014 ACC/AHA/HRS Treatment Guidelines to Prevent Thromboembolism in Patients with AF & 2019 Focused Update
Assess stroke risk with CHA2DS2-VASc score
Score 1 in men & 2 in women: Annual stroke risk 1%- 2%, oral anticoagulants or aspirin may be considered
Score ≥2 in men & ≥3 in women: Annual stroke risk 2%-15%, oral anticoagulants are recommended
Balance stroke risk reduction benefit vs. bleeding risk
&
CHA2DS2-VASc Score
in Men
In Women
Recommendation
No anticoagulant 1 2
Aspirin ( mg daily) or oral anticoagulants may be considered
≥ 2
≥ 3
Oral anticoagulants are recommended*
*DOACS (dabigatran, rivaroxaban, apixaban, and edoxaban) recommended over warfarin in DOAC-eligible patients
January, CT. et al AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. JACC. 2014; doi: /j.jacc
January, CT. et al AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. JACC. 2019; doi: /CIR

8. 2019 ACC/AHA/HRS Focused Update on Atrial Fibrillation
WATCHMAN included in AF Guidelines
Speaker Notes:
The ACC/AHA/HRS Guidelines were updated in 2019 to include LAAC as a Class IIb treatment for NVAF patients with contraindications to long-term anticoagulation.
While oral anticoagulation is still the preferred therapy for stroke prevention, WATCHMAN is a recommended alternative for patients who are poor candidates for long-term oral anticoagulation. Examples of patients who are poor candidates for long-term OAC include those with a propensity for bleeding and those who have poor drug tolerance or adherence.
“Oral anticoagulation remains the preferred therapy for stroke prevention for most patients with AF and elevated stroke risk. However, for patients who are poor candidates for long-term oral anticoagulation (because of the propensity for bleeding or poor drug tolerance or adherence), the Watchman device provides an alternative.”
January, CT. et al AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. JACC. 2019; doi: /CIR

9. Stroke Treatment Option: Warfarin
Warfarin is an effective means of stroke risk reduction in patients with AF, but can present challenges -5 - -4 -3 -2 -1
INR
Over-anti-coagulated
Under-anti-coagulated
Therapeutic Range
44% of bleeding events occur in patients above therapeutic range1
48% of thromboembolic events occur in patients below therapeutic range1
Many patients spend a significant amount of
time outside of the therapeutic range.
Warfarin tops the list for emergency hospitalizations
for adverse drug events in older Americans2.
1 Oake N, et al. Can Med Assoc J. 2007:176(11);1589−1594
2 Budnitz, MD, MPH. et al. Annals of Internal Medicine. 2007:147(11); 229

10. Oral Anticoagulation is Standard of Care, but Gaps in Care Remain
Despite increasing risk of stroke, the use of OAC in AF patients peaks at ~50%
Warfarin Sodium
Non-vitamin K Antagonist Oral Anticoagulant
Aspirin + Thienopyridine
Aspirin Only
No Antithrombotic Therapy
OACs
1. Hsu, J et al. JAMA Cardiol. Published online March 16, doi: /jamacardio

11. Despite Increasing Usage of DOACs, Gaps in Care Remain
Data from the NCDR PINNACLE Registry shows that the rate of overall OAC use increased from 52.4% to 60.7% with the introduction of DOACs
Still, nearly 40% of OAC-eligible patients are not receiving OAC therapy.
Marzec et al. JACC 2017: 69(20):

12. Everyday Challenges of Oral Anticoagulation
83% of patients with AF would be willing to try a different treatment to help reduce their risk of stroke1
Direct Oral Anticoagulants (DOACs)
Bleeding risk
Daily or 2x/daily regimen
High non-adherence rates
Complicates surgical procedures
High cost
Warfarin
Daily regimen
Regular INR monitoring
Food and drug interaction issues
1National Online Survey conducted by The Harris Poll of more than 400 people (aged 45 and older) living with AF.

