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).

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Patel, MR; Hellkamp, AS; Lokhnygina, Y; Piccini, JP; Zhang, Z; Mohanty, S; Singer, DE; Hacke, W; Breithardt, G; Halperin, JL; Hankey, GJ; Becker, RC; Nessel, CC; Berkowitz, SD; Califf, RM; Fox, KAA; Mahaffey, KW

Published Date

  • February 2013

Published In

Volume / Issue

  • 61 / 6

Start / End Page

  • 651 - 658

PubMed ID

  • 23391196

Pubmed Central ID

  • 23391196

Electronic International Standard Serial Number (EISSN)

  • 1558-3597

International Standard Serial Number (ISSN)

  • 0735-1097

Digital Object Identifier (DOI)

  • 10.1016/j.jacc.2012.09.057

Language

  • eng