Registry on WATCHMAN Outcomes in Real-Life Utilization
Conditions: Patients With Atrial Fibrillation at Risk for Thrombus Formation, Thromboembolism, Stroke
Sponsor: Boston Scientific Corporation

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EWOLUTION 
REgistry on WATCHMAN Outcomes in Real-Life Utilization 
 
 
 
 
 
Clinical Protocol 
07-13 
 
 
 
 
 
Sponsored By:  
 
Guidant Europe 
a Boston Scientific Company 
Green Square, Lambroekstraat 5D, 
1831 Diegem, 
Belgium 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should 
be held confidential and maintained in a secure location.  
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 

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Contact Information 
Role 
Contact  
Clinical Contact 
Elke Sommerijns 
Clinical Trial Manager 
Guidant Europe, a Boston Scientific company 
Green Square, Lambroekstraat 5D 
1831 Diegem 
Belgium 
Tel. +32 2 4167197 
elke.sommerijns@bsci.com 
 
Lynnett Voshage-Stahl 
Director, CRV Clinical  
Boston Scientific Corporation  
4100 Hamline Avenue North  
St. Paul, MN 55112-5798  
Tel: +1 651-582-2994  
lynnett.voshage-stahl@bsci.com 
 
Clinical Contributors 
Aruna Vedala, Clinical Trial Manager 
Boston Scientific Corporation  
Coordinating 
Principal Investigator 
Dr. Lucas Boersma 
St. Antonius Ziekenhuis 
Koekoekslaan 1 
PO 2500, 3430 EM 
Nieuwegein, The Netherlands 
 
Original Release: 15 July 2013  
Current Version:  03 October 2014 
 
 
 
 
 
 
 
 
 
 

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2. Protocol Synopsis 
EWOLUTION - REgistry on WATCHMAN Outcomes in Real-Life Utilization 
Objective(s) 
• To compile real-world clinical outcomes data for WATCHMAN LAA 
(Left Atrial Appendage) Closure Technology in patients who are 
implanted with the WATCHMAN device in a commercial clinical setting. 
• To collect real-world usage data that may be needed for reimbursement of 
WATCHMAN technology in certain countries. 
Marketing 
Performance 
Expectation  
The WATCHMAN LAA Closure Technology is designed to prevent 
embolization of thrombi that may form in the LAA, thereby preventing the 
occurrence of ischemic stroke and systemic thromboembolism. 
Test Device 
WATCHMAN LAA Closure Technology 
Device Sizes 
21mm, 24mm, 27mm, 30mm, 33mm  
Study Design 
This is an observational, prospective, non-randomized, multicenter study. 
Planned Number 
of Subjects 
Approximately 1000 subjects will be enrolled in the study.  
Planned Nr of 
Centers/Countries 
Up to 70 sites in the International (Outside of US) region.  
Primary Endpoint 
Primary analyses may include, but will not be limited to, the following: 
procedural complications, incidence of stroke and death. Descriptive 
statistics will be used for baseline, procedure and follow-up data collected 
through the study.  
Study Duration 
Enrolment is expected to be completed in 21 months; therefore the total 
study duration is estimated to be 48 months.  
Follow-up (FU) 
Schedule 
Each patient will be followed for a period of two years after enrolment 
according to the schedule and standard practice at the enrolling centers. 
There will be no additional visits, nor procedures, for subjects who 
participate in the study. Subjects are expected to be followed at implant, then 
at one post-implant visit (typically between 1-3 months of implant), and then 
annually through 2 years post implant. An intermediate visit may be a 
scheduled in a number of patients, per physician discretion. In order to 
reliably capture patient status at study end a FU window of 24 ± 3 months 
will be considered acceptable for scheduling the last visit. 
For subjects who are not scheduled to visit the clinic for a follow-up, a 
subject contact (e.g. phone call) will ensure capture of the endpoint related 
information, however it is recommended to perform an in-office visit for at 
least the first annual visit. 
 
 
 

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EWOLUTION - REgistry on WATCHMAN Outcomes in Real-Life Utilization 
Data Collection Overview 
 
Data Collected 
BASELINE 
IMPLANT 
Follow Up 
Post-
implant 
Visit* 
FU 
office 
visit 
FU 
phone 
visit 
Informed Consent  
X 
 
 
 
 
Inclusion/Exclusion  
X 
 
 
 
 
Demographic data 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
LAA imaging (e.g. TEE) 
 
X 
X§ 
X** 
 
Medication Regimen 
X 
X 
X 
X 
X 
Current status and Vital Signs 
X 
X 
X 
X 
 
Adverse Event Reporting 
X 
X 
X 
X 
X 
 
*expected 1-3 month from implant depending on center’s practice  
§ Control TEE/CT is clinical standard after the Watchman procedure to ensure 
sealing and exclude thrombus on the device prior to stop dual platelet inhibition or 
warfarin 
** collected only if performed, according to center’s practice 
Key Inclusion 
Criteria 
A subject may be enrolled in the study if all of the following inclusion 
criteria are met, provided no exclusion criteria are met:  
1. Patients who are eligible for a WATCHMAN device according to 
current international and local guidelines (and future revisions) and per 
physician discretion; 
2. Patients who are willing and capable of providing informed consent, 
participating in all testing associated with this clinical investigation at an 
approved clinical investigational center; 
3. Patients whose age is 18 years or above, or of legal age to give informed 
consent specific to state and national law.  
Key Exclusion 
Criteria 
Subjects will be excluded from the study if they meet any of the following 
criteria: 
1. Patients who are currently enrolled in another investigational study or 
registry that would directly interfere with the current study, except when 
the patient is participating in a mandatory governmental registry, or a 
purely observational registry with no associated treatments. Each 
instance should be brought to the attention of the sponsor to determine 
eligibility. 
2. Women of childbearing potential who are, or plan to become, pregnant 
during the time of the study (method of assessment upon physician’s 
discretion); 

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EWOLUTION - REgistry on WATCHMAN Outcomes in Real-Life Utilization 
3. The subject is unable or not willing to complete follow-up visits and 
examination for the duration of the study. 
Statistical Methods 
Statistical Test 
Method 
No formal pre-specified hypotheses will be tested. However, a variety of 
statistical modeling methods may be utilized in order to assess associations 
between the likelihood of each of the three outcomes and the pre-specified 
patient and procedural characteristics, including multivariate logistic 
regression and classification and regression tree models. 
Sample Size 
Parameters 
This is a prospective, multicenter non-randomized observational study with 
no formal pre-specified hypothesis test.  All subjects will be followed for up 
to 2 years or until the study is terminated.   
A sample size of up to 1000 subjects was chosen to assess incidence of rare 
events with a large degree of precision.  The table below provides the two-
sided 95% confidence interval assuming an event rate of 5%. 
 
Two-Sided Confidence Interval by Sample Size: 
 
Sample Size 
95% CI  
500 
5% ± 1.9% 
750 
5% ± 1.6% 
1000 
5% ± 1.4% 
 
 
 

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3. Table of Contents 
1. 
TITLE PAGE  ........................................................................................................................ 1 
2. 
PROTOCOL SYNOPSIS ......................................................................................................... 3 
3. 
TABLE OF CONTENTS ......................................................................................................... 6 
3.1. Table of Figures ....................................................................................................... 9 
3.2. Table of Tables ......................................................................................................... 9 
4. 
INTRODUCTION ................................................................................................................. 10 
i) 
Background ............................................................................................................ 10 
ii) 
WATCHMAN Therapy ........................................................................................ 11 
iii) 
WATCHMAN Clinical Study Experience ........................................................... 11 
5. 
DEVICE DESCRIPTION ...................................................................................................... 12 
i) 
WATCHMAN Device ............................................................................................ 13 
ii) 
WATCHMAN Delivery System ........................................................................... 13 
iii) 
WATCHMAN Access Sheath ............................................................................... 14 
6. 
OBJECTIVES ...................................................................................................................... 14 
7. 
ENDPOINT ANALYSIS ........................................................................................................ 14 
8. 
DESIGN .............................................................................................................................. 14 
8.1. Scale and Duration ................................................................................................ 14 
8.2. Justification for the Study Design ........................................................................ 15 
9. 
SUBJECT SELECTION ........................................................................................................ 15 
9.1. Study Population and Eligibility .......................................................................... 15 
9.2. Inclusion Criteria ................................................................................................... 15 
9.3. Exclusion Criteria .................................................................................................. 15 
10. SUBJECT ACCOUNTABILITY ............................................................................................. 16 
10.1. Enrolment ............................................................................................................... 16 
10.2. Withdrawal ............................................................................................................. 16 
10.3. Subject Status and Classification (please refer to Figure 2 for a summary) .... 16 
11. STUDY METHODS .............................................................................................................. 18 