13. Despite DOAC Adoption and Ability to Switch DOACs, Adherence to Anticoagulation Remains a Challenge
About 30% of DOAC patients discontinue treatment at 2 years
Martinez C, et al. Thromb Haemost. 2016;115(1): doi: /TH

14. Study Drug Discontinuation Rate
DOAC Trials – Adherence and Bleeding Issues
For those that remain adherent, bleeding risks persist
Treatment
Study Drug Discontinuation Rate
Major Bleeding
(rate/year)
Rivaroxaban1
24%
3.6%
Apixaban2
25%
2.1%
Dabigatran3
(150 mg)
21%
3.1%
Edoxaban4
(60 mg / 30 mg)
34% / 33%
2.8% / 1.6%
Warfarin1-4
17 – 35%
3.1 – 3.4%
Results from different clinical investigations are not directly comparable. Information provided for educational purposes only
*Rivaroxaban: 1.9 years follow-up; Apixaban: 1.8 years follow-up; Dabigatran: 2 years follow-up; Edoxaban: 2.8 years follow-up
1Patel, M. NEJM 2011; 365(10): Granger, C NEJM 2011; 365(11): Connolly, S. NEJM 2009; 361(12): , 4Giugliano, R. NEJM 2013; 369(22):

15. WATCHMAN Device Patient Selection1 2 3
Increased Risk for Stroke & Recommended for Anticoagulation
(CHA2DS2-VASc ≥ 2 in men and ≥ 3 in women)
Suitable for warfarin
Patient Has Appropriate
Rationale to Seek a Non-Pharmacologic Alternative to warfarin
Patient May Be a Candidate for the WATCHMAN LAAC Device
Yes No
US 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
Speaker Notes:
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, are deemed by their physicians to be suitable for warfarin, and have an appropriate rationale to seek a non-pharmacologic alternative to warfarin.
* Please refer to product DFU for more specific details on patient selection

16. WATCHMAN Clinical Data
Clinical Study Overview

17. WATCHMAN Clinical Timeline
More than 6,000 patients and over 15 years of experience
2002 Pilot
N=66 Non-randomized
Feasibility and Safety
2005 PROTECT AF
N=707 Randomized
Comparison: warfarin
2008 CAP Registry
N=566 Non-randomized
Add’l patients and follow-up
2009 ASAP
N=150 Non-randomized
Patients Contra-indicated to warfarin*
2010 PREVAIL
N=407 Randomized
2013 EWOLUTION, WASP Registries
N=1020, N=201 Non-randomized
Real-world, All comers
2016 US NESTed NCDR LAAO Registry
N=2000
Post-approval statistical analysis
2012 CAP2 Registry
N=579
Non-Randomized
2017 ASAP TOO
N= Up to 888
Randomized
US Indication
Expansion
Worldwide study
2017 SALUTE
N= 42
Non-randomized
Japanese Approval Study
Mar 2015
FDA Approval
2018 PINNACLE FLX
N=400
FLX Device**
US IDE
2002
2013
2018
2019 OPTION
N=1600
Comparison: OAC
*trial design in development
2017
WATCH-TAVR
N=312
Randomized
TAVR+WATCHMAN
*Not US Indication
**Caution: The WATCHMAN FLX™ is an investigational device and restricted by Federal law to investigational use only. Not available for sale in the US. CE Marked.

18. WATCHMAN Clinical Program
WATCHMAN is the most studied LAAC Device - with the most patients, and the only one with long-term clinical data
Key Trials N
Highlights
Pilot ( ) 66
Feasibility trial assessing the feasibility of implanting a device in the left atrial appendage (LAA)
PROTECT AF1 ( )
707
Prospective, randomized 2:1, non-inferiority trial of LAA closure vs. warfarin.
CAP2 ( )
566
Prospective registry allowing continued access to the WATCHMAN Device and gain further information prior to PMA approval.
ASAP3 ( )
150
Prospective registry to evaluate appendage closure in a population contraindicated to warfarin therapy
PREVAIL4 ( )
407
Prospective, randomized 2:1, non-inferiority trial to collect additional information on the WATCHMAN Device.
CAP2 ( )
579
Prospective registry allowing continued access to the WATCHMAN Device prior to PMA approval.
EWOLUTION ( )5
1020
Prospective registry allowing all patients receiving a WATCHMAN Device at participating centers in Europe, Middle East and Russia
WASP ( )
201
Prospective registry allowing all patients receiving a WATCHMAN Device at participating centers in East Asian, Australia, and Saudi Arabia
NESTed PAS (2017)
2000
Prospective registry designed to assess safety and effectiveness of the WATCHMAN Device in real world use (US only)
SALUTE (2017) 42
Prospective non-randomized trial to evaluate the safety and effectiveness of WATCHMAN in Japanese Medical Environment
ASAP-TOO (2016 -
Up to 888
Prospective randomized 2:1, superiority trial of WATCHMAN in patients not suitable for oral anti-coagulation therapy
Total patients
>6,000
>10,000 Patient-Years of Follow-up
WATCHMAN is the most studied LAAC device - most patients and only one with long-term clinical data.
Protect AF was prospective, randomized, multicenter trial with 707 patients studying the device versus warfarin.
Cap was a prospective continued access registry collecting additional data on device patients while awaiting approval
Prevail was the 2nd prospective, randomized trial versus warfarin to collect additional device data
Cap2 was another prospective continued access registry after Prevail.
Portfolio of over 6000 patients studied and over 15 years of experience.
3 positive votes from FDA sponsored panels
1. Reddy VY et al. JAMA. 2014; 312(19): Reddy VY et al. Circulation. 2011; 23: Reddy et al. JACC 2013; 61(25): 2551– Holmes et al., JACC 2014; 64(1): Boersma LVA et al. CCI (2016); 88(3): Phillips, K et al. APHRS 2017, Pacifico Yokohama. 7. Aonuma K et al. Circulation 2018; 82:

