Rationale and design of the eXplore the efficacy and safety of once-daily oral riVaroxaban for the prEvention of caRdiovascular events in patients with nonvalvular aTrial fibrillation scheduled for cardioversion trial: A comparison of oral rivaroxaban once daily with dose-adjusted vitamin K antagonists in patients with nonvalvular atrial fibrillation undergoing elective cardioversion.
BACKGROUND
Anticoagulation before, during, and after cardioversion is effective in reducing stroke risk in patients with atrial fibrillation.


OBJECTIVE
The objective of this study is to explore the efficacy and safety of rivaroxaban 20 mg once daily (15 mg if creatinine clearance is 30-49 mL/min) compared with dose-adjusted vitamin K antagonists (VKAs; international normalized ratio 2.0-3.0) in patients scheduled for elective cardioversion.


METHODS
This is a prospective, randomized, open-label, parallel group comparison of approximately 1,500 patients from 17 countries with hemodynamically stable nonvalvular atrial fibrillation of >48 hours or unknown duration. Patients will be randomized 2:1 (rivaroxaban:VKA) using 2 cardioversion strategies: the first approach is early cardioversion with the precardioversion anticoagulation goal of 1 to 5 days using rivaroxaban or usual therapy (heparin + VKA). In these patients, transesophageal echocardiography will be encouraged to exclude atrial thrombi. The alternative approach is delayed cardioversion. Rivaroxaban or VKA will be administered for 21 to 56 days before cardioversion. All patients will receive study treatment for 6 weeks postcardioversion. The primary efficacy end point is a composite of all strokes, transient ischemic attacks, noncentral nervous system systemic emboli, myocardial infarctions, and cardiovascular deaths. Each primary end point component will be evaluated separately, and additional composites will be investigated. The principal safety end point is major bleeding.


METHODS
This will be the first prospective study of a novel oral anticoagulant in the setting of cardioversion. It will provide important information regarding the use of rivaroxaban in the periods preceding and after cardioversion in a broad patient population.
Cardiovascular Research Foundation, New York, NY; Jefferson Medical College, Philadelphia, PA.
Michael D
MD
Ezekowitz
Arrhythmia and Electrophysiology Center, University of Milan, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy; Department of Cardiology, Heraklion University Hospital, Heraklion (Crete), Greece.
Riccardo
R
Cappato
Department of Cardiovascular Medicine, Cleveland Clinic Heart and Vascular Institute, Cleveland, OH.
Allan L
AL
Klein
Division of Clinical Sciences, St George's, University of London, London, United Kingdom.
A John
AJ
Camm
Cardiology Division, Beijing AnZhen Hospital, Capital Medical University, Beijing, China.
Chang-Sheng
CS
Ma
Division of Cardiology and Arrhythmology, Hôpital Européen Georges Pompidou, Université Paris V René-Descartes, Paris, France.
Jean-Yves
JY
Le Heuzey
Department of Medicine, Research Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
Mario
M
Talajic
Arrhythmia Clinical Unit of Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
Maurício I
MI
Scanavacca
Department of Cardiology, Heraklion University Hospital, Heraklion (Crete), Greece.
Panos E
PE
Vardas
University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom; Department of Cardiology and Angiology, University Hospital Münster, Münster, Germany.
Paulus
P
Kirchhof
Department of Cardiology, Division of Clinical Electrophysiology, J.W. Goethe University, Frankfurt, Germany.
Stefan H
SH
Hohnloser
Global Clinical Development, Bayer Vital GmbH, Leverkusen, Germany.
Melanie
M
Hemmrich
Global Research and Development Statistics, Bayer HealthCare, Berlin, Germany.
Vivian
V
Lanius
Global Medical Affairs, Bayer HealthCare, Berlin, Germany.
Isabelle Ling
IL
Meng
Janssen Scientific Affairs, LLC, Raritan, NJ.
Peter
P
Wildgoose
Global Medical Affairs, Bayer HealthCare, Berlin, Germany.
Martin
M
van Eickels
D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017548:Echocardiography, Transesophageal; D004554:Electric Countershock; D004617:Embolism / Q000209:etiology / Q000517:prevention & control*; D065427:Factor Xa Inhibitors; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009025:Morpholines / Q000008:administration & dosage*; D011446:Prospective Studies; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014812:Vitamin K; D000069552:Rivaroxaban