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)

J Am Coll Cardiol. 2013 Feb 12;61(6):651-8. doi: 10.1016/j.jacc.2012.09.057.

Abstract

Objectives: 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.

Publication types

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

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / mortality
  • Blood Coagulation / drug effects*
  • Drug Monitoring / methods
  • Factor Xa Inhibitors
  • Female
  • Humans
  • International Normalized Ratio
  • Male
  • Morpholines* / administration & dosage
  • Morpholines* / adverse effects
  • Outcome Assessment, Health Care
  • Risk Assessment / methods*
  • Risk Assessment / statistics & numerical data
  • Rivaroxaban
  • Stroke / blood
  • Stroke / etiology
  • Stroke / prevention & control*
  • Thiophenes* / administration & dosage
  • Thiophenes* / adverse effects
  • Thromboembolism / blood
  • Thromboembolism / etiology
  • Thromboembolism / prevention & control*
  • Time Factors
  • Warfarin* / administration & dosage
  • Warfarin* / adverse effects
  • Withholding Treatment / statistics & numerical data

Substances

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