This label update provides physicians with important information on the clinical utility of rivaroxaban in patients with AF who require cardioversion and is based on the positive CHMP opinion issued in December 2014. It makes Xarelto the only novel oral anticoagulant with specific label guidance for both early and delayed cardioversion.
"Providing adequate anticoagulation therapy for patients with AF undergoing cardio-version is important. With warfarin, patients will often move in and out of the therapeutic range for optimal anticoagulation often requiring postponement of their procedure or leading to increased risk of thromboembolic events like stroke," said Dr Riccardo Cappato, M.D., Arrhythmia and Electrophysiology Center, University of Milan, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy and Co-Principal Investigator of the X-VeRT study.
"The Xarelto label update provides physicians with clear guidance for patients with atrial fibrillation undergoing cardioversion. The X-VeRT study showed Xarelto to be an effective and well-tolerated alternative to vitamin K antagonists with a practical advantage over VKAs."
The label update is based on findings from the X-VeRT study, the first prospective trial of a novel oral anticoagulant in 1,504 patients with AF undergoing cardioversion.
The results from X-VeRT showed that compared with the use of VKA, rivaroxaban was associated with a numerical reduction in the risk of cardiovascular events of 50 per cent in the composite primary efficacy outcome of stroke, transient ischaemic attack, peripheral embolism, myocardial infarction and cardiovascular death (0.5% vs. 1.0%; risk reduction: 0.50; 95% confidence interval: 0.15-1.73), with a numerically lower risk of major bleeding of 24 per cent in the primary safety outcome (0.6% vs. 0.8%; risk reduction 0.76; 95% confidence interval: 0.21-2.67).
The practical advantage of using rivaroxaban was demonstrated by the shorter time to cardioversion compared to VKA, particularly in patients scheduled for delayed cardioversion. The study, published in the European Heart Journal in September 2014, was designed to supplement previous findings of rivaroxaban from ROCKET AF and was not powered for statistical significance.
Patients with AF experience an irregular heartbeat which causes turbulent blood flow that can lead to the formation of blood clots. Cardioversion is a common medical procedure undertaken to restore the heartbeat from AF back to its regular sinus rhythm. Without adequate anticoagulation, these patients are at risk of thromboembolic complications, with stroke rates of 5-7 per cent.
Current guidelines recommend at least three weeks of effective anticoagulation with VKAs (target INR 2.0-3.0) prior to cardioversion (or less if a transesophageal echocardiogram has revealed no thrombus in the left atrial or left atrial appendage) and four weeks of oral anticoagulation after the procedure.
X-VeRT was a prospective, randomised, open-label, parallel group Phase IIIb study involving 1,504 patients with hemodynamically stable non-valvular atrial fibrillation of > 48 hours or unknown duration, recruited from 16 countries.
Anticoagulation naïve or experienced patients scheduled for cardioversion were randomly assigned to rivaroxaban 20mg once daily (15mg once daily if creatinine clearance was between 30 and 49 mL/min) or INR-adjusted VKA therapy (target INR 2.0-3.0) in a 2:1 ratio.
The decision regarding early cardioversion (a goal of between 1-5 days of rivaroxaban or usual VKA therapy before the procedure) or delayed cardioversion (rivaroxaban or VKA for 3-8 weeks prior to the procedure) was taken by the local investigator.
The X-VeRT study contributes to the extensive investigation program of rivaroxaban. After its completion, the program will include more than 275,000 patients in clinical trials and real world settings.