This prospective, randomized, multicenter study will enroll 3,181 subjects (2706 randomized subjects, 225 roll-in subjects, and 250 subjects in a registry) at up to 75 investigational sites in the United States. Patients presenting with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism based on CHA2DS2-VASc scores, and who are recommended for oral anticoagulation therapy but have an appropriate rationale to seek a non-pharmacologic alternative to oral anticoagulation, and who meet all eligibility criteria will be enrolled in the study.~Subjects will have clinical follow-up in-hospital and at 45 days, 6 months, 12 months, and annually up to 5-years. CT/Imaging or Transesophageal echocardiographic (TEE) follow-up will occur at 45 days and TEE at 1-year.~The LAmbre PlusTM Left Atrial Appendage (LAA) Closure System is intended to reduce the risk of thromboembolism from the left atrial appendage (LAA) in patients with nonvalvular atrial fibrillation who:~Are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc scores and are recommended for oral anticoagulation (OAC) therapy; AND~Are deemed by their physician to be suitable for OAC; AND~Have an appropriate rationale to seek a non-pharmacological alternative to OAC, taking into account the safety and effectiveness of the device compared to OAC
The primary objective is to demonstrate the safety and efficacy of the implantation of the LAmbre PlusTM device in patients with large or irregularly shaped appendages with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism compared to oral anticoagulation (OAC).