Clinical outcomes with rivaroxaban in patients transitioned from vitamin K antagonist therapy: a subgroup analysis of a randomized trial

Ann Intern Med. 2013 Jun 18;158(12):861-8. doi: 10.7326/0003-4819-158-12-201306180-00003.


Background: In 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), a large randomized, clinical trial, rivaroxaban was noninferior to warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation.

Objective: To determine the efficacy and safety of rivaroxaban compared with warfarin among vitamin K antagonist (VKA)-naive and VKA-experienced patients.

Design: Prespecified subgroup analysis. ( NCT00403767).

Setting: Global.

Patients: 14,264 persons with atrial fibrillation.

Measurements: Interaction of the relative treatment effect of rivaroxaban and warfarin on stroke or systemic embolism among VKA-naive and VKA-experienced patients.

Results: Overall, 7897 (55.4%) patients were VKA-experienced and 6367 (44.6%) were VKA-naive. The effect of rivaroxaban versus warfarin on stroke or systemic embolism was consistent: Rates per 100 patient-years of follow-up were 2.32 versus 2.87 for VKA-naive patients (hazard ratio [HR], 0.81 [95% CI, 0.64 to 1.03]) and 1.98 versus 2.09 for VKA-experienced patients (HR, 0.94 [CI, 0.75 to 1.18]; interaction P = 0.36). During the first 7 days, rivaroxaban was associated with more bleeding than warfarin (HR in VKA-naive patients, 5.83 [CI, 3.25 to 10.44], and in VKA-experienced patients, 6.66 [CI, 3.83 to 11.58]; interaction P = 0.53). After 30 days, rivaroxaban was associated with less bleeding than warfarin in VKA-naive patients (HR, 0.84 [CI, 0.74 to 0.95]) and similar bleeding in VKA-experienced patients (HR, 1.06 [CI, 0.96 to 1.17]; interaction P = 0.003).

Limitation: The trial was not designed to detect differences in these subgroups.

Conclusion: The efficacy of rivaroxaban in VKA-experienced and VKA-naive patients was similar to that of the overall trial. There were more bleeding events within 7 days of study drug initiation with rivaroxaban, but after 30 days, rivaroxaban was associated with less bleeding in VKA-naive patients and similar bleeding in VKA-experienced patients. This information may be useful to clinicians considering a transition to rivaroxaban for patients receiving VKA therapy.

Primary funding source: Johnson & Johnson and Bayer HealthCare.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / complications*
  • Comparative Effectiveness Research
  • Embolism / prevention & control*
  • Factor Xa Inhibitors
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Morpholines / adverse effects
  • Morpholines / therapeutic use*
  • Rivaroxaban
  • Stroke / prevention & control*
  • Thiophenes / adverse effects
  • Thiophenes / therapeutic use*
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors*
  • Warfarin / adverse effects
  • Warfarin / therapeutic use*


  • Anticoagulants
  • Factor Xa Inhibitors
  • Morpholines
  • Thiophenes
  • Vitamin K
  • Warfarin
  • Rivaroxaban

Associated data