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

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.

• Authors: Manesh R Patel, Anne S Hellkamp, Yuliya Lokhnygina, Jonathan P Piccini, Zhongxin Zhang, Surya Mohanty, Daniel E Singer, Werner Hacke, Günter Breithardt, Jonathan L Halperin, Graeme J Hankey, Richard C Becker, Christopher C Nessel, Scott D Berkowitz, Robert M Califf, Keith A A Fox, Kenneth W Mahaffey
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 61 Issue 6 Pg. 651-8 (Feb 12 2013) ISSN: 1558-3597 [Electronic] United States
• PMID: 23391196 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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