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11.1. Data Collection ....................................................................................................... 18 
11.2. Informed Consent .................................................................................................. 19 
11.3. Study Candidate Baseline ..................................................................................... 19 
11.4. LAA Imaging (e.g. TEE/CT/MRI) ....................................................................... 20 
11.5. Implant Procedure ................................................................................................. 20 
11.6. Follow-up Procedures ............................................................................................ 21 
i) 
In-Hospital Visit ..................................................................................................... 21 
ii) 
Subject Contact ...................................................................................................... 22 
11.7. Study Completion .................................................................................................. 23 
11.8. Source Documents ................................................................................................. 23 
12. STATISTICAL CONSIDERATIONS ....................................................................................... 23 
12.1. Sample Size Justification ....................................................................................... 23 
12.2. Statistical Analysis ................................................................................................. 24 
13. DATA MANAGEMENT ........................................................................................................ 25 
13.1. Data Collection, Processing, and Review ............................................................. 25 
13.2. Data Retention ....................................................................................................... 25 
14. AMENDMENTS ................................................................................................................... 26 
15. DEVIATIONS ...................................................................................................................... 26 
16. COMPLIANCE .................................................................................................................... 26 
16.1. Statement of Compliance ...................................................................................... 26 
16.2. Investigator Responsibilities ................................................................................. 26 
16.2.1. Delegation of Responsibility ..................................................................... 28 
16.2.2. Investigator Records .................................................................................. 28 
16.3. Institutional Review Board/ Ethics Committee .................................................. 29 
16.4. Sponsor Responsibilities ........................................................................................ 29 
16.4.1. Sponsor Records ........................................................................................ 29 
16.5. Insurance ................................................................................................................ 30 
17. MONITORING .................................................................................................................... 30 
18. POTENTIAL RISKS AND BENEFITS .................................................................................... 30 

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18.1. Risks Associated with the study............................................................................ 30 
18.2. Risks Associated with a standard WATCHMAN Implant & Procedure ......... 30 
18.3. Risk Minimization Actions ................................................................................... 32 
18.4. Anticipated Benefits............................................................................................... 32 
19. INFORMED CONSENT ........................................................................................................ 32 
20. SAFETY REPORTING ......................................................................................................... 34 
20.1. Investigator Reporting Requirements ................................................................. 35 
20.2. Boston Scientific Device Deficiencies ................................................................... 37 
20.3. Reporting to Regulatory Authorities / IRBs / ECs / Investigators .................... 37 
21. COMMITTEES .................................................................................................................... 37 
21.1. Safety Monitoring Process .................................................................................... 37 
21.2. Executive/Steering Committee ............................................................................. 37 
22. SUSPENSION OR TERMINATION ........................................................................................ 38 
23. PUBLICATION POLICY ...................................................................................................... 38 
24. BIBLIOGRAPHY ................................................................................................................. 40 
APPENDIX A - DEFINITIONS ..................................................................................................... 42 
A.1 Stroke/TIA definitions ............................................................................................. 42 
A.2 Classification of Bleeding events ............................................................................. 42 
 
 
 

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3.1. Table of Figures 
Figure 1: WATCHMAN Device ......................................................................................... 13 
Figure 2: Subject Status and Data Collection Flow Chart ............................................... 18 
 
3.2. Table of Tables 
Table 1: Clinical Studies of the WATCHMAN Device .................................................... 11 
Table 2: Data Collection Overview ................................................................................... 19 
Table 3: Two-Sided Confidence Interval by Sample Size ................................................ 23 
Table 4: Covariates of Interest .......................................................................................... 24 
Table 5: Adverse Event Definitions .................................................................................. 34 
Table 6: Investigator Reporting Requirements .................................................................. 36 
 

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4. Introduction 
i) Background 
Atrial fibrillation (AF) is one of the most common abnormal rhythm disturbances and 
affects approximately 5.5 million people worldwide, including 10% of people older than 
75 years1. The most debilitating consequence of AF is thrombus formation from stagnant 
blood flow leading to thromboembolism and stroke.  As such, the rate of ischemic stroke 
attributed to non-valvular AF is estimated to average 5% per year which is 2-7 times that 
of those without AF2. 
Treatment with warfarin therapy for the prevention of thromboemboli originating in the 
left atrial appendage has been well documented3-5. Warfarin therapy targeting an 
International Normalized Ratio (INR) between 2.0 – 3.0 is considered the gold standard 
treatment today for patients with non-valvular AF for prevention of stroke.  While 
warfarin has remained the optimum treatment for many years, there are numerous 
challenges with the drug, such as frequent need for monitoring and dosage adjustments, 
dietary and metabolic interactions, and concerns of patient compliance.  Additionally, the 
potential for frequent and fatal bleeding are high concerns for patients and caregivers and 
often it is found this drug is not well tolerated.  
Currently available alternatives to warfarin are the new oral anticoagulants (NOACs) 
which include dabigatran, rivaroxaban, apixaban. Unlike Warfarin,  NOACs can be 
administered without the need for monitoring, have fewer food and drug interactions and 
provide an improved efficacy/safety ratio, Dabigatran at the dose of 150 mg twice daily is 
shown to be superior to warfarin in prevention of stroke and systemic thromboembolism, 
has a favorable safety profile including  significantly less intracranial bleeding and 
comparable extracranial bleeding, and is associated with less cardiovascular mortality6-9. 
Rivaroxaban at a daily dose of 20 mg is shown to be noninferior to warfarin in prevention 
of stroke or systemic embolism. The risk of major bleeding is not significantly different 
for rivaroxaban vs warfarin, however, intracranial and fatal bleeding is less frequent with 
rivaroxaban10. In comparison to warfarin, apixaban at a dose of 5 mg twice daily is also 
shown to be superior in prevention of stroke and systemic thromboembolism, causes less 
bleeding, and is associated with a lower mortality rate11. 
As the risk of stroke increases with age and the disability and tolerance concerns with 
available drug therapy 
persist, the need for permanent 
protection against 
thromboembolism in AF patients remains unmet. The sponsor has developed the 
WATCHMAN® Left Atrial Appendage Closure (LAA) Device, a permanent implantable 
device to seal off the left atrial appendage, the location where the vast majority of thrombi 
originate in AF patients.  This device may provide an alternative to warfarin therapy in 
non-valvular AF patients who require thromboembolic protection. The current study is 
designed to compile real-world clinical outcomes data for WATCHMAN LAA Closure 
Technology in subjects with non-valvular AF.  

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ii) WATCHMAN Therapy 
The WATCHMAN® LAA Closure Technology is intended for patients with non-valvular 
atrial fibrillation who require treatment for potential thrombus formation.  
The implanted component of the system, hereafter referred to as the WATCHMAN 
device, is an approved commercially available novel device designed to prevent the 
embolization of thrombi that may form in the LAA.  The WATCHMAN device may 
prevent the occurrence of ischemic stroke and systemic thromboembolism in patients with 
non-valvular AF who require treatment for potential thrombus formation.  It may also 
reduce the risk of life-threatening bleeding events such as hemorrhagic stroke by 
potentially removing the need for anticoagulation therapy.  The WATCHMAN device is 
manufactured by Boston Scientific, received CE Mark in October 2005, and is under IDE 
in the United States (U.S.).   
iii) WATCHMAN Clinical Study Experience 
Clinical evaluation of the WATCHMAN LAA Closure Technology has been ongoing 
since 2002, with all U.S. studies conducted under IDE #G020312. Table 1 lists the 
clinical studies conducted with the WATCHMAN device.   
 
Table 1: Clinical Studies of the WATCHMAN Device 
 
Study 
Dates of Enrolment 
Enrolled 
Subjects 
Sites 
Follow-Up 
Pilot  
(feasibility study) 
Aug 2002 – Jan 2005 
66 
8 
U.S. subjects completed 5 
years; OUS subjects 
completed up to 9 years. 
PROTECT AF  
(pivotal study) 
Feb 2005 – Jun 2008 
800 
59 
Ongoing through 5 years 
CAP Registry 
Aug 2008 – Jun 2010 
566 
26 
Ongoing through 5 years 
ASAP 
(feasibility study) 
Jan 2009 – Nov 2011 
150 
4 
Ongoing through 2 years 
PREVAIL  
(pivotal study) 
Nov 2010 – Jun 2012 
461 
41 
Ongoing through 5 years 
CAP2 Registry 
Sep 2012 - ongoing 
Up to 
1500 
Up to 
60 
Ongoing through 5 years 
 
The first pilot study demonstrated that the WATCHMAN device was safe and met the 
performance criteria for use in subjects with non-valvular atrial fibrillation.  
The first pivotal study, WATCHMAN Left Atrial Appendage System for Embolic 
PROTECTion in Patients with Atrial Fibrillation12 (PROTECT-AF), demonstrated non-

