WAVECREST2WAveCrest Vs. Watchman TranssEptal LAA Closure to REduce AF-Mediated STroke 2. A Prospective, Multicenter, Randomized, Active Controlled, Clinical Trial of the Coherex WaveCrest® Left Atrial Appendage Occlusion System Compared to the Watchman® LAA Closure Device for the Reduction in Risk of Ischemic Stroke or Systemic Embolism in Subjects With Non-valvular Atrial Fibrillation That Have an Appropriate Rationale to Seek a Non-pharmacologic Alternative to Chronic Oral Anticoagulation.

Study start date: December 27, 2017

Inclusion Criteria: 1. Documented evidence of paroxysmal, persistent, or permanent non-valvular atrial fibrillation 2. At least 18 years of age 3. Calculated CHADS2 score ≥ 2 or CHA2DS2-VASc score ≥ 3 4. Indication for warfarin therapy with an appropriate rationale to seek a non-pharmacologic alternative to chronic oral anticoagulation 5. Willing and able to comply with post-implant anticoagulation and antiplatelet regimen 6. Willing to participate in the required follow-up visits and tests 7. Subject has been informed of the nature of the trial, agrees to its provisions and has provided written informed consent as approved by the IRB/EC at the site Exclusion Criteria: 1. Atrial fibrillation (AF) due to a reversible cause (e.g. thyrotoxicosis or postoperative) 2. Known contraindication and/or allergy to warfarin, nickel, aspirin, intravenous contrast or P2Y12 inhibitors (clopidogrel, ticagrelor, and prasugrel), which cannot be adequately pre-medicated or desensitized 3. Conditions other than AF requiring long-term anticoagulation therapy 4. Contraindications for percutaneous catheterization procedures 5. Prior surgical LAA occlusion/exclusion or implanted with LAA occlusion device, or any prior attempt of such procedures 6. Prior percutaneous or surgical closure of a patent foramen ovale or atrial septal defect 7. Inability or unwillingness to take oral anticoagulation for 45 days post-procedure 8. New York Heart Association (NYHA) Class IV heart failure 9. Prior cardiac transplant, history of mitral valve replacement or transcatheter mitral valve intervention, or any mechanical valve implant 10. History of symptomatic carotid, intervertebral, or intracranial artery occlusion or stenosis without revascularization with the exception of known occlusion without symptoms \> 6 months 11. Modified Rankin Scale (mRS) score ≥ 4 12. Chronic resting heart rate ≥ 110 bpm 13. Congenital cardiac anomalies requiring cardiac surgery or interventional repair 14. Stroke or transient ischemic attack (confirmed by Neurologist) within 60 days prior to enrollment 15. Myocardial infarction within 60 days prior to enrollment 16. Sepsis or any infection requiring oral antibiotic therapy within 14 days or intravenous antibiotic therapy within 30 days prior to enrollment 17. Surgical or interventional cardiovascular and non-cardiovascular procedure including cardioversion within 30 days prior to enrollment or AF ablation within 60 days prior to enrollment or any planned general surgery or interventional procedure within 90 days after enrollment or any planned cardiac surgery. 18. On renal replacement therapy, serum creatinine \> 3.0 mg/dl (265 μmol/L) or calculated creatinine clearance \< 25 ml/minute 19. Thrombocytopenia (\<60,000 platelets/mm3), leucopenia (white blood cell count \< 3,000 cells/mm³), or anemia (hemoglobin concentration \< 10 grams/deciliter) based on blood work done within 30 days prior to enrollment 20. Any medical disorder or psychiatric illness that would interfere with successful completion of the trial 21. Currently participating in an investigational drug trial or another device trial that has not completed the primary endpoint (trials requiring extended follow-up for products that are commercially available are not considered investigational trials). Concurrent enrollment in the ACC LAAO Registry is permitted. 22. Subject belongs to a vulnerable population (see definition in Appendix I: Acronyms and Definitions) 23. Any condition that would reduce life expectancy to less than 2 years 24. Women of childbearing potential who are, or plan to become pregnant during the time of the trial (method of assessment per physician discretion) Echocardiographic Exclusion Criteria 1. Left ventricular ejection fraction \< 30% 2. Mitral valve stenosis defined as valve area \< 1.5cm2, mean gradient \> 6mmHg, or any valve deformity consistent with rheumatic valvular disease 3. Aortic valve stenosis defined as valve area ≤1.0cm2 or mean gradient \>30mmHg 4. Circumferential pericardial effusion \> 10mm or symptomatic pericardial effusion 5. Evidence of intracardiac thrombus 6. Cardiac tumor or myxoma 7. Atrial septal defect that warrants closure 8. Complex atheroma in the ascending aorta or aortic arch as evidenced by mobile plaque 9. Left Atrial Appendage size and shape are unsuitable for closure with a WaveCrest or Watchman device