Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation

Prospective, Randomized Cohort

Subjects undergoing ablation for NVAF who meet all eligibility criteria and sign informed
consent will be enrolled into the study. Subjects will be treated with apixaban for ≥21 days
prior to the ablation procedure (for subjects already on apixaban for ≥21 days, it is not
necessary to wait 21 days before the ablation procedure. Apixaban dose will be 5 mg b.i.d.
per product label, or 2.5 mg b.i.d. in subjects with 2 or more of the following: age ≥80
years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.

Eligible subjects will then be randomized in a 1:1 ratio to 2 peri-procedural treatment
strategies:

- Uninterrupted treatment: administer the evening apixaban dose on the day prior to the
procedure; administer the morning apixaban dose on the day of the procedure; administer
heparin bolus before transseptal puncture to maintain a target activated clotting time
[ACT] > 300 seconds; administer the evening apixaban dose after the procedure if there
were no peri-procedural complications that necessitate withholding anticoagulation for
longer duration.

- Interrupted treatment: administer the evening apixaban dose on the day prior to the
procedure; do not administer the morning apixaban dose on the day of the procedure;
administer heparin bolus before transseptal puncture to maintain a target ACT > 300
seconds; administer the evening apixaban dose after the procedure if there were no
peri-procedural complications that necessitate withholding anticoagulation for longer
duration.

Randomization will take place prior to the procedure (on the day of the procedure or up to 3
days prior to the procedure) and will be stratified by site.

It is anticipated that up to 360 subjects may be enrolled in order to evaluate a total of
300 randomized subjects (150 subjects per treatment arm):

Randomized subjects will continue treatment with apixaban for 1 month post procedure.

Retrospective, Warfarin Cohort In addition, a chart review of 300 warfarin-treated patients
who underwent catheter ablation for NVAF on or after September 1, 2013 in the enrolling
centers and who have documented follow-up in the medical record for ≥ 30 days post-ablation
procedure will be performed. Patient records for warfarin-treated individuals who meet the
applicable inclusion/exclusion criteria and who are matched 1:1 to a subject in the
prospective, randomized cohort for age (+/- 5 years), gender and atrial fibrillation (AF)
type (paroxysmal vs. persistent), will be identified. Sites will document key demographic
and outcome variables. This review will be performed in a blinded manner such that site
personnel are blinded to the outcome of each retrospective subject during the subject
selection process. Only pre-existing data will be collected for the analysis of this cohort.

Inclusion Criteria:

1. Signed informed consent.

2. >18 years of age.

3. NVAF with planned catheter ablation treatment.

4. Planned anticoagulant treatment for at least 1 month after the index procedure.

5. Subject agrees to all required follow-up procedures and visits.

6. For women of childbearing potential (WOCBP):

- Must have a negative serum or urine pregnancy test within 24 hours prior to the
start of study drug.

- Must not be breastfeeding

- Must agree to follow instructions for method(s) of contraception for a total of
33 days post-treatment completion.

7. Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for a total of 93 days post-treatment completion.

8. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt
from contraceptive requirements. However, WOCBP must still undergo pregnancy testing
as described in this section.

Exclusion Criteria:

1. History of significant bleeding diathesis or coagulopathy or inability to accept
blood transfusions.

2. Known hypersensitivity or contraindication to heparin or apixaban.

3. Subjects with mechanical prosthetic heart valves.

4. History of cerebrovascular accident or transient ischemic attach (TIA) within the
last 6 months.

5. Prior intracranial hemorrhage.

6. End-stage renal failure (creatinine clearance rate <15 mL/minute or on dialysis
treatment).

7. Hepatic disease associated with coagulopathy.

8. Current or expected systemic treatment with strong dual inducers of CYP3A4 and
P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort).

9. Current or expected systemic treatment with dual antiplatelet therapy, other
anticoagulants, or fibrinolytics.

10. Planned or expected surgery, or other invasive procedure that would require
interruption of anticoagulation within 1 month of the catheter ablation procedure.

11. Currently enrolled in another investigational device or drug trial that has not
completed the primary endpoint or that clinically interferes with the current study
endpoints.

12. Co-morbid condition(s) that could limit the subject's ability to participate in the
trial or to comply with follow-up requirements, or that could impact the scientific
integrity of the trial.

13. Platelet count ≤100,000/mm3.

14. Hemoglobin level <9 g/dL.

15. Any active bleeding.

16. Prisoners or subjects who are involuntarily incarcerated.

17. Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (e.g., infectious disease) illness.