19. > 92% warfarin cessation after 45 days, > 99% after 1 year5
WATCHMAN Clinical Summary
A safe alternative to long-term warfarin therapy which offers comparable stroke risk reduction and enables patients to stop taking warfarin1,5
Demonstrated statistically superior reductions in disabling/fatal strokes, major non- procedure related bleeding and cardiovascular death compared to warfarin1,2
Demonstrated 95% implant success rate and a 1.5% major procedural complication rate with both new and experienced operators3,4
> 92% warfarin cessation after 45 days, > 99% after 1 year5
1Reddy VY, et al. JACC 2017; 70(24): Price MJ, et al. JACC: CV Interv 2015; 8(15): Reddy VY, et al. JACC 2017; 69(3): Ellenbogen KA et al. Heart Rhythm. 2019; 16(5): S310 5Holmes, DR et al. JACC 2014; 64(1): 1-12

20. WATCHMAN Clinical Data
Efficacy – Stroke Risk Reduction

21. PROTECT AF & PREVAIL 5 Year Patient Level Meta-AnalysisHR
p-value
Efficacy
0.82
0.27
All stroke or SE
0.96
0.87
Ischemic stroke or SE
1.71
0.08
Hemorrhagic stroke
0.20
<0.001
Ischemic stroke or SE >7 days
1.40
0.28
Disabling/Fatal Stroke (MRS change of ≥2)
0.45
0.03
Non-Disabling Stroke
1.37
0.35
CV/unexplained death
0.59
All-cause death
0.73
0.04
Major bleed, all
0.91
0.60
Major bleeding, non procedure-related
0.48
Favors WATCHMAN 
 Favors warfarin
Hazard Ratio (95% CI)
Reddy VY, et al. JACC 2017; 70(24):

22. WATCHMAN Comparable to Warfarin for Ischemic Stroke
Ischemic Stroke Risk (events per 100 pt-yrs)
PREVAIL
PROTECT AF
Untreated AF
Treated with Warfarin
WATCHMAN Arm
CAP2
CAP
Baseline CHA2DS2-VASc Score
EWOLUTION
WASP
ASAP
The ischemic stroke rates of non-valvuar atrial fibrillation patients who are either untreated (dotted line) or treated with warfarin (solid line) are shown as a function of the baseline CHA2DS2-VASc score using two large population databases. On this graph, the ischemic stroke rates and 95% confidence intervals of the LAAC arms from various clinical trials are shown. Because the baseline CHA2DS2-VASc scores for CAP and WASP were identical, they are arbitrarily offset for clarity; CAP2 and EWOLUTION were similarly offset for clarity. This imputed placebo analysis demonstrates the consistent performance of LAA closure with the Watchman device in preventing ischemic stroke across the various clinical studies.
CI = confidence interval; HR = hazard ratio; SE = systemic embolism; CV = cardiovascular; LAA = left atrial appendage; CAP = Continued Access to PROTECT AF registry; CAP2 = Continued Access to PREVAIL;
EWOLUTION = Registry on Watchman Outcomes in Real-Life Utilization; WASP = Registry on WATCHMAN Outcomes in Real-Life Utilization WASP Registry.
Friberg. Eur Heart J (2012); NICE UK (2014). WATCHMAN FDA Panel Sponsor Presentation. Oct 2014; Reddy VY, et al. JACC 2017; 70(24): ;
Phillips, K et al. APHRS Taipei, Taiwan; Boersma LVA ECS 2018; LBCT; Sharma D et al. JACC 2016; 67(18):

