Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF)

Abstract

Background: During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI.

Methods and results: In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32).

Conclusions: TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Keywords: anticoagulation; atrial fibrillation; stroke.

Figures

Figure 1

Cumulative incidence plot of time to first temporary interruption by treatment group, showing the longitudinal analysis for time to first temporary interruption for warfarin- and rivaroxaban-treated patients. Warfarin-treated patients were significantly more likely to experience temporary interruption during follow-up.

Figure 2

Distribution of surgical/invasive procedures requiring temporary interruption, showing the frequency of different types of surgical procedures that were listed as reasons for temporary interruptions in the Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Abd indicates abdominal; Bx, biopsy; CABG, coronary artery bypass graft; EP, electrophysiology; GI, gastrointestinal; Ortho, orthopedic; PCI, percutaneous coronary intervention; and Thora, thoracic. Abd = Abdominal, Thora = Thoracic, Ortho = Orthopedic, Bx = Biopsy, EP = Electrophysiology, PCI = Percutaneous coronary intervention, CABG = Coronary artery bypass graft