Efficacy of Short Term Dabigatran Etexilate Followed by Aspirin Monotherapy After LAA (Left Atrial Appendage) Device Closure (the DEA-LAA Study).

Single arm, prospective unblinded study on post Watchman LAA closure device implant
anti-coagulation management at a primary center (Vanderbilt Medical Center) and up to 5
additional high volume LAA implant centers. This trial will be designed to evaluate the use
of dabigatran for 90 days post implantation of an LAA closure device (Watchman LAA Closure
Device, Boston Scientific Inc.).

The drug will be initiated on the morning following device implantation, taken BID per
package insert dosing and until follow-up 90-day post implant TEE. Aspirin monotherapy will
be utilized in conjunction at 81 mg for up to 12 months, after which the patients will be
exited from the study and further treatment decisions will be made by the following physician
(see Schedule of Study Procedures at end of protocol). The objective of this trial is to
evaluate safety and efficacy of a 90-day period of dabigatran etexilate following LAA closure
to prevent device associated thrombus, while minimizing adverse bleeding by eliminating the
need for clopidogrel.

This is a single arm pilot study with the option (pending collaboration with additional
funding source) to expand to a full single arm non-inferiority trial design with 80% power to
detect a 1.4% difference with the non-inferiority margin 1% in absolute rate of DAT (control
rate 3.9%).

Prospective, non-randomized single arm study. Comparison will be made to historical controls
based on published one year DAT rates from PROTECT-AF, PREVAIL clinical trials, and
EWOLUTION, and ACP/Amulet registries.

Echocardiography (TEE) will be performed at 90 days (3 months, +/- 2-week window), and again
at 1-year post implant (+/- 4 weeks). Selected images will be interpreted by echo lab at
coordinating center in an anonymous fashion (patient data de-identified). Ideal imaging will
incorporate 0, 45, 90 and 135 degree angled views on the device at follow up.

Drug will be dispensed as part of the clinical trial supplied from the sponsor and each
patient will receive a complete 90 days' supply up front. They will have a drug visit on the
day of TEE with the research coordinator to hand back any remaining dabigatran, with clear
instruction to stop the drug and only take ASA following confirmation of closure on TEE (no
peri-device leak on Doppler of >5mm). A decision to continue anti-coagulation post closure
90day TEE will be made by the physician discretion based on TEE findings. If thrombus is
found at the 90 days TEE, anti-coagulation may be extended another 6 weeks with repeat TEE
imaging to confirm clot resolution at the discretion of the investigator. In the unlikely
event of embolization or Doppler leak >5mm, decision on extending anti-coagulation, or
re-implanting a device will be made by the following physician.

Additional baseline data collection: Patient demographics, medical history, age, sex, and
prior use of anti-coagulants or anti-platelet medications will be collected. CHADS 2 Vasc,
and HAS-BLED score calculated. Main indication for LAA closure must be documented. Baseline
CBC and BMP required on day of implant or up to 1 week pre-procedure (typical standard of
care labs at time of implant). This will include a recent calculation of Creatinine Clearance
(using Cockroft Gault and using patients actual body weight) and dosing of study drug will be
made in accordance (see below). Repeat PCV or hematocrit on the morning after Watchman LAAC
implantation will be per hospital standard. PCV or hematocrit value pre-implant and at the
post 90-day visit will be analyzed.

Calculation for dabigatran dosing:

CCr={ (l40-age) x weight in kg)/(72 x SCr) } x 0.85 (if female)

Implant procedure variables to collect include access site, sheath used for deployment (WAS),
device size at implant and number of implant attempts. LA pressure mean if available.
Presence of angiography contrast or Doppler Echo leak, thrombus, or pericardial effusion post
implant will be recorded. At 90 days, TEE report findings and image review (standard of care)
with drug dosing visit with research coordinator and return of any remaining study drug.

1 year TEE (standard of care) with a research exit visit with MD, physician extender, or
research coordinator, with documentation of ASA tolerance, dosing, and any late bleeding
episodes or hospitalizations (typically should be reported as AE/SAE when first knowledge of
event is determined). TEE images will be sent to the primary study site (Vanderbilt
University Medical Center) and core TEE lab will review to confirm presence or absence of
DAT. In cases of CTA utilized for follow up, similarly images will be reviewed by chest
radiology team at Vanderbilt.

Medication administration with 90 days of dabigatran to be dispensed by pharmacy ideally one
time (180 capsules).

Inclusion Criteria:

1. Male or female sex, age >18 years.

2. CHADS2 Vascular score of 3-9 and HAS BLED score 2 or higher meeting CMS coverage
criteria for Watchman LAA closure device implantation.

3. Able to give informed consent.

4. Life expectancy of > 1year in the judgment of the implanting physician and shared
decision-making physician.

Exclusion Criteria:

1. Unable to give informed consent

2. History of confirmed allergy to dabigatran etexilate

3. Active cerebral bleeding, or active non-cerebral bleeding requiring blood transfusions
(any absolute contra-indications to anti-coagulation).

4. History of intraocular, spinal, retroperitoneal or a traumatic intra-articular
bleeding unless the causative factor has been permanently eliminated or repaired (e.g.
by surgery)

5. Gastrointestinal (GI) haemorrhage within one month prior to screening, unless, in the
opinion of the Investigator, the cause has been permanently eliminated (e.g. by
surgery)

6. Major bleeding episode (reduction in the haemoglobin level of at least 2g/dL,
transfusion of at least two units of blood, or symptomatic bleeding in a critical area
or organ) including life-threatening bleeding episode (symptomatic intracranial
bleeding, bleeding with a decrease in the haemoglobin level of at least 5g/dL or
bleeding requiring transfusion of at least 4 units of blood or inotropic agents or
necessitating surgery) in one month prior to screening visit

7. Intolerance to dabigatran, if medication naïve, or other contra-indications as per the
USPI, including ESRD on hemodialysis or GFR < 15ml/min, or concomitant use of
rifampin.

8. History of non-compliance, inability to follow-up.

9. Pre-menopausal women (last menstruation ≤ 1 year prior to screening) who are not
surgically sterile.

10. Ischemic stroke or hemorrhagic stroke within 90 days of LAA placement.

11. Anatomy unsuitable for LAA closure (incomplete surgical LAA ligation without suitable
anatomy for Watchman placement. LAA ostial measurements >31mm, or <17mm in all views).

12. Requires long-term oral anticoagulation therapy for a condition other than atrial
fibrillation.

13. ASA allergy, or confirmed allergy to nickel.

14. Prior PFO or ASD closure device or prosthetic or mechanical heart valve.

15. Acute MI within 90 days.

16. Platelets <50,000 at time of Watchman LAAC implantation.

17. Active endocarditis.

18. Planning for endocardial catheter AF or left atrial ablation within 90 days of
Watchman implantation.