23. Disabling Stroke defined as MRS ≥2
PROTECT AF & PREVAIL Meta-Analysis (5 Year) WATCHMAN Shows Significant Reduction in Disabling Strokes
Disabling/Fatal Strokes
Non-Disabling Strokes
HR 0.45 (0.21 – 0.94)
P=0.03
55% Lower
Event Rate per 100 PY
Disabling Stroke defined as MRS ≥2
Two strokes in PREVAIL are excluded because the baseline MRS score was unavailable
Reddy VY, et al. JACC 2017; 70(24):

24. WATCHMAN Clinical Data
Efficacy – Bleeding Reduction, Warfarin Cessation & Mortality Reduction

25. Difficult to Strike a Balance in Stroke and Bleeding Risk
CHA2DS2-VASc Score
Annual % Stroke Risk 1
1.3 2
2.2 3
3.2 4
4.0 5
6.7
HAS-BLED Score
Annual % Bleed Risk
0.9 1
3.4 2
4.1 3
5.8 4
8.9 5
9.1
A patient with a CHA2DS2-VASc score of 3 is at a 3.2% annual risk of stroke. If the patient has a HAS-BLED score of 2, their annual bleeding risk is 4.1%. Their bleeding risk and stroke risk are about equal, and therefore OAC may be a good option.
However, if the same patient had a HAS-BLED score of 4, their annual bleeding risk is 8.9%. In this case, their annual bleeding risk is significantly higher than their annual risk of stroke.
Note: The HAS-BLED scoring system predicts a patient’s risk of major bleeding while on warfarin.
12014 AHA/ACC/HRS Guidelines. 2Lip. JACC ; 57(2):

26. Bleeding Risk Compounds Over Patients’ Lifetime
HAS-BLED Score
Annual % Bleed Risk (%)
10-Year Bleeding Risk (%)*
0.9
8.6 1
3.4
29.2 2
4.1
34.2 3
5.8
45.0 4
8.9
60.6 5
9.1
61.5
HAS-BLED Score
Percent Bleeding Risk (%)
Furthermore, the risk of bleeding compounds over a patients’ lifetime. This same patient with a HAS-BLED score of 4 and an annual bleeding risk of 8.9% has a 10-year bleeding risk of nearly 61%.
Note: The HAS-BLED scoring system predicts a patient’s risk of major bleeding while on warfarin.
*Assumes constant risk despite that increasing age and bleeding risk are independent from bleeding risk in previous years
The HAS-BLED scoring system predicts a patient’s risk of major bleeding while on warfarin.
Lip. JACC ; 57(2):

27. Freedom of Major Bleeding Over 3 Adjunctive Pharmacotherapy Intervals
Bleeding Outcomes after Left Atrial Appendage Closure Compared with Long-term Warfarin
Freedom of Major Bleeding Over 3 Adjunctive Pharmacotherapy Intervals
p < 0.001
72%
>6 months post-procedure
Price, MJ, et al. JACC: CV Interv 2015; 8(15): Note: This data is from 5 year results from PROTECT AF and 2 year results from PREVAIL.

28. WATCHMAN Enables Patients to Discontinue Taking Long-term OAC
92% of patients were able to discontinue warfarin after 45 days, with 99% able to discontinue after 1 year3
45 Days
1 Year
92%
99%
Warfarin Cessation with WATCHMAN
Study
45-day
12-month
PROTECT AF
87%
>93%
CAP
96%
>96%
PREVAIL
92%
>99%
CAP24
1. Reddy, VY et al. Circulation. 2011;123: WATCHMAN FDA Panel Sponsor Presentation. Oct Holmes, DR et al. JACC 2014; 64(1): Data on File

29. All-Cause Mortality PROTECT AF/PREVAIL Meta-Analysis 5-Year Results
WATCHMAN arm reported
reduced all-cause mortality by 27% compared to warfarin
(P=0.04)
Rate per 100 pt-yrs
Reddy VY, et al. JACC 2017; 70(24):