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inferiority of the WATCHMAN device to long-term warfarin therapy for the primary 
efficacy endpoint of stroke, systemic embolism and cardiovascular death.  
Most recent data analysis of The PROTECT AF13 trial has shown that the WATCHMAN 
device achieved superiority for the combined endpoint of all stroke, cardiovascular or 
unexplained death and systemic embolism (for Bayesian analysis, posterior probabilities 
are used to determine superiority; > 95% represents superiority). 
•The observed primary efficacy event rate was 2.3 percent and 3.8 percent in the 
WATCHMAN and control groups, respectively, demonstrating a 40 percent relative 
risk (RR) reduction in primary efficacy in the WATCHMAN group (RR = 0.60, 
posterior probability of superiority = 96 percent). 
Secondary analysis also showed a relative risk reduction and superiority to control for all-
cause mortality and cardiovascular mortality.  
•All-Cause Mortality: the WATCHMAN group was superior to the control group, 3.2 
percent to 4.8 percent respectively, representing a 34 percent relative risk reduction 
in all-cause mortality in the WATCHMAN group (Hazard ratios [HR] = 0.66, 
p=0.0379).  
•Cardiovascular Mortality: the WATCHMAN group was superior to the control 
group, 1.0 percent and 2.4 percent respectively, representing a 60 percent relative risk 
reduction in cardiovascular death in the WATCHMAN group (HR = 0.40, p=0.0045). 
The Continued Access to PROTECT Registry14 (CAP Registry) provided continued 
access of the WATCHMAN device to PROTECT-AF investigators and demonstrated a 
decrease in procedural complications of pericardial effusion with tamponade, cardiac 
perforation and device embolization (1.2%, 0.2%, 0%, respectively).  
The second pivotal study, Prospective Randomized Evaluation of the WATCHMAN 
LAA Closure Device In Patients with Atrial Fibrillation Versus Long Term Warfarin 
Therapy (PREVAIL), was conducted to provide additional information on the implant 
procedure and complication rates associated with the device.  
The ASA Plavix Feasibility Study With WATCHMAN Left Atrial Appendage Closure 
Technology (ASAP) study was a feasibility study conducted in Europe to characterize the 
performance of the WATCHMAN device in non-valvular atrial fibrillation (AF) subjects 
with contraindications to warfarin therapy. 
The Continued Access Protocol (CAP2) is a prospective, non-randomized, multicenter 
study to allow continued access to the WATCHMAN LAA Closure Technology during 
the data analysis, reporting and review of the PREVAIL pivotal study Pre-Market 
Application by FDA.   
5.  Device Description 
The WATCHMAN device is designed to be permanently implanted at or slightly distal to 
the ostium (opening) of the LAA to prevent embolization of blood clots formed within the 
trabeculated LAA.  The placement procedure can be performed under general or 

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conscious sedation in a catheterization or electrophysiology (EP) laboratory setting using 
standard transseptal technique under fluoroscopic and echocardiographic guidance.  
The WATCHMAN LAA Closure Technology is a three-component system which 
includes the WATCHMAN LAA Closure Device (WATCHMAN device), the 
WATCHMAN Delivery System and the WATCHMAN Access Sheath.  
i) WATCHMAN Device 
The WATCHMAN device is comprised of a self-expanding nitinol frame structure with 
fixation anchors around the device perimeter and a permeable polyester fabric that covers 
the atrial facing surface of the device (Figure 1).  The device is constrained within the 
Delivery System until deployment into the LAA. The WATCHMAN device is available 
in various sizes to accommodate a range of LAA ostial diameters.  The device size, 
measured in mm, is the diameter of the device at its maximum dimension in an 
uncompressed (fully expanded) state.  An appropriate device size is selected based on 
LAA 
measurements 
obtained 
utilizing 
Fluoroscopy 
and 
Transesophageal 
Echocardiography (TEE).  
 
 
Figure 1: WATCHMAN Device 
 
 
ii) WATCHMAN Delivery System 
The delivery catheter consists of an inner core wire with a reinforced braided jacket that is 
connected to the deployment knob at the proximal end and a screw thread assembly at the 
distal end.  The outer sheath has an overall profile of 12 French.  
The WATCHMAN device is pre-loaded and is deployed by loosening the valve on the 
Delivery System and retracting the outer sheath.  The WATCHMAN device can be 
partially recaptured and redeployed if the device is too distal.  If the device is deployed 
too proximal, it can be fully recaptured. The device is released by rotating the device 
deployment knob counter clockwise. 

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iii) WATCHMAN Access Sheath 
The 14 French transseptal Access Sheath is utilized to gain access to the LAA and serves 
as a conduit for the Delivery System.  The distal end of the Access Sheath is available in 
various curve styles to assist with placement of the sheath into the LAA.  Various curve 
styles allow for coaxial placement of the sheath into the LAA. The distal tip contains a 
marker band for in situ visualization as well as sizing marker bands used to gauge if the 
Access Sheath is positioned at the appropriate depth in the LAA based on the device size 
selected.   
The Access Sheath and dilator are utilized to gain access to the LAA after initial 
transseptal access into the left atrium has been established.  Once the Access Sheath is 
positioned into the left atrium and the dilator has been removed, it then serves as a 
conduit for the Delivery System.  The Delivery System is introduced into the Access 
Sheath and the components snap together to act as one during device implantation.   
6. Objectives 
The objective of the study is to compile real world clinical data on the use of the 
WATCHMAN LAA Closure Technology in a commercial clinical setting. 
The study aims to obtain additional clinical data on procedural success and complications, 
as well as information about long-term patient outcomes, including clinical data on 
incidence of stroke/TIA. 
The collected real-world data may be needed for reimbursement of WATCHMAN 
technology in certain countries. 
7. Endpoint Analysis 
Primary analyses may include, but will not be limited to, the following: procedural 
complications, incidence of stroke and death. Descriptive statistics will be used for 
baseline, procedure and follow-up data collected through the study.  
8. Design 
This WATCHMAN Registry is an observational, prospective, non-randomized, 
multicenter study.  
8.1. Scale and Duration 
Approximately 1000 subjects will be enrolled at up to 70 sites in the International 
(Outside the US) region.  
 
Each patient will be followed for a period of two years after implant according to the 
schedule. There will be no additional visits for subjects who participate in the study.  
 

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It is anticipated that enrolment will be conducted over a period of 21 months; therefore 
the total study duration is estimated to be 48 months. 
8.2. Justification for the Study Design 
This is a purely observational post-market data collection designed to compile real-world 
clinical outcomes data for WATCHMAN LAA Closure Technology. The implant of the 
device is done according to the patient clinical indications, regardless of participation in 
the study. The post-implant TEE (or alternative imaging methods) is also a clinical 
standard after the Watchman procedure to ensure sealing and exclude thrombus on the 
device prior to stop dual platelet inhibition or warfarin. The patients are followed per 
standard of care (no additional burden for the patient like additional invasive examination 
or additional follow-up). 
9. Subject Selection  
9.1. Study Population and Eligibility  
Any patient, who meets all the inclusion criteria, does not meet any of the exclusion 
criteria, and who provides written informed consent may be enrolled in the study. The 
subjects selected for participation will be from the investigator’s general patient 
population. The investigator has the responsibility for screening all potential patients and 
selecting those who meet study inclusion/exclusion criteria as described in sections 9.2 
and 9.3. 
9.2. Inclusion Criteria 
A subject may be enrolled in the study if all of the following inclusion criteria are met, 
provided no exclusion criteria (see section 9.3) are met:  
 
1. Patients who are eligible for a WATCHMAN device according to current 
international and local guidelines (and future revisions) and per physician 
discretion; 
2. Patients who are willing and capable of providing informed consent, participating 
in all testing associated with this clinical investigation at an approved clinical 
investigational center; 
3. Patients whose age is 18 years or above, or of legal age to give informed consent 
specific to state and national law. 
9.3. Exclusion Criteria 
Subjects will be excluded from the study if they meet any of the following criteria: 
1. Patients who are currently enrolled in another investigational study or registry that 
would directly interfere with the current study, except when the patient is 
participating in a mandatory governmental registry, or a purely observational registry 
with no associated treatments. Each instance should be brought to the attention of the 
sponsor to determine eligibility. 

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2. Women of childbearing potential who are, or plan to become, pregnant during the 
time of the study (method of assessment upon physician’s discretion); 
3. The subject is unable or not willing to complete follow-up visits and examination for 
the duration of the study. 
 
10. Subject Accountability 
10.1. Enrolment 
Subjects who meet the eligibility criteria as per 9.2 and 9.3, have signed and dated the 
Informed Consent Form and actually undergo a WATCHMAN implant procedure are 
considered enrolled in the study. Baseline data from subjects who meet the eligibility 
criteria as per 9.2 and 9.3, have signed and dated the Informed Consent Form but do not 
eventually undergo a WATCHMAN implant procedure are collected for epidemiological 
reasons, to better characterize the population. The start of the WATCHMAN implant 
procedure is considered the insertion of the WATCHMAN Access Sheath. 
10.2. Withdrawal 
Every effort should be made to retain subject enrolment for the duration of the study.  
During the informed consent process subjects should be fully informed of the data 
collection requirements and duration, and should only be enrolled if willing to fully 
participate in it. All subjects enrolled in the clinical study must be accounted for and 
documented. Reasons for withdrawal may include physician discretion, subject choice to 
retire consent, loss to follow-up, or death. In the event a subject does decide to withdraw 
from the study, every effort should be made to obtain full information on any on-going 
adverse events.   
Subjects should only be considered lost to follow-up after significant effort has been 
made to contact the subject.  At a minimum there should be 3 documented telephone 
contact attempts and one certified letter sent to the subject’s last known residence. Subject 
withdrawal and lost to follow-up will be documented on the “End of Study” CRF. For 
subjects who are “lost-to-follow-up” the investigator/center should make documented 
attempts to contact the subject prior to completion of the applicable CRF. Additional data 
may no longer be collected after the point at which a subject has been withdrawn from the 
study or withdraws his/her consent, for whatever reason. All open adverse events should 
be closed or documented as chronic. Data collected up to the point of subject withdrawal 
may be used, unless any local regulations apply which require removal of the data. 
 
