Safety and Efficacy of Rivaroxaban in Patients With Cardiac Implantable Electronic Devices: Observations From the ROCKET AF Trial

George C Leef, Anne S Hellkamp, Manesh R Patel, Richard C Becker, Scott D Berkowitz, Günter Breithardt, Jonathan L Halperin, Graeme J Hankey, Werner Hacke, Christopher C Nessel, Daniel E Singer, Keith A A Fox, Kenneth W Mahaffey, Jonathan P Piccini, George C Leef, Anne S Hellkamp, Manesh R Patel, Richard C Becker, Scott D Berkowitz, Günter Breithardt, Jonathan L Halperin, Graeme J Hankey, Werner Hacke, Christopher C Nessel, Daniel E Singer, Keith A A Fox, Kenneth W Mahaffey, Jonathan P Piccini

Abstract

Background: Although implantation of cardiac implantable electronic devices (CIEDs) in patients receiving warfarin is well studied, limited data are available on the use of oral factor Xa inhibitors in this setting.

Methods and results: Using data from 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) (n=14 264), we compared baseline characteristics and clinical outcomes in patients with atrial fibrillation randomized to rivaroxaban versus warfarin who did and did not undergo CIED implantation or revision. In this post-hoc, postrandomization, on-treatment analysis, only the first intervention per patient was analyzed. During a median follow-up of 2.2 years, 453 patients (242 rivaroxaban group; 211 warfarin group) underwent de novo CIED implantation (64.2%) or revision procedures (35.8%). Patients who received CIEDs were older, more likely to be male, and more likely to have past myocardial infarction, but had similar stroke risk compared to patients who did not receive CIEDs. Most patients who received a device had study drug interrupted for the procedure and did not receive bridging anticoagulation. During the 30-day postprocedural period, 11 patients (4.55%) in the rivaroxaban group experienced bleeding complications compared with 15 (7.13%) in the warfarin group. Thromboembolic complications occurred in 3 patients (1.26%) in the rivaroxaban group and 1 (0.48%) in the warfarin group. Event rates were too low for formal hypothesis testing.

Conclusions: Bleeding and thromboembolic events were low in both rivaroxaban- and warfarin-treated patients. Periprocedural use of oral factor Xa inhibitors in CIED implantation requires further study in prospective, randomized trials.

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

Keywords: anticoagulation; atrial fibrillation; cardiac resynchronization therapy; factor Xa inhibitor; implantable cardioverter‐defibrillator; pacemaker; rivaroxaban; warfarin.

© 2017 The Authors, Bayer US LLC, and Janssen Research and Development. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
Flow chart depicting all patients who underwent CIED procedures and exclusions from this analysis. *Patients not receiving study drug—at any time or after permanent discontinuation—were followed for efficacy events only. Other events were occasionally, but not systematically, recorded. Thus, 28 patients who never received study drug are omitted from the analysis, because both postimplant device status and safety (bleeding) events are unknown, and 4 patients who underwent a device‐related procedure (replacement) after the end of study drug are omitted because (1) it is unlikely they are a complete accounting of device‐related procedures during that period and (2) their safety event status is unknown. †Violations in good clinical practice guidelines at 1 site made their efficacy data unreliable; patients from this site are omitted from all efficacy analyses. Safety data were unaffected. ‡Patients were included in the 30 and 90 days pre‐ and postprocedure TTR summaries only if they had actual or imputed INR values for at least two thirds of the days in question. For the preprocedure groups, patients were omitted if their procedure occurred too soon after randomization to provide a sufficient number of days of INR values. For postprocedure groups, patients were omitted if they stopped the study drug before the end of the period in question. CIED indicates cardiac implantable electronic devices; GCP, Good Clinical Practice; INR, international normalized ratio; TTR, time in therapeutic range.
Figure 2
Figure 2
Study drug interruption and bridging therapy at the time of CIED‐related procedure. CIED indicates cardiac implantable electronic devices; LMWH, low‐molecular‐weight heparin; R, rivaroxaban; W, warfarin.

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