30. WATCHMAN Clinical Data
Procedural Success and Safety

31. Consistent Successful Device Deployment Across Clinical Trials and Real-World Experience
~50% new operators
~70% new operators
Procedural success across all trials and in the commercial experience is excellent!
N=449
N=566
N=265
N=579
N=1019
N=3822
N=150
N=201
Implant success defined as deployment and release of the device into the LAA; no leak ≥ 5 mm
1Boersma, L.et al. EHJ (31): Reddy VY, et al. JACC 2017; 69(3): Phillips KP et al. ILC Heart & Vasculature 2019; 23(100358)

32. Favorable Procedural Safety Profile: All Device and/or Procedure-related Serious Adverse Events within 7 Days
PROTECT AF 1st Half
PROTECT AF 2nd Half
CAP
PREVAIL
CAP2
EWOLUTION*
N=232
N=231
N=566
N=269
N=579
N=1019
Patients With Safety Event (%)
Clinical Trial Experience
Post Approval Experience
*SAE defined as all major cardiac adverse events within 7 days of implant and other device/procedure-related SAEs
Speaker Notes:
Safety event rates a low across RCTs and real world experience, with rates continuing to improve with each trial. This is Especially important because 50% of the operators in Prevail had no prior experience with LAA closure.
Beyond the first half of PREVAIL, safety event rates are comparable to other procedures performed in the LA such as AF ablation.
WASP
N=201
* The EWOLUTION and WASP Registries are prospective registries which reflects CE Mark indications for use which differ from the FDA indications for use.
1WATCHMAN FDA Panel Sponsor Presentation. Oct Boersma LVA et al. EHJ 2016; 37: Reddy VY, et al. JACC 2017; 69(3): Varosy P et al. JACC 2018; 71(11): A320. 5Phillips KP et al. ILC Heart & Vasculature 2019; 23(100358)

33. Clinical Trial Experience Post Approval Experience
Favorable Procedural Safety Profile: Major Procedural Complications Across WATCHMAN Studies
Clinical Trial Experience
Post Approval Experience
1.7%
* The EWOLUTION Registry is a European prospective registry which reflects CE Mark indications for use which differ from the FDA indications for use.
Reddy VY, et al. JACC 2017; 69(3):

34. Favorable Procedural Safety Profile: Major Procedural Complications Across WATCHMAN Studies
PROTECT-AF
PREVAIL
CAP
CAP2
EWOLUTION
Post-FDA Approval
Aggregate Data
Pericardial Tamponade
20 (4.3%)
5 (1.9%)
8 (1.4%)
11 (1.9%)
3 (0.29%)
39 (1.02%)
86 (1.28%)
Treated with pericardiocentesis
13 (2.8%)
4 (1.5%)
7 (1.2%)
n/a
2 (0.20%)
24 (0.63%)
Treated surgically
7 (1.5%)
1 (0.4%)
1 (0.2%)
1 (0.10%)
12 (0.31%)
Resulted in death
3 (0.078%)
Pericardial effusion – no intervention
4 (0.9%)
5 (0.9%)
3 (0.5%)
4 (0.39%)
11 (0.29%)
Procedure-related stroke
5 (1.15%)
1 (0.37%)
2 (0.35%)
12 (0.18%)
Device embolization
3 (0.6%)
2 (0.7%)
9 (0.24%)
17 (0.25%)
Removed percutaneously 1 3
Removed surgically 2 6
Death
Procedure-related mortality
1 (0.1%)
4 (0.06%)
Additional mortality within 7 days
1 (0.17%)
1 (0.026%)
5 (0.07%)
* The EWOLUTION Registry is a European prospective registry which reflects CE Mark indications for use which differ from the FDA indications for use.
Reddy VY, Holmes DR, et al. JACC 2017; 69(3):

