title: Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial.
abstract: OBJECTIVE
  Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation.
  
  
  RESULTS
  Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6).
  
  
  CONCLUSIONS
  In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF.
authors.affiliation: Duke Clinical Research Institute, PO Box 17969, NC 27715 Durham, NC, USA benjamin.steinberg@duke.edu.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Steinberg
authors.affiliation: Duke Clinical Research Institute, PO Box 17969, NC 27715 Durham, NC, USA.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.affiliation: Duke Clinical Research Institute, PO Box 17969, NC 27715 Durham, NC, USA.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: Duke Clinical Research Institute, PO Box 17969, NC 27715 Durham, NC, USA.
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: Department of Cardiovascular Medicine, Hospital of the University of Münster, Münster, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.affiliation: Mount Sinai Medical Center, Cardiovascular Institute, New York, NY, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.affiliation: Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.affiliation: Janssen Research & Development LLC, Raritan, NJ, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.affiliation: Bayer HealthCare Pharmaceuticals, Montville, NJ, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Berkowitz
authors.affiliation: Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.affiliation: Duke University Medical Center, Duke Translational Medicine Institute, Durham, NC, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.affiliation: Duke Clinical Research Institute, PO Box 17969, NC 27715 Durham, NC, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000150:complications* / Q000401:mortality; D002423:Cause of Death; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009025:Morpholines / Q000008:administration & dosage; D011446:Prospective Studies; D012307:Risk Factors; D000069552:Rivaroxaban; D020521:Stroke / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control; D013876:Thiophenes / Q000008:administration & dosage; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014812:Vitamin K; D014859:Warfarin; D000069552:Rivaroxaban
keywords: Anticoagulation; Atrial fibrillation; Outcomes; Paroxysmal; Persistent