title: Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial.
abstract: BACKGROUND
  In the PROTECT AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) trial that evaluated patients with nonvalvular atrial fibrillation (NVAF), left atrial appendage (LAA) occlusion was noninferior to warfarin for stroke prevention, but a periprocedural safety hazard was identified.
  
  
  OBJECTIVE
  The goal of this study was to assess the safety and efficacy of LAA occlusion for stroke prevention in patients with NVAF compared with long-term warfarin therapy.
  
  
  METHODS
  This randomized trial further assessed the efficacy and safety of the Watchman device. Patients with NVAF who had a CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and previous stroke/transient ischemic attack) score ≥2 or 1 and another risk factor were eligible. Patients were randomly assigned (in a 2:1 ratio) to undergo LAA occlusion and subsequent discontinuation of warfarin (intervention group, n = 269) or receive chronic warfarin therapy (control group, n = 138). Two efficacy and 1 safety coprimary endpoints were assessed.
  
  
  RESULTS
  At 18 months, the rate of the first coprimary efficacy endpoint (composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death) was 0.064 in the device group versus 0.063 in the control group (rate ratio 1.07 [95% credible interval (CrI): 0.57 to 1.89]) and did not achieve the prespecified criteria noninferiority (upper boundary of 95% CrI ≥1.75). The rate for the second coprimary efficacy endpoint (stroke or SE >7 days' postrandomization) was 0.0253 versus 0.0200 (risk difference 0.0053 [95% CrI: -0.0190 to 0.0273]), achieving noninferiority. Early safety events occurred in 2.2% of the Watchman arm, significantly lower than in PROTECT AF, satisfying the pre-specified safety performance goal. Using a broader, more inclusive definition of adverse effects, these still were lower in PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial than in PROTECT AF (4.2% vs. 8.7%; p = 0.004). Pericardial effusions requiring surgical repair decreased from 1.6% to 0.4% (p = 0.027), and those requiring pericardiocentesis decreased from 2.9% to 1.5% (p = 0.36), although the number of events was small.
  
  
  CONCLUSIONS
  In this trial, LAA occlusion was noninferior to warfarin for ischemic stroke prevention or SE >7 days' post-procedure. Although noninferiority was not achieved for overall efficacy, event rates were low and numerically comparable in both arms. Procedural safety has significantly improved. This trial provides additional data that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF who do not have an absolute contraindication to short-term warfarin therapy.
authors.affiliation: Mayo Clinic, Rochester, Minnesota. Electronic address: holmes.david@mayo.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Holmes
authors.affiliation: Cedars Sinai Medical Center, Los Angeles, California.
authors.forename: Saibal
authors.initials: S
authors.lastname: Kar
authors.affiliation: Scripps Clinic, La Jolla, California.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Price
authors.affiliation: Intermountain Medical Center, Salt Lake City, Utah.
authors.forename: Brian
authors.initials: B
authors.lastname: Whisenant
authors.affiliation: Cardiovasculares Centrum, Frankfurt, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Sievert
authors.affiliation: Pacific Heart Institute, Santa Monica, California.
authors.forename: Shephal K
authors.initials: SK
authors.lastname: Doshi
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, Missouri.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Huber
authors.affiliation: Mount Sinai School of Medicine, New York, New York.
authors.forename: Vivek Y
authors.initials: VY
authors.lastname: Reddy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D020517:Atrial Appendage / Q000473:pathology / Q000601:surgery*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery*; D006348:Cardiac Surgical Procedures / Q000592:standards*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: atrial fibrillation; left atrial appendage; stroke prevention