Bayer HealthCare has announced results from the X- VeRT* study, demonstrating that once-daily Xarelto® (rivaroxaban) is an effective and well-tolerated alternative to dose-adjusted vitamin K antagonists (VKAs) such as warfarin, in patients with non- valvular AF undergoing cardioversion, which may also allow for more timely cardioversion.1

X-VeRT, the first completed prospective trial of any novel oral anticoagulant (NOAC) in patients undergoing elective cardioversion, showed that rivaroxaban was as effective and with a similar safety profile as well-controlled warfarin. In this exploratory study, rivaroxaban demonstrated effective protection with an event rate comparable to VKA in the primary efficacy endpoint - composite of all stroke, transient ischaemic attack, peripheral embolism, myocardial infarction and cardiovascular death (0.51 vs. 1.02%, RR 0.5, CI 0.15-1.73).1 In the primary safety endpoint of major bleeding, rivaroxaban demonstrated a comparable safety profile with no increase vs. VKA (0.61% vs. 0.8 %, RR 0.76, CI 0.21-2.67) in the incidence of major and non-major bleeding events (relative risk reduction of 24%, ARR 0.19).11 The practical advantage of using rivaroxaban was demonstrated by the shorter time frame to cardioversion compared with treatment using warfarin in the delayed cardioversion group (median of 22 days vs. 30 days respectively, p<0.001).11

The study was designed primarily to further explore prospectively the efficacy and safety of once- daily rivaroxaban compared with dose-adjusted VKA treatment, as well as to support previous findings of rivaroxaban in the setting of cardioversion from ROCKET AF and was not powered for statistical significance. These data were presented today during the Hot Line Session at the ESC Congress 2014 and published simultaneously in the European Heart Journal.

"Until now, there has been a lack of dedicated prospective clinical trial data to guide physicians on the practical use of NOACs in AF patients scheduled to undergo cardioversion," said Professor Diana Gorog, Consultant Cardiologist at East & North Hertfordshire NHS Trust, who was the UK Chief Investigator for the X-VeRT trial.

INR levels can fluctuate in patients with warfarin, which can lead to delay in elective cardioversion; a problem that is eliminated by the fixed-dose anticoagulation provided by NOACs." Cardioversion is a common medical procedure undertaken in patients with AF in order to reset the heartbeat back to a regular sinus rhythm. Without adequate anticoagulation patients have a risk of thromboembolic complications, with stroke rates of 5-7%.1 Current guidelines recommend effective anticoagulation with VKAs takes place for at least three weeks (target INR 2.0-3.0) prior to cardioversion (or less if a transesophageal echocardiogram has revealed no thrombus in the left atrium or left atrial appendage) and four weeks of oral anticoagulation is continued after the procedure has taken place.2,3

However, unstable INR levels with VKA anticoagulation often result in the cancellation or postponement of cardioversion