35. WATCHMAN NESTed SAP: Overview
Study Objective
FDA mandated post-market surveillance analysis plan
Study Design
Prospective, newly implanted WATCHMAN device patients nested within the larger LAAO Registry (NCDR)
Primary Endpoints
1st Effectiveness
All-stroke, all-cause death, and systemic embolism at 24 months
2nd Effectiveness
Ischemic stroke or systemic embolism (thrombolic events) at 24 months, excluding the 1st 7 days post implant
Safety Endpoint
Major safety events between the time of implant and within 7 days of the procedure or by hospital discharge, whichever is later
Patient Population
2000 (2 cohorts of 1000)
Enrollment
On-going
Follow-up
45 days, 6, 12 and 24 months
CMS linkage study patients during years 2-5
Status
Follow-up on-going
Novel Evaluation of the WATCHMAN LAA Closure Therapy Surveillance Analysis Plan
This is BSC’s portion of the NCDR. This will give us important real-world safety and efficacy data. 35

36. Real World Data: NESTed SAP (LAAO Registry) Major Procedural Complications within 7 Days
Low procedural complication rate of 1.5%
in highest risk population of any study to date
17 events
P =
Performance Goal < 3.36%
Event Rate (95% CI)
Primary Safety Endpoint
Mean Age (yrs): 76.6±8.2
Mean CHADS2: 3.2 ± 1.3
Mean CHA2DS2-VASc: 5.0 ± 1.4
HAS-BLED: 2.7 ± 1.0
Primary Safety (N=1000)
1.5% (15 pts, 17 events)
Retroperitoneal bleeding
0.3% (3)
Systemic thromboembolism (other than stroke)
0.2% (2)
Surgery
0.5% (5)
Death
0.4% (4)
Pericardial effusion with surgery
0.1% (1)
Ischemic Stroke
Primary composite safety endpoint: death, ischemic stroke, systemic embolism, or device/procedure-related events necessitating cardiac surgery or major endovascular intervention within either 7-days post-implant or hospital discharge, whichever occurred later.
Ellenbogen KA et al. Heart Rhythm. 2019; 16(5): S310

37. WATCHMAN Implant Procedure
1 Day Prior to Implant
Being aspirin (81-100mg)
Implant
Continue aspirin (81-100mg) and add warfarin, adjusted to achieve INR of until 45-day visit
45 Days Post-Implant
Is LAA seal ≤ 5mm?
Cease Warfarin
And continue aspirin ( mg). Add Clopidogrel (75mg)
6-Month Post-Implant
Cease Clopidogrel and maintain aspirin ( mg) indefinitely
Continue aspirin (81-100mg) and warfarin, adjusted to achieve INR of
Re-assess Seal*
Follow-Up Duration
Has the patient been followed for at least 6 months post-implant with adequate seal?
Cease warfarin and increase aspirin ( mg)
Yes No
*The performance and timing of TEE to re-evaluate the LAA seal is left to physician discretion.
Typical to patient treatment in U.S. clinical trials

38. WATCHMAN Clinical Data
Real World & Expanded Patient Populations

39. ASAP Registry
Prospective study to evaluate LAAC in patients contraindicated for warfarin
Study Objective
Evaluate LAA Closure with WATCHMAN in NVAF patients deemed not suitable for oral anti-coagulation therapy
Study Design
Prospective
Multi-center
Non-Randomized
Primary Endpoint
Ischemic stroke, hemorrhagic stroke, systemic embolism, and CV/unexplained death.
Patient Population
150 patients
Number of Sites
4 Centers
Follow-up
3, 6, 12, 18, and 24 month follow-ups with TEE at 3 and 12 months
Status
All follow-up complete
NCT

40. ASAP Registry – Ischemic Stroke Risk Rate Reduction
Prospective study to evaluate LAAC in patients contraindicated for warfarin
RR 77%
RR 64%
Ischemic Stroke Rate (%/pt-yr)
1.8% - 5 year results
* Data presented is in patients currently contraindicated for LAAC with WATCHMAN in the United States.
Sharma et al. JACC 2016; 67(18):

41. ASAP-TOO
To establish the safety and effectiveness of Watchman for subjects deemed not suitable for anti-coagulation
Study Objective
Evaluate LAA Closure with WATCHMAN in NVAF patients deemed not suitable for oral anti-coagulation therapy
Study Design
Prospective, multi-center
Randomized 2:1 (Watchman vs Control)
Event-driven endpoint
Primary Endpoint
Effectiveness Endpoint
Time to first occurrence of ischemic stroke or systemic embolism
Safety Endpoint
7-day rate of all-cause death, ischemic stroke, systemic embolism, or device- or procedure- related events requiring open cardiac surgery or major endovascular intervention
Patient Population
888
Number of Sites
120 global sites
Follow-up*
3 month with TEE
6,18 month phone visit
12 month with TEE
Bi-annually for years 2-5
Status
Currently Enrolling
Holmes et al. AHJ 2017; 189: NCT
*Brain imaging required at baseline if prior stroke or TIA 41

