EdoxabaN or Warfarin Therapy In Cardiovascular Implantable Electrical Device Procedures in Patients With Non-Valvular Atrial Fibrillation

This is a prospective randomized comparative evaluation of Edoxaban and Warfarin for safety
and efficacy in perioperative use in patients with non-valvular atrial fibrillation
undergoing clinically indicated implantation or replacement of cardiovascular implantable
electrical devices. This study is a randomized, open label, active-controlled trial with an
open-label safety extension, designed to compare local and systemic bleeding within 30 days
of cardiac rhythm device implant among subjects randomized to continuous Warfarin or
interrupted (<24 hours) Edoxaban. The study will have three phases, a run in phase to
establish stable warfarin therapy, an acute open label 30 day phase when subjects will be
randomized in a 1:1 ratio to receive interrupted edoxaban or continuous warfarin followed by
an open label follow up phase for an additional 5 months for safety monitoring. Drug
transitions will be performed according to approved drug labeling.

Inclusion Criteria:

- Subjects with established atrial fibrillation (AF) and bradycardia on long term (>3
weeks) therapeutic oral anticoagulant (OAC) with warfarin or another OAC who are
undergoing new pacemaker system implant or existing pacemaker system revision.

- Subjects with newly detected bradycardia -tachycardia syndrome and AF who have been
recently (less than 3 weeks) started on warfarin, have a therapeutic international
normalized ratio (INR) and no thrombus on trans-esophageal echocardiogram (TEE) who
are undergoing a new pacemaker system implant or revision.

- Subjects with AF and ventricular tachyarrhythmias (VT or VF) or acquired structural
heart disease who are candidates for implantable cardioverter-defibrillator (ICD)
therapy and are on long term (>3 weeks) therapeutic OAC with warfarin or another OAC
who are undergoing new ICD system implant or existing ICD system revision.

- Subjects with newly detected AF with VT or VF who have been recently (less than 3
weeks) started on warfarin, have a therapeutic INR and no thrombus on TEE who are
undergoing ICD system implant or revision

Exclusion Criteria:

- Clinically significant valvular heart disease

- Subjects requiring cardiovascular implantable electrical device (CIED) lead
extraction e.g. for device site infection, endocarditis, leads under advisory or
other conditions warranting lead(s) system extraction.

- Recent (<1 month) myocardial infarction

- Documented left atrial (LA) thrombus on TEE

- Contraindications to anticoagulant therapy or adverse event with prior warfarin or
edoxaban therapy

- Creatinine clearance <30ml/min or >95 ml/min

- Hepatic disease, advanced

- Recent stroke (<3 months) or thromboembolic event

- Recent (<3months) intracranial or other major bleeding event

- Use of concomitant dual antiplatelet therapy or other oral, subcutaneous or
parenteral anticoagulant therapy

- Subjects on warfarin without therapeutic INR levels before study entry

- Subjects with other clinically significant medical condition

- Subjects with life expectancy < 1 year

- Lead extraction procedures