 
10.3. Subject Status and Classification (please refer to Figure 2 for a summary) 
Consent Ineligible 

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A subject who has signed informed consent but is found to not meet eligibility criteria 
will be classified as “Consent Ineligible”. There are no FU or adverse event reporting 
requirements for consent ineligible subjects. Subjects determined to be Consent Ineligible 
according to statements above do not count towards the enrolment ceiling and will not be 
used for analysis of the endpoints. The original signed Informed Consent must be 
maintained in the center’s administrative file.   
 
Intent 
A subject who signs informed consent, meets eligibility criteria, but then does not 
undergo an implant of a WATCHMAN device will be classified as “Intent”. This 
definition includes subjects that do not meet echocardiographic criteria for a 
WATCHMAN implant at the implant TEE/CT evaluation (e.g. a thrombus has developed 
in the LAA, inappropriate LAA size). These patients may be withdrawn immediately, 
unless re-assessment of the criteria is planned.  
Subjects who have been consented, but not yet implanted at the time of enrolment closure 
will also be classified as Intent. There are no FU or adverse event reporting requirements 
for Intent subjects. Intent subjects do not count towards the enrolment ceiling and will not 
be used for analysis of the endpoints. The original signed Informed Consent must be 
maintained in the center’s patient file. For these subjects, the eCRFs in the “Baseline” 
folder and a “Patient Status” form must be completed. Subjects who become Intents due 
to death before the implant procedure must have the death documented. 
 
Attempt 
A subject who signs informed consent, meets eligibility criteria and has had the 
WATCHMAN Access Sheath inserted to implant the device, but eventually does not 
receive a WATCHMAN device will be classified as “Attempt”. These subjects may be 
withdrawn, unless a re-implant of a study device is planned, per physician discretion. 
These subjects will be handled as “Implant” (see next section), if the re-implant is 
successful. Subjects who eventually have not received a WATCHMAN device at the time 
of enrolment closure will remain classified as “Attempt” and be withdrawn. There are no 
FU requirements for Attempt subjects; however, adverse events will be collected up to the 
point of subject withdrawal. Attempt subjects count towards the enrolment ceiling and 
will be used for analyses of the endpoints. The original signed Informed Consent must be 
maintained in the center’s study file and the following forms must be completed: 
• eCRFs in the “Baseline” and “Implant” folders 
• “Adverse Event” forms for any adverse event that occurs after signing the 
Informed Consent, up to the point of subject withdrawal. 
• “Patient Status” form for withdrawal, when applicable. 
The date at which the patient status form has been completed will be the point of subject 
withdrawal.  
 
Implant 
A subject who is successfully implanted with the WATCHMAN device will be classified 
as “Implant”. These subjects are followed in accordance with the FU schedule and 

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included in all study analyses.  All applicable case report forms per the protocol must be 
completed. The original signed Informed Consent and any relevant documentation must 
be maintained in the center’s patient file. 
 
Figure 2: Subject Status and Data Collection Flow Chart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11. Study Methods 
11.1. Data Collection 
To ensure data quality and completeness, all required data will be recorded on case report 
forms (CRFs) provided by the sponsor.  Data will be entered onto electronic case report 
forms by the investigational site or designee. Case Report Forms should be completed 
accurately during and in a timely manner after any visit in the study.  The Principal 
Investigator or appointed designee must review the case report forms and sign them, 
certifying their accuracy.  Completed case report forms should be submitted to the 
sponsor within two weeks of completion of a study visit.  
Each patient will be followed for a period of two years after implant according to the 
schedule and standard practice at the enrolling centers. There will be no additional visits, 
nor procedures, for subjects who participate in the study. Subjects are expected to be 
followed at implant, then at one post-implant visit (typically between 1-3 months of 
implant), and then annually through 2 years post implant. An intermediate visit may be a 
scheduled in a number of patients, per physician discretion. In order to reliably capture 
Informed consent 
obtained 
LAA criteria 
met? 
Implant of WATCHMAN 
 
*** subject is enrolled *** 
Reassess per 
physician’s discretion 
NO 
YES 
Device implanted 
Device not implanted 
Follow-up according to 
center’s practice 
Withdrawal 
(Attempt) 
reimplant 
Withdrawal 
(Intent) 

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patient status at study end a FU window of 24 ± 3 months will be considered acceptable 
for scheduling the last visit. 
For subjects who are not scheduled to visit the clinic for a follow-up, a subject contact 
(e.g. phone call) will ensure capture of the endpoint related information, however it is 
recommended to perform an in-office visit for at least the first annual visit. 
 
 Table 2 provides an overview of the data to be collected at each visit. 
 
Table 2: Data Collection Overview 
 
Data Collected 
BASELINE 
IMPLANT 
Follow Up 
Post-
implant 
Visit* 
FU 
office 
visit 
FU 
phone 
visit 
Informed Consent  
X 
 
 
 
 
Inclusion/Exclusion  
X 
 
 
 
 
Demographic data 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
LAA imaging (e.g. TEE) 
 
X 
X§ 
X** 
 
Medication Regimen 
X 
X 
X 
X 
X 
Current status and Vital Signs 
X 
X 
X 
X 
 
Adverse Event Reporting 
X 
X 
X 
X 
X 
 
*expected 1-3 month from implant depending on center’s practice  
§ Control TEE/CT is clinical standard after the Watchman procedure to ensure sealing and exclude 
thrombus on the device prior to stop dual platelet inhibition or warfarin 
** collected only if performed, according to center’s practice 
11.2. Informed Consent 
In order to determine eligibility of a subject, the investigator needs to implement the 
consent process and verify and document the subject meets the inclusion/exclusion 
criteria. Informed consent is required from all patients (or their legal representatives) prior 
to the patient’s participation in the study. The patient should be given ample time to 
consider participation and ask questions if necessary. An approved informed consent form 
shall be signed and personally dated by the subject (or legal representative). The original, 
signed document is to be kept with the subject’s file and a copy must be provided to the 
subject.   
11.3. Study Candidate Baseline  
Only those subjects who provide consent and meet all of the study enrolment criteria may 
be enrolled and will have Baseline data collected.  Subjects who provide informed 

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consent but do not meet all of the study enrolment criteria will be considered Consent 
Ineligible.  
The data collection at Baseline includes: 
• Demographic data, including: age at time of consent, gender;  
• Risk factors, including those used to calculate HAS-BLED, CHADS2 and 
CHA2DS2-VASc scores; 
• Medical and cardiac history, including: cardiovascular diseases; prior history of 
ischemic stroke, hemorrhagic stroke or TIA; previous cardiac procedures; history 
of bleeding; indication for LAA occlusion; 
• Current medical status; vital signs; AF status (paroxysmal, persistent, permanent);  
• Current medication regimen for the use of antiplatelet and anticoagulation 
medications; 
• Adverse Events, if applicable. 
11.4. LAA Imaging (e.g. TEE/CT/MRI) 
Prior to implantation with the WATCHMAN device, an implant TEE (or alternative 
imaging method) is a clinical standard to confirm there is no thrombus in the LAA or left 
atrium. The implant LAA imaging will also allow the investigator to obtain proper 
measurements of the LAA to correctly size the device, confirm device release criteria are 
met prior to device release, and to confirm adverse events have not occurred during the 
implant procedure (i.e., pericardial effusion). If an intracardiac thrombus is visualized by 
echocardiographic imaging, the patients will not be implanted. Re-assessment may be 
scheduled per physician’s discretion.  
The first control LAA imaging, normally between 1-3 months post-implant, is a clinical 
standard after the WATCHMAN procedure, it is conducted to assess flow through and 
around the WATCHMAN device, to ensure sealing and to verify there is no thrombus on 
the surface of the device prior to stopping dual platelet inhibition or warfarin. Additional 
LAA imaging may be conducted at the discretion of the investigator and according to 
center’s practice.  
Certain information from TEEs conducted during the course of the study will be captured 
on the study case report forms, including: heart rhythm; valve status; pericardial status; 
atrial septum characteristics; LAA size and type of anatomy; thrombus assessment.  
11.5. Implant Procedure 
The implant procedure should be performed using standard of care methods established 
by the investigational center (e.g. sterile technique, personnel requirements, etc.).  
Implantation of the WATCHMAN LAA Closure Device should only be performed by 
physicians trained in percutaneous and transseptal procedures who have completed the 
WATCHMAN training program. Refer to the WATCHMAN LAA Closure Technology 