42. ASAP-TOO Randomization Assignments
Device Group Medical Therapy
Control Group Treatment
Visit Interval
Aspirin
Clopidogrel*
Discharge through
3-month visit
Yes, suggested dose: mg
Yes
Suggested dose: 75mg
3-month visit through 12-month visit**
No, unless other indication
Following the
12-month visit**
Single antiplatelet therapy or no therapy for the duration of the trial at the discretion of the study physician.
Subjects will be allowed to be on dual antiplatelet therapy if indicated.
*Clopidogrel may be substituted with ticagrelor or prasugrel if the subject requires the medication for other indications (e.g. acute coronary syndromes treated with drug eluting stents) or if the subject has a known resistance to clopidogrel.
**Patients are allowed to be on dual antiplatelet therapy (outside of the protocol required 3- months period) if indicated due to a condition other than WATCHMAN implantation.
Holmes et al. AHJ 2017; 189:68-74

43. ASAP-TOO Enrollment Status as of May 2019
GOAL: 888
GOAL: 130
ASAP-TOO
Enrollment Status as of May 2019
Successful execution of this trial will allow for treatment in a patient population that would otherwise be left untreated
NCT

44. EWOLUTION: Registry on WATCHMAN Outcomes in Real-Life Utilization Overview
Study Objective
Collect real-world WATCHMAN LAAO experience outside of selected populations in prior RCT
Study Design
Prospective, single-arm, multi-center registry of the Watchman LAA Closure Technology
Primary Endpoint
Procedural success and safety, incidence of stroke, bleeding, and death after 2 years of FU
Patient Population
1020 patients
Number of Sites
47 throughout Europe, Russia and Middle East
Enrollment
Started October Completed May 2015
Follow-up
Standard practice at participating centers
Normally 1-3 months post-procedure
Annually thereafter for a total of 2 years
Status
All Follow-Up Complete
Boersma LVA et al. Heart Rhythm 2017: 14(9): 44

45. EWOLUTION Complete 2-year patient flow
Informed Consent Obtained
N = 1025
Implant of WATCHMAN
N = 1020
Patients with Successful Watchman Implant
N = 1005
Anatomy Considered not Suitable at Prescreening
N = 5
End of Study < 2 years (N = 221)
Deceased: N = 161
Withdrawn: N = 18
Lost to FU: N = 42
Pts with Completed 2 year FU: N = 784/1005 (78%)
Pts with CT/TEE: N = 835/1005 (83%)
Total Number of CT/TEEs: N = 1145 (average of 1.4/pt)
Boersma LVA et al. Circ Arrhythm Electrophysiol. 2019; 12:e DOI: /CIRCEP

46. EWOLUTION: A High-Risk Patient Population
CHA2DS2-VASc Distribution in EWOLUTION
Number of Patients
Patient Baseline Characteristics
CHA2DS2-VASc Score ≥ 5
49%
HAS-BLED ≥ 3
40%
Major Bleeding/Predisposition Bleeding
39%
Contra-Indication (N)OAC
73%
Majority of Patients
Rate (%) / 100 pt-yrs
These data are for the full cohort of patients, 73% of whom may be contraindicated in the US per current labeling
1Boersma LVA et al. Circ Arrhythm Electrophysiol. 2019; 12:e DOI: /CIRCEP Friberg. EHJ 2012; NICE UK (2014)

47. EWOLUTION 2-Year Follow-Up – Low Annual Thrombo-Embolic Events in Full Cohort
RRR
83%
80%
*Effectiveness in stroke reduction vs. estimated in the absence of therapy for comparable CHA2DS2-VASc scores based on Friberg et al. EHJ 2012
77%
Thromboembolic Events / 100 pt-yrs
These data are for the full cohort of patients, 73% of whom may be contraindicated in the US per current labeling
Boersma LVA et al. Circ Arrhythm Electrophysiol. 2019; 12:e DOI: /CIRCEP

48. EWOLUTION 2-Year Follow-up – Low Annual Bleeding in Full Cohort
RRR 46%
Bleeding Rate / 100 pt-yrs
*Effectiveness in bleeding reduction vs. estimated under VKA therapy for comparable HAS-BLED scores based on Lip et al. JACC 2011
These data are for the full cohort of patients, 73% of whom may be contraindicated in the US per current labeling
Boersma LVA et al. Circ Arrhythm Electrophysiol. 2019; 12:e DOI: /CIRCEP

49. Baseline Characteristics
WASP Registry Real-world clinical outcome data in Asia Pacific and the Middle East
Baseline Characteristics
Study Objective
To compile real-world clinical outcome data in Asia Pacific, Australia and the Middle East
Study Design
Observational Prospective
Non-Randomized
Identical design & study protocol to EWOLUTION
Patient Population
201
Number of Sites
9 sites in Asia Pacific and the Middle East
Primary Analyses
Procedural Success & Safety, Bleeding, All-Cause Mortality, Stroke/TIA/SE
Follow-Up
Patients followed for 2 years after implant
Status
All follow-up complete
Characteristic
Asian
Non-Asian
P-Value
Age
70.7 ± 9.4
70.8 ± 9.4
0.95
Age ≥ 80 (%)
14.0
17.0
0.56
Male (%)
62.6
72.3
0.18
CHA2DS2-VASc Score
4.1 ± 1.7
3.7 ± 1.6
0.08
HAS-BLED Score
2.1 ± 1.3
2.1 ± 0.9
0.66
HAS-BLED Score ≥ 3 (%)
34.6
26.6 NR
History TIA/Stroke (%)
30.8
45.7
0.04
Paroxysmal AF Pattern (%)
54.2
47.3
0.4
Phillips KP et al. ILC Heart & Vasculature 2019; 23(100358)

50. Ischemic Stroke/TIA/SE
WASP – Efficacy Outcomes at 2 Years Demonstrated long-term efficacy for stroke in a primarily Asian cohort
Ischemic Stroke/TIA/SE
Full Cohort
(N=201)
Percent / 100 pt-yrs
Asians
(N=107)
77% RR
89% RR
62% RR
Non-Asians
(N=94)
The Asian population has been shown to have an increased stroke risk commencing from a younger age1,
as well as substantially higher rates of intracranial bleeding2
Effectiveness in stroke reduction vs. estimated in the absence of therapy for comparable CHA2DS2-VASc scores based on Friberg et al. EHJ 2012
A portion of the patients included in these data were likely contraindicated in the US per current labeling
1Chao TF et al. Stroke 2016; 47: Shen JF et al. J. Am. Coll. Cardiol 2007; 50: Phillips KP et al. ILC Heart & Vasculature 2019; 23(100358)

51. WASP – Safety Outcomes at 2 Years Significant reduction in Bleeding Events, especially pronounced in the Asian population
Major Bleeding
Full Cohort
(N=201)
Percent / 100 pt-yrs
Non-Asians
(N=94)
Asians
(N=107)
49% RR
77% RR
89% RR
29% RR
14% RR
The Asian population has been shown to have an increased stroke risk commencing from a younger age1, as well as substantially higher rates of intracranial bleeding2
Effectiveness in bleeding reduction vs. estimated under VKA therapy for comparable HAS-BLED scores based on Lip et al. JACC 2011
A portion of the patients included in these data were likely contraindicated in the US per current labeling
1Chao TF et al. Stroke 2016; 47: Shen JF et al. J. Am. Coll. Cardiol 2007; 50: Phillips KP et al. ILC Heart & Vasculature 2019; 23(100358)

52. > 92% warfarin cessation after 45 days, > 99% after 1 year1
WATCHMAN Clinical Summary
A safe alternative to long-term warfarin therapy which offers comparable stroke risk reduction and enables patients to stop taking warfarin1,2
Demonstrated statistically superior reductions in disabling/fatal strokes, major non- procedure related bleeding and cardiovascular death compared to warfarin2,3,5
Demonstrated 95% implant success rate and a 1.5% major procedural complication rate with both new and experienced operators4
> 92% warfarin cessation after 45 days, > 99% after 1 year1
1Holmes, DR et al. JACC 2014; 64(1): Holmes, DR et al. JACC 2015; 65(2): Price MJ, et al. JACC: CV Interv 2015; 8(15): Reddy VY, et al. JACC 2017; 69(3): Reddy VY, et al. JACC 2017; 70(24):

53. 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: