title: Left Atrial Appendage Occlusion Device and Novel Oral Anticoagulants Versus Warfarin for Stroke Prevention in Nonvalvular Atrial Fibrillation: Systematic Review and Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Nonvalvular atrial fibrillation is the most common arrhythmia. Patients with nonvalvular atrial fibrillation are at increased risk of stroke; therefore, we evaluated the efficacy and safety of different approaches to prevent this major complication.
  
  
  RESULTS
  We conducted electronic database searches of phase III randomized controlled trials. The groups were novel oral anticoagulants, Watchman left atrial appendage occlusion device (DEVICE), and warfarin. Efficacy outcomes were stroke or systemic embolism, and all-cause mortality. Safety outcome was major bleeding and procedure-related complications. A subgroup analysis of the elderly population was done. We used random-effects model to compare pooled outcomes and tested for heterogeneity. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for each outcome. Seven randomized controlled trials (n=73,978) were included. There was a significant difference favoring novel oral anticoagulants for systemic embolism (OR, 0.84; 95% CI, 0.72-0.97; P=0.01), all-cause mortality (OR, 0.89; 95% CI, 0.84-0.94; P<0.001), and safety outcomes (OR, 0.79; 95% CI, 0.65-0.97; P=0.026) compared with warfarin. No difference was seen between DEVICE and warfarin for efficacy end points; however, DEVICE had more complications (OR, 1.85; 95% CI, 1.14-3.01; P=0.012). In the elderly (6 randomized controlled trials, n=30,699), systemic embolism was favored with novel oral anticoagulants over warfarin (OR, 0.77; 95% CI, 0.68-0.87; P≤0.001). No evidence of significant publication bias was found.
  
  
  CONCLUSIONS
  Novel oral anticoagulants is superior to warfarin for stroke prevention in nonvalvular atrial fibrillation. This benefit was also observed in the elderly population. DEVICE is a reasonable noninferior alternative to warfarin for stroke prevention, but cautious use is essential given safety concerns.
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: David F
authors.initials: DF
authors.lastname: Briceno
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Pedro
authors.initials: P
authors.lastname: Villablanca
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Nicole
authors.initials: N
authors.lastname: Cyrille
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Daniele
authors.initials: D
authors.lastname: Massera
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Eric
authors.initials: E
authors.lastname: Bader
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Eric
authors.initials: E
authors.lastname: Manheimer
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Philip
authors.initials: P
authors.lastname: Aagaard
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Kevin
authors.initials: K
authors.lastname: Ferrick
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Jay
authors.initials: J
authors.lastname: Gross
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Soo Gyum
authors.initials: SG
authors.lastname: Kim
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Krumerman
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Eugen
authors.initials: E
authors.lastname: Palma
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Nils
authors.initials: N
authors.lastname: Guttenplan
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Jorge
authors.initials: J
authors.lastname: Romero
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: John
authors.initials: J
authors.lastname: Fisher
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Mario
authors.initials: M
authors.lastname: Garcia
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).
authors.forename: Andrea
authors.initials: A
authors.lastname: Natale
authors.affiliation: From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.). dibbia@gmail.com.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Biase
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage*; D020517:Atrial Appendage / Q000601:surgery*; D001281:Atrial Fibrillation / Q000150:complications / Q000628:therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D055989:Septal Occluder Device; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: anticoagulants; atrial appendage; atrial fibrillation; stroke; warfarin