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Directions for Use for detailed instructions regarding the implantation and use of the 
WATCHMAN technology. The following will be assessed during implant procedure and 
documented on case report forms for enrolled subjects: 
• WATCHMAN Device and Access System usage information, including device 
size and compression post-implant; 
• LAA imaging (as described in section 11.4): LAA measurements; intracardiac 
thrombus, device position, LAA seal, thrombus on the device surface;  
• Concomitant procedures;  
• Current medical status; vital signs; AF status; 
• Current medication regimen for the use of antiplatelet and anticoagulation 
medications; 
• Serious adverse events and adverse events during implant procedure. Data to be 
collected for peri-procedural complications include, but are not limited to: 
 
o Cardiovascular events: pericardial effusion, cardiac tamponade, bleeding, 
stroke (ischemic/non-ischemic), TIA, systemic embolism (please refer to 
Appendix A for definitions of stroke/TIA and classification of bleeding 
events) 
o ICU : Length of stay 
o Conventional care unit: Length of stay 
o Device/procedure related complications 
11.6. Follow-up Procedures 
Subjects are expected to be followed at one post-implant visit (typically between 1-3 
months of implant), and then annually through 2 years post implant or until the study is 
terminated. An intermediate visit may be scheduled in a number of patients, per physician 
discretion. In order to reliably capture patient status at study end a FU window of 24 ± 3 
months will be considered acceptable for scheduling the last visit. For subjects who are 
not scheduled to visit the clinic for a follow-up, a subject contact (e.g. phone call) will 
ensure capture of the endpoint related information, however it is recommended to perform 
an office visit for at least the first annual visit. 
i) In-Hospital Visit 
The following will be assessed during each in-hospital visit and documented on case 
report forms for enrolled subjects: 
• Current medication regimen for the use of antiplatelet and anticoagulation 
medications; 
• Procedures performed since last visit; 

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• Current medical status; vital signs; AF status; 
• LAA imaging (as described in section 11.4): device position, LAA seal, thrombus 
on the device surface, intracardiac thrombus and residual atrial septal shunt;  
• Serious adverse events and adverse events experienced since last visit. Data to be 
collected include, but are not limited to (please refer to Appendix A for definitions 
of stroke/TIA and classification of bleeding events): 
 
o ER admission due to WATCHMAN implant related clinical events 
(stroke/TIA (ischemic/non-ischemic), systemic embolism, major and 
minor bleeding) 
o Hospitalization (ICU and Ward) due to WATCHMAN implant related 
clinical events (stroke/TIA (ischemic/non-ischemic), systemic embolism, 
major and minor bleeding) 
o Specialist visits due to WATCHMAN implant related clinical events 
(stroke/TIA (ischemic/non-ischemic), systemic embolism, major and 
minor bleeding) 
o Diagnostic procedure following a clinical event related to WATCHMAN  
(stroke/TIA (ischemic/non-ischemic), systemic embolism, major and 
minor bleeding) 
ii) Subject Contact 
For subjects who are not scheduled to visit the clinic for a follow-up, a subject contact 
(e.g. phone call) will ensure capture of the endpoint related information. The following 
will be assessed during each subject contact and documented on case report forms for 
enrolled subjects: 
• Current medication regimen for the use of antiplatelet and anticoagulation 
medications 
• Serious adverse events and adverse events experienced since last visit. Data to be 
collected include, but are not limited to (please refer to Appendix A for definitions 
of stroke/TIA and classification of bleeding events): 
 
o ER admission due to WATCHMAN implant related clinical events 
(stroke/TIA (ischemic/non-ischemic), systemic embolism, major and 
minor bleeding) 
o Hospitalization (ICU and Ward) due to WATCHMAN implant related 
clinical events (stroke/TIA (ischemic/non-ischemic), systemic embolism, 
major and minor bleeding) 
o Specialist visits due to WATCHMAN implant related clinical events 
(stroke/TIA (ischemic/non-ischemic), systemic embolism, major and 
minor bleeding) 

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o Diagnostic procedure following a clinical event related to WATCHMAN  
(stroke/TIA (ischemic/non-ischemic), systemic embolism, major and 
minor bleeding) 
11.7. Study Completion 
Each subject will be followed for 2 years after the implant. In order to reliably capture 
subject status at study end, FU assessment at 24 ± 3 months following implant will be 
considered acceptable. In case of premature termination of the study, data collection will 
stop accordingly. As this is an observational study, subjects will be managed according to 
standard of care as per centers practice following termination/completion of the study. 
11.8. 
Source Documents 
Printed, optical or electronic document containing source data shall be used; examples 
include hospital records, laboratory notes, device accountability records, radiographs, 
records kept at the investigation site, and at the laboratories involved in the clinical study. 
Where copies of the original source document as well as printouts of original electronic 
source documents are retained, these shall be signed and dated by a member of the 
investigation center team with a statement that it is a true reproduction of the original 
source document.  
12. Statistical Considerations 
An overview of the study design, sample size and statistical analysis is provided below.  
12.1. Sample Size Justification 
This is a prospective, multi-center non-randomized observational study with no formal 
pre-specified hypothesis test.  All subjects will be followed for up to 2 years or until the 
study is terminated.   
A sample size of up to 1000 subjects was chosen to assess incidence of rare events with a 
large degree of precision.  Table 3 provides the two-sided 95% confidence interval width 
assuming an event rate of 5%. 
 
Table 3: Two-Sided Confidence Interval by Sample Size 
 
Sample Size 
95% CI  
500 
5% ± 1.9% 
750 
5% ± 1.6% 
1000 
5% ± 1.4% 

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12.2. Statistical Analysis 
Analysis will include all subjects enrolled into the study who undergo an attempted 
implant of the WATCHMAN device. While no formal hypothesis tests will be performed, 
descriptive statistics will be generated for the data collected at baseline, during the 
implant procedure and at follow-up.  For continuous variables, the mean, standard 
deviation, median, range and 95% confidence intervals will be reported.  Confidence 
intervals (95%) for the difference between means will be used to compare groups.  For 
proportions, 95% confidence intervals will be reported.  For time-to-event analyses, all 
subjects not having an event or lost to follow-up will be censored at the time of the last 
documented follow-up visit.  Analyses may include, but will not be limited to, the 
following: procedural success, procedural complications, and incidence stroke/TIA. 
A variety of methods may be utilized in order to assess associations between the 
likelihood of each of the three outcomes and the patient and procedural characteristics 
outlined below.  Covariates will be chosen for inclusion in the models based on the 
number of patients with complete data for each outcome according to the prioritization in 
Table 4: Covariates of Interest. 
 
Methods to model multivariate associations may include but are not limited to the 
following: 
o Univariate analysis of individual predictors, and subsequent construction of 
multivariate logistic regression models incorporating all significant 
univariate predictors. 
o Parsimonious multivariate logistic regression models constructed through 
stepwise selection algorithm. 
o Classification and regression tree models.   
 
 
 
 
 
Table 4: Covariates of Interest 
• Age  80 years 
• Gender 
• Type of AF (paroxysmal; persistent; permanent) 
• Previous Stroke/TIA 
• Previous major bleeding event 
• HASBLED  3 
• CHADS2  3 

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• CHA2DS2-VASc  5 
• Type of anticoagulation therapy (Warfarin; NOACs; antiplatelet) 
• Multiple concomitant procedures vs watchman implant only 
 
13. Data Management 
13.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by Medidata. All changes 
made to the clinical data will be captured in an electronic audit trail and available for 
review by Boston Scientific Corporation (BSC) or its representative. The associated 
RAVE software and database have been designed to meet regulatory compliance for 
deployment as part of a validated system compliant with laws and regulations applicable 
to the conduct of clinical studies pertaining to the use of electronic records and signatures. 
Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on 
printouts of the eCRFs must also be provided if required by local regulation. Changes to 
data previously submitted to the sponsor require a new electronic signature by the 
Investigator acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the EDC system and 
will be issued to the site for appropriate response. Site staff will be responsible for 
resolving all queries in the database in a timely manner. 
13.2. Data Retention 
The Investigator will maintain, at the investigative site, in original format all essential 
study documents and source documentation that support the data collected on the study 
subjects in compliance with ICH/GCP guidelines.  Documents must be retained for at 
least 2 years after the last approval of a marketing application or until at least 2 years have 
elapsed since the formal discontinuation study. These documents will be retained for a 
longer period of time by agreement with BSC or in compliance with other local 
regulations. It is BSC’s responsibility to inform the Investigator when these documents no 
longer need to be maintained. The Investigator will take measures to ensure that these 
essential documents are not accidentally damaged or destroyed. If for any reason the 
Investigator withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change.  

