title: End of study transition from study drug to open-label vitamin K antagonist therapy: the ROCKET AF experience.
abstract: BACKGROUND
  To evaluate the previously reported excess of thromboembolic events during the 30 days after the end of study (EOS) visit when participants transitioned from blinded therapy to open-label vitamin K antagonist.
  
  
  RESULTS
  At the EOS visit, open-label vitamin K antagonist was recommended, and the international normalized ratio (INR) was not to be measured until 3 days later to preserve blinding. We analyzed transition strategies, clinical outcomes, and INR values. Event rates are per 100 patient-years. A total of 9248 (65%) participants were taking study drug at EOS, and, between days 3 and 30, an excess of stroke and systemic embolic events were observed in participants assigned to rivaroxaban (rivaroxaban 22 events, event rate 6.42; warfarin 6 events, event rate 1.73; hazard ratio, 3.72; 95% confidence interval, 1.51-9.16; P=0.0044). No INR values were reported for ≈5% of participants transitioned to warfarin. By 30 days after EOS, 83% of the warfarin group and 52% of the rivaroxaban group had ≥1 therapeutic INR value. Median time to first therapeutic INR was 3 days in the warfarin group and 13 days in the rivaroxaban group.
  
  
  CONCLUSIONS
  The excess of events at EOS was likely because of a period of inadequate anticoagulation in rivaroxaban participants switched to vitamin K antagonist therapy. If transition from rivaroxaban to vitamin K antagonist is needed, timely monitoring and careful dosing should be used to ensure consistent and adequate anticoagulation.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. kenneth.mahaffey@duke.edu
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.forename: Karen L
authors.initials: KL
authors.lastname: Hannan
authors.forename: Kimberly
authors.initials: K
authors.lastname: Schwabe
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.forename: Scott D
authors.initials: SD
authors.lastname: Berkowitz
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects*; D002985:Clinical Protocols; D003266:Continuity of Patient Care; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057915:Drug Substitution; D004617:Embolism / Q000209:etiology / Q000517:prevention & control*; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D012107:Research Design; D012307:Risk Factors; D000069552:Rivaroxaban; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors* / Q000097:blood; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014812:Vitamin K; D014859:Warfarin; D000069552:Rivaroxaban; D015951:Factor Xa
keywords: atrial fibrillation; bridging; discontinuations; factor Xa; randomized controlled trial; rivaroxaban; stroke