title: Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: analysis from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).
abstract: OBJECTIVE
  The purpose of this study was to understand the possible risk of discontinuation in the context of clinical care.
  
  
  BACKGROUND
  Rivaroxaban is noninferior to warfarin for preventing stroke in atrial fibrillation patients. Concerns exist regarding possible increased risk of stroke and non-central nervous system (CNS) thromboembolic events early after discontinuation of rivaroxaban.
  
  
  METHODS
  We undertook a post-hoc analysis of data from the ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation, n = 14,624) for stroke or non-CNS embolism within 30 days after temporary interruptions of 3 days or more, early permanent study drug discontinuation, and end-of-study transition to open-label therapy.
  
  
  RESULTS
  Stroke and non-CNS embolism occurred at similar rates after temporary interruptions (rivaroxaban: n = 9, warfarin: n = 8, 6.20 vs. 5.05/100 patient-years, hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 0.49 to 3.31, p = 0.62) and after early permanent discontinuation (rivaroxaban: n = 42, warfarin: n = 36, 25.60 vs. 23.28/100 patient-years, HR: 1.10, 95% CI: 0.71 to 1.72, p = 0.66). Patients transitioning to open-label therapy at the end of the study had more strokes with rivaroxaban (n = 22) versus warfarin (n = 6, 6.42 vs. 1.73/100 patient-years, HR: 3.72, 95% CI: 1.51 to 9.16, p = 0.0044) and took longer to reach a therapeutic international normalized ratio with rivaroxaban versus warfarin. All thrombotic events within 30 days of any study drug cessation (including stroke, non-CNS embolism, myocardial infarction, and vascular death) were similar between groups (HR: 1.02, 95% CI: 0.83 to 1.26, p = 0.85).
  
  
  CONCLUSIONS
  In atrial fibrillation patients who temporarily or permanently discontinued anticoagulation, the risk of stroke or non-CNS embolism was similar with rivaroxaban or warfarin. An increased risk of stroke and non-CNS embolism was observed in rivaroxaban-treated patients compared with warfarin-treated patients after the end of the study, underscoring the importance of therapeutic anticoagulation coverage during such a transition.
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA. manesh.patel@duke.edu
authors: Manesh R
authors: MR
authors: Patel
authors: Anne S
authors: AS
authors: Hellkamp
authors: Yuliya
authors: Y
authors: Lokhnygina
authors: Jonathan P
authors: JP
authors: Piccini
authors: Zhongxin
authors: Z
authors: Zhang
authors: Surya
authors: S
authors: Mohanty
authors: Daniel E
authors: DE
authors: Singer
authors: Werner
authors: W
authors: Hacke
authors: Günter
authors: G
authors: Breithardt
authors: Jonathan L
authors: JL
authors: Halperin
authors: Graeme J
authors: GJ
authors: Hankey
authors: Richard C
authors: RC
authors: Becker
authors: Christopher C
authors: CC
authors: Nessel
authors: Scott D
authors: SD
authors: Berkowitz
authors: Robert M
authors: RM
authors: Califf
authors: Keith A A
authors: KA
authors: Fox
authors: Kenneth W
authors: KW
authors: Mahaffey
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D001777:Blood Coagulation / Q000187:drug effects*; D016903:Drug Monitoring / Q000379:methods; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects; D017063:Outcome Assessment, Health Care; D018570:Risk Assessment / Q000379:methods* / Q000706:statistics & numerical data; D000069552:Rivaroxaban; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects; D013923:Thromboembolism / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects; D028761:Withholding Treatment / Q000706:statistics & numerical data
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014859:Warfarin; D000069552:Rivaroxaban