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14. Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject 
or scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., 
IRB/EC/FDA/CA) of the revised protocol must be obtained prior to implementation. 
15. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to 
protect the life and physical well-being of a subject in an emergency. An investigator 
shall notify the sponsor and the reviewing IRB/EC of any deviation from the 
investigational plan to protect the life or physical well-being of a subject in an emergency, 
and those deviations which affect the scientific integrity of the clinical investigation.  
All deviations from the investigational plan, with the reason for the deviation and the date 
of occurrence, must be documented and reported to the sponsor within 14 days using the 
appropriate EDC eCRF. Sites may also be required to report deviations to the IRB/EC, 
per local guidelines and government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, 
appropriate corrective and preventive actions (including notification, center re-training, or 
discontinuation) will be put into place by the sponsor or its representatives. 
16. Compliance 
16.1. Statement of Compliance 
This study will be conducted in accordance with ISO 14155:2011 Clinical Investigation 
of Medical Devices for Human Subjects-Good Clinical Practice, or the relevant parts of 
the ICH Guidelines for Good Clinical Practice, ethical principles that have their origins in 
the Declaration of Helsinki, and pertinent individual country laws and regulations. The 
study shall not begin until the required approval/favorable opinion from the Ethics 
Committee and/or regulatory authority has been obtained, if appropriate. Any additional 
requirements imposed by the EC or regulatory authority shall be followed, if appropriate. 
16.2. Investigator Responsibilities 
The Principal Investigator of an investigational center is responsible for ensuring that the 
study is conducted in accordance with the Clinical Study Agreement, the investigational 
plan/protocol, ISO 14155, ethical principles that have their origins in the Declaration of 
Helsinki, any conditions of approval imposed by the reviewing IRB/EC, and prevailing 
local and/or country laws and/or regulations, whichever affords the greater protection to 
the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  

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• Prior to beginning the study, sign the Investigator Agreement and Protocol Signature 
page documenting his/her agreement to conduct the study in accordance with the 
protocol. 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the center team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study 
or interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and 
physical well-being of a subject in an emergency; document and explain any deviation 
from the approved protocol that occurred during the course of the clinical 
investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all 
clinical-investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to 
the sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) 
every adverse event and observed device deficiency. 
• Report to BSC, per the protocol requirements, all SAEs and device deficiencies that 
could have led to a SADE. 
• Report to the IRB/EC and regulatory authorities any SAEs and device deficiencies 
that could have led to a SADE, if required by the national regulations or this protocol 
or by the IRB/EC, and supply BSC with any additional requested information related 
to the safety reporting of a particular event. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to 
the monitor and respond to questions during monitoring visits. 
• Allow and support regulatory authorities and the IRB/EC when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/EC requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in 
a clinical study in the case of adverse events, as described in the Informed Consent 
Form (ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 

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• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, Ensure that clinical medical records are clearly marked to indicate that the 
subject is enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together 
with identification and compliance information for concomitant treatment measures 
(contact address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical 
investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained 
and documented during the clinical investigation. 
• Ensure that maintenance and calibration of the equipment relevant for the assessment 
of the clinical investigation is appropriately performed and documented, where 
applicable. 
16.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, included but not limited to 
conducting the informed consent process, the investigator is responsible for providing 
appropriate training and adequate supervision of those to whom tasks are delegated. The 
investigator is accountable for regulatory violations resulting from failure to adequately 
supervise the conduct of the clinical study.  
16.2.2. Investigator Records 
The investigator is responsible for the preparation (review and signature) and retention of 
the records cited below.  Records are subject to inspection and must be retained for a 
period of at least two (2) years (or according to local regulatory requirements) after the 
investigation is terminated or the date that the records are no longer required for purposes 
of supporting publications or regulatory submissions. 
• All significant correspondence which pertains to the investigation 
• Subjects’ case history records, including: signed subject informed consent form; 
all relevant observations; observations of adverse device events; medical history; 
completed sponsor Case Report Forms; documentation of the dates and reasons 
for any deviation from the protocol  
• Copies of Case Report Forms and clinical data 

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• Signed Investigator Agreement and recent curriculum vitae, both of which also 
must be submitted to the sponsor 
• IRB/EC approval and discourse documentation.  A copy of the IRB/EC approval 
must be submitted to the sponsor 
16.3. Institutional Review Board/ Ethics Committee 
A copy of the protocol, proposed Informed Consent form, other written subject 
information, and any proposed advertising material must be submitted to the EC for 
written approval.  A copy of the written EC approval of the protocol and Informed 
Consent form must be received by the sponsor before recruitment of subjects into the 
study and shipment of investigational product. 
The Investigator must submit and, where necessary, obtain approval from the EC for all 
subsequent protocol amendments and changes to the Informed Consent form.  The 
Investigator must notify the EC of deviations from the protocol or SAEs and SADEs 
occurring at the site in accordance with local procedures. 
The Investigator is responsible for obtaining annual EC approval and renewal throughout 
the duration of the study.  Copies of the Investigator’s reports and the EC continuance of 
approval must be sent to the sponsor. 
16.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this 
study will be considered confidential by BSC. Only authorized BSC personnel or a BSC 
representative will have access to these confidential records. Authorized regulatory 
personnel have the right to inspect and copy all records pertinent to this study. Study data 
collected during this study may be used by BSC for the purposes of this study, 
publication, and to support future research and/or other business purposes. All data used 
in the analysis and reporting of this study will be without identifiable reference to specific 
subject name. 
Boston Scientific will keep subjects’ health information confidential in accordance with 
all applicable laws and regulations.  Boston Scientific may use subjects’ health 
information to conduct this study, as well as for additional purposes, such as overseeing 
and improving the performance of its device, new medical research and proposals for 
developing new medical products or procedures, and other business purposes. 
Information received during the study will not be used to market to subjects; subject 
names will not be placed on any mailing lists or sold to anyone for marketing purposes.  
16.4.1. Sponsor Records 
The sponsor will maintain the following records: 
• All correspondence which pertains to the investigation 

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• Signed investigator agreements and curriculum vitae 
• System/procedure related Adverse Device Events  
• All case report forms, including samples of subject informed consents, submitted 
by the investigator; investigational plan and report of prior investigations 
• Hospital staff training and study visit reports 
• The sponsor will own and store the clinical data generated under this protocol 
16.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by 
BSC for subjects in the study will be obtained. 
17. Monitoring 
Monitoring (on-site and remote) will be performed during the study to assess continued 
compliance with the protocol and applicable regulations. In addition, the monitor verifies 
that study records are adequately maintained, that data are reported in a satisfactory 
manner with respect to timeliness, adequacy, and accuracy, and that the Investigator 
continues to have sufficient staff and facilities to conduct the study safely and effectively. 
The Investigator/institution guarantees direct access to original or electronic source 
documents by BSC personnel, their designees, and appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by BSC or its designees, as 
well as inspection by appropriate regulatory authorities. It is important that the 
Investigator and relevant study personnel are available during on-site monitoring visits or 
audits and that sufficient time is devoted to the process. 
 
18. Potential Risks and Benefits 
18.1. Risks Associated with the study 
Patients enrolled in this study will not be exposed to any additional testing, visits or risks 
as compared to patients who are routinely implanted with the WATCHMAN device and 
not enrolled in this study. The study only collects data from procedures and visits that are 
performed as routine practice, based on the patient’s clinical indications  
18.2.  Risks Associated with a standard WATCHMAN Implant & Procedure 
Even if the WATCHMAN implant is performed as part of clinical practice, for 
completeness of information we report here the section of the WATCHMAN Directions 
For Use listing the possible adverse events and possible adverse device effects associated 
with implantation of a WATCHMAN device, in alphabetical order: 

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1. •         Air Embolism 
2. •         Allergic Reaction to Contrast Media/Meds 
 •         Anemia Requiring Transfusion
1. •         Arrhythmias 
•         AV Fistula
2. •         Bruising - Hematoma 
 •         Cranial Bleed
•         Death
1. •         Device Embolization 
2. •         Device Thrombus 
•         Excessive Bleeding
•         Gastrointestinal Bleeding
3. •         Groin Puncture Bleed 
1. •         Hypotension 
1. •         Inability to Move or Retrieve Device 
2. •         Infection/Pneumonia 
1. 
         Major Bleed Requiring Transfusion 
 •         Pericardial Effusion
1. •         Pleural Effusion 
•         Post Procedure Anesthesia Effects
•         Pseudoaneurysm
2. •         Pulmonary Edema 
•         Stroke - Hemorrhagic
1. •         Stroke - Ischemic 
•         Systemic Embolism
2. •         TEE Complications (throat pain, bleeding) 
•         Thrombosis
•         Thrombus at Septal Puncture
3. •         Transient Ischemic Attack (TIA) 
•         Vasovagal Reactions
 
Some additional events that may be expected in catheterization procedures include: 
• Pneumothorax 
• Pulmonary Vein Obstruction 

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• Valvular or vascular damage 
18.3. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this 
protocol, performing procedures in the appropriate hospital environment, adherence to 
subject selection criteria, close monitoring of the subject's physiologic status during 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent 
information required by this protocol. 
18.4. Anticipated Benefits 
No direct patient benefit is expected from this study. Patients enrolled in this study will 
receive the same clinical care as patients who are routinely implanted with WATCHMAN 
and not enrolled in this study. However, results from the data collected during this study 
may improve the management of WATCHMAN patients in the future, therefore the 
subjects enrolled in this study may also benefit at a later stage.  
The potential benefit of implanting the WATCHMAN device is its expected ability to 
prevent thromboembolic events originating in the LAA. The WATCHMAN device may 
protect against ischemic stroke and systemic thromboembolism.  In subjects implanted 
with the device, the elimination of Warfarin therapy may reduce bleeding complications, 
such as hemorrhagic stroke, associated with long-term anticoagulation.  
19. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required 
from all subjects or their legally authorized representative. The Investigator is responsible 
for ensuring that Informed Consent is obtained prior to any procedures and/or testing, or 
data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, 
and local Ethics Committee and/or Regulatory authority body, as applicable. The ICF 
must be approved by the center’s IRB, or central IRB, if applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of 
the investigative center’s EC and local regulations. Any modification requires approval 
from BSC, or its representative, prior to use of the form.  The ICF must be in a language 
understandable to the subject and if needed, BSC will assist the center in obtaining a 
written consent translation. Translated consent forms must also have EC approval prior to 
their use.  Privacy language shall be included in the body of the form or as a separate 
form as applicable.   
The process of obtaining Informed Consent shall: 

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• be conducted by the Principal Investigator or designee authorized to conduct the 
process,  
• include a description of all aspects of the clinical study that are relevant to the 
subject’s decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects throughout 
the clinical study. 
The ICF shall always be signed and personally dated by the subject or legal representative 
and by the investigator or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide 
informed consent for continued participation as soon as his/her medical condition allows. 
The original signed ICF will be retained by the center and a copy of the signed and dated 
document and any other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
body according to their requirements (e.g., FDA requirement is within 5 working days of 
learning of such an event). Any violations of the informed consent process must be 
reported as deviations to the sponsor and local regulatory authorities, as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written 
form via a revised ICF or, in some situations, enrolled subjects may be requested to sign 
and date an addendum to the ICF. In addition to new significant information during the 
course of a study, other situations may necessitate revision of the ICF, such as if there are 
amendments to the protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB. The new version of the ICF must be approved by the 
IRB/EC. Boston Scientific approval is required if changes to the revised ICF are 
requested by the center’s IRB/EC. The IRB/EC will determine the subject population to 
be re-consented. 
 
 
 
 

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20. Safety Reporting 
Adverse event definitions are provided in Table 5.  
 
Table 5: Adverse Event Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 12/2010 
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the 
investigational medical device.  
NOTE 1: This includes events related to the investigational medical 
device or comparator. 
NOTE 2: This definition includes events related to the procedures 
involved (any procedure in the clinical investigation plan). 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 12/2010 
Adverse event related to the use of an investigational medical device 
NOTE 1: This definition includes any adverse event resulting from 
insufficient or inadequate instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
from intentional misuse of the investigational medical device. 
 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 12/2010 
Adverse event that: 
o 
Led to death, 
o 
Led to serious deterioration in the health of the subject, 
that either resulted in: 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function, or 
o in-patient or prolonged hospitalization of existing hospitalization, 
or 
o medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
o 
Led to fetal distress, fetal death, or a congenital 
abnormality or birth defect. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 12/2010 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 

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Table 5: Adverse Event Definitions 
Term 
Definition 
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 12/2010 
 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the System 
Guide of each device model 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in 
the current version of the System Guide of each device model 
Device Deficiency 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 12/2010 
A device deficiency is any inadequacy of a medical device with respect to 
its identity, quality, durability, reliability, safety or performance. 
NOTE 1: Device deficiencies include malfunctions, misuse or use errors, 
and inadequate labeling. 
 
Abbreviations: EC=Ethics Committee; IRB=Institutional Review Board 
 
20.1. Investigator Reporting Requirements 
When reporting an Adverse Event the investigator will indicate the diagnosis of the event 
and correlating signs and symptoms on the adverse event case report form.  Individual 
signs and symptoms and treatment/intervention/diagnostic testing should not be reported 
as separate adverse events, instead be reported as supporting documentation on the AE 
CRF.  Additionally, it is not necessary to report an underlying disease that was present at 
baseline (i.e., CHF, AF, hypertension, chronic anemia, etc.).  However, any increase in 
the severity of the underlying disease may require reporting, if at the determination of the 
investigator, it is relevant to the study. If possible, death should not be recorded as an AE, 
but should only be reflected as an outcome of a specific SAE (see Table 5 for AE 
definitions).  
Adverse experiences that require reporting by the investigator to the sponsor include any 
adverse event with clinical symptoms that could possibly be contributed to any of the 
following: 
4. The WATCHMAN device; 
5. The WATCHMAN implant procedure; 
6. The use of medications including warfarin, or other equivalent oral anticoagulant 
per institution’s protocol, clopidogrel or aspirin (i.e., gastrointestinal bleeding due 
to warfarin or an allergic reaction to clopidogrel); 
7. Any WATCHMAN related procedures (i.e., clinical complications from TEE or 
other procedure required by labeling) 
The following adverse events will also be reported: 
8. Neurological events including, but not limited to, stroke, TIA or seizure which are 
not pre-study conditions 
9. Any events possibly related to stroke/TIA, systemic embolization, death, etc.  

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10. Thrombosis   
11. Bleeding complications requiring intervention or transfusion of blood.  
Please refer to Appendix A for definitions of stroke/TIA and classification of bleeding 
events. Each adverse event will be evaluated by the investigator for relatedness and 
seriousness.   
The communication requirements for reporting to BSC are as shown in Table 6: 
Table 6: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline  
Unanticipated Serious Adverse 
Device Effect  
 
Complete AE eCRF page 
with all available new and 
updated information 
o 
Within 1 business day of 
first becoming aware of 
the event. 
o 
Terminating at the end of 
the study 
Serious Adverse Event 
including Serious Adverse 
Device Effects 
Complete AE eCRF page 
with all available new and 
updated information 
o 
Within 2 business days of 
first becoming aware of 
the event or as per 
local/regional regulations. 
o 
Reporting required 
through the end of the 
study 
Provide all relevant source 
documentation 
(unidentified) for reported 
event 
o 
When documentation is 
available 
Adverse Event 
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE 
resolution, assessment of 
seriousness and 
relationship to the device 
o 
No later than 14 working 
days after becoming 
aware of the information 
o 
Reporting required 
through the last visit of 
the patient in the study, 
with the exception of 
following up open 
adverse events until 
resolved or considered 
stable.  
Device Deficiencies (including 
but not limited to failures, 
malfunctions, and product 
nonconformities) 
Note: Any Investigational 
Device Deficiency that might 
have led to a serious adverse 
event if a) suitable action had 
not been taken or b) 
intervention had not been made 
or c) if circumstances had been 
Complete applicable 
Device Deficiency CRF 
page with all available 
new and updated 
information 
o 
Investigators should 
report within 14 business 
days of first becoming 
aware of the event and as 
per local/regional 
regulations 
o 
Reporting required 
through the end of the 
study 

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Table 6: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline  
less fortunate is considered a 
reportable event. 
Abbreviations: AE=adverse event; CRF=case report form; IDE=Investigational Device Exemption; 
UADE=unanticipated adverse device effect 
 
20.2. Boston Scientific Device Deficiencies 
All device deficiencies will be documented and reported to BSC on the appropriate eCRF 
within 14 business days of first becoming aware of the event.  Device deficiencies are not 
to be reported as adverse events. However, if there is an adverse event that results from a 
device deficiency, that specific event would be recorded on the appropriate eCRF.  If 
possible, the device(s) should be returned to BSC for analysis. If it is not possible to 
return the device, the investigator should document why the device was not returned and 
the final disposition of the device. Device deficiencies should also be documented in the 
subject’s medical record. 
20.3. Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating 
investigators and regulatory authorities, as applicable. The Principal Investigator is 
responsible for informing the IRB/EC, and regulatory authorities of UADE and SAE as 
per local/regional requirements. 
21. Committees 
21.1. Safety Monitoring Process 
The BSC Medical Safety group will provide safety oversight and classify individual 
events. During regularly scheduled monitoring visits, clinical research monitors will 
support the dynamic reporting process through their review of source document 
information. 
The BSC Medical Safety group includes physicians with expertise in Electrophysiology 
(EP), and/ or Cardiology, as well as other healthcare professionals with the necessary 
therapeutic and subject matter expertise to evaluate and classify the events into the 
categories outlined above 
21.2. Executive/Steering Committee 
An Executive Committee composed of the sponsor's Clinical Management and the study 
Coordinating Principal Investigator(s) may be convened. Responsibilities may include 
oversight of the overall conduct of the study with regard to protocol development, study 

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progress, subject safety, overall data quality and integrity, and first line review and final 
decision making of independent medical reviewer recommendations, as well as 
disseminating any study results through appropriate scientific sessions and publications. 
Executive Committee members may participate in the review and approval of all requests 
for data analysis, abstract and manuscript preparation, and submission. As appropriate, 
the Executive Committee may request participation of WATCHMAN Registry 
Investigators on the Committee. 
22. Suspension or Termination 
This study may be terminated at any time. Upon completion or termination, all data must 
be returned to the sponsor. 
23. Publication Policy 
The results of this study may be submitted in the form of abstracts to international and/or 
national congresses and/or in the form of publications to scientific journals. Publication 
policy will be, at a minimum, dependent on the number of complete patient datasets per 
site. Boston Scientific is committed to supporting publication of results of Boston 
Scientific-sponsored clinical research investigations in written or oral publications. 
Boston Scientific shall do its best to support proposals for sub-analysis and to include as 
many participating investigators despite the fact that authorship cannot be guaranteed. 
Therefore clinical investigators are encouraged to identify topics of interest and initiate 
publications on their own or the pooled data. This will be done in close cooperation with 
the Sponsor and with the International Study Chairman or/and an Executive committee, if 
any has been defined. No abstract(s) or article(s) can be submitted for publication without 
prior authorization from the Sponsor. In accordance with the Corporate Policy on the 
Conduct of Human Subject Research, Boston Scientific requires disclosure of its 
involvement as a sponsor or financial supporter in any publication or presentation relating 
to a Boston Scientific study or its results. In accordance with the Corporate Policy for the 
Conduct of Human Subject Research, Boston Scientific will submit study results for 
publication (regardless of study outcome) following the conclusion or termination of the 
study. Boston Scientific Corporation adheres to the Contributorship Criteria set forth in 
the Uniform Requirements of the International Committee of Medical Journal Editors 
(ICMJE; http://www.icmje.org). In order to ensure the public disclosure of study results 
in a timely manner, while maintaining an unbiased presentation of study outcomes, 
Boston Scientific personnel may assist authors and investigators in publication 
preparation provided the following guidelines are followed. 
• All authorship and contributorship requirements as described above must be 
followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy 
should be discussed with the Coordinating Principal Investigator(s) and/or 
Executive/Steering Committee at the onset of the project. 

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• The First and Senior authors are the primary drivers of decisions regarding 
publication content, review, approval, and submission.  
 
 

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24. Bibliography 
1. 
Hankey GJ. Non-valvular atrial fibrillation and stroke prevention. National blood 
pressure advisory committee of the national heart foundation. Med J Aust. 2001;174:234-
239 
2. 
Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin 
JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, 
Smith SC, Jr., Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura 
R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, 
Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, 
Osterspey A, Zamorano JL. Acc/aha/esc 2006 guidelines for the management of patients 
with atrial fibrillation--executive summary: A report of the american college of 
cardiology/american heart association task force on practice guidelines and the european 
society of cardiology committee for practice guidelines (writing committee to revise the 
2001 guidelines for the management of patients with atrial fibrillation). J Am Coll 
Cardiol. 2006;48:854-906 
3. 
Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW. Factors associated 
with ischemic stroke during aspirin therapy in atrial fibrillation: Analysis of 2012 
participants in the spaf i-iii clinical trials. The stroke prevention in atrial fibrillation (spaf) 
investigators. Stroke. 1999;30:1223-1229 
4. 
White HD, Gruber M, Feyzi J, Kaatz S, Tse HF, Husted S, Albers GW. 
Comparison of outcomes among patients randomized to warfarin therapy according to 
anticoagulant control: Results from sportif iii and v. Arch Intern Med. 2007;167:239-245 
5. 
Connolly SJ, Pogue J, Eikelboom J, Flaker G, Commerford P, Franzosi MG, 
Healey JS, Yusuf S. Benefit of oral anticoagulant over antiplatelet therapy in atrial 
fibrillation depends on the quality of international normalized ratio control achieved by 
centers and countries as measured by time in therapeutic range. Circulation. 
2008;118:2029-2037 
6. 
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue 
J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis 
BS, Darius H, Diener HC, Joyner CD, Wallentin L. Dabigatran versus warfarin in patients 
with atrial fibrillation. N Engl J Med. 2009;361:1139-1151 
7. 
Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L. Newly identified 
events in the re-ly trial. N Engl J Med. 2010;363:1875-1876 
8. 
Hart RG, Diener HC, Yang S, Connolly SJ, Wallentin L, Reilly PA, Ezekowitz 
MD, Yusuf S. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation 
with warfarin or dabigatran: The re-ly trial. Stroke. 2012;43:1511-1517 
9. 
FDA Drug Safety Communication: Update on the risk for serious bleeding events 
with 
the 
anticoagulant 
Pradaxa 
(dabigatran) 
FDSC. 
http://www.fda.gov/Drugs/DrugSafety/ucm326580.htm.  
10. 
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, 
Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, 
Fox KA, Califf RM. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl 
J Med. 2011;365:883-891 

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11. 
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-
Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, 
Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, 
Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, 
Parkhomenko A, Verheugt FW, Zhu J, Wallentin L. Apixaban versus warfarin in patients 
with atrial fibrillation. N Engl J Med. 2011;365:981-992 
12. 
Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Halperin JL, 
Holmes D. Percutaneous left atrial appendage closure for stroke prophylaxis in patients 
with atrial fibrillation: 2.3-year follow-up of the protect af (watchman left atrial 
appendage system for embolic protection in patients with atrial fibrillation) trial. 
Circulation. 2013;127:720-729 
13. 
Rhythm H. The heart rhythm society’s 34th annual scientific sessions. 2013  
14. 
Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left 
atrial appendage closure: Results from the watchman left atrial appendage system for 
embolic protection in patients with af (protect af) clinical trial and the continued access 
registry. Circulation. 2011;123:417-424 
 
 
 

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Appendix A - Definitions 
A.1 Stroke/TIA definitions 
Broad definitions: 
Transient ischemic attack: An episode of acute neurological dysfunction presumed to 
be caused by transient ischemia, with rapid symptom resolution (usually 1–2 h), 
resolving completely within 24 hours. Neuroimaging without tissue injury. 
Stroke: An episode of acute neurological dysfunction presumed to be caused by 
ischemia or hemorrhage, persisting ≥24 hours or until death; preferably with positive 
neuroimaging study;  
 
Stroke diagnostic criteria:  
Rapid onset of a focal or global neurological deficit with at least one of the following: 
change in level of consciousness, hemiplegia, hemiparesis, numbness or sensory loss 
affecting one side of the body, dysphasia or aphasia, haemianopia, amaurosis fugax, or 
other neurological signs or symptoms consistent with stroke;  
Duration of a focal or global neurological deficit ≥24 h; OR , 24 h, if therapeutic 
intervention(s) were performed (e.g. thrombolytic therapy or intracranial angioplasty); 
OR available neuroimaging documents a new haemorrhage or infarct; OR the 
neurological deficit results in death  
No other readily identifiable non-stroke cause for the clinical presentation (e.g. brain 
tumour, trauma, infection, hypoglycaemia, peripheral lesion, pharmacological 
influences) 
Confirmation of the diagnosis by at least one of the following: 
Neurology or neurosurgical specialist 
Neuroimaging procedure (MR or CT scan or cerebral angiography) 
Lumbar puncture (i.e. spinal fluid analysis diagnostic of intracranial haemorrhage) 
 
 (from From Leon MB, Eur Heart J. 2011 Jan;32(2):205-17) 
 
 
A.2 Classification of Bleeding events 
In response to the need to develop, disseminate, and ultimately adopt standardized 
bleeding end-point definitions for patients receiving antithrombotic therapy, the Bleeding 
Academic Research Consortium (BARC) convened in February 2010 at the US Food and 
Drug Administration (FDA) headquarters in White Oak, MD. BARC effort brought 
together representatives from academic research organizations, the FDA, the National 
Institutes of Health, and pharmaceutical and cardiovascular device manufacturers and 
independent physician thought leaders in the field of cardiovascular disease to develop 
consensus bleeding definitions that would be useful for cardiovascular clinical trials. 
Application of these definitions is recommended for both clinical trials and registries:  
 

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Type 0: 
No bleeding 
Type 1: 
Bleeding that is not actionable and does not cause the patient to seek unscheduled 
performance of studies, hospitalization, or treatment by a health-care professional; may 
include episodes leading to self-discontinuation of medical therapy by the patient without 
consulting a health-care professional. 
Type 2: 
Any overt, actionable sign of hemorrhage (e.g., more bleeding than would be expected for a 
clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria 
for type 3, 4, or 5 but does meet at least one of the following criteria: 
1. requiring nonsurgical, medical intervention by a health-care professional, 
2. leading to hospitalization or increased level of care, or 
3. prompting evaluation 
Type 3: 
Type 3a: 
1. Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL* (provided hemoglobin drop is 
related to bleed) 
2. Any transfusion with overt bleeding 
Type 3b: 
1. Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided hemoglobin drop is related to 
bleed), 
2. Cardiac tamponade, 
3. Bleeding requiring surgical intervention for control (excluding 
dental/nasal/skin/haemorrhoid), 
4. Bleeding requiring intravenous vasoactive agents 
Type 3c: 
1. Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, 
does include intraspinal), 
2. Subcategories confirmed by autopsy or imaging or lumbar puncture, 
3. Intraocular bleed compromising vision. 
Type 4: 
1. CABG-related bleeding, 
2. Perioperative intracranial bleeding within 48 h, 
3. Reoperation after closure of sternotomy for the purpose of controlling bleeding 
4. Transfusion of ≥ 5 U whole blood or packed red blood cells within a 48-h period, 
5. Chest tube output more than or equal to 2L within a 24-h period 
Type 5: 
Fatal bleeding 
Type 5a: 
Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious 
Type 5b: 
Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation 
 
(from Circulation. 2011; 123(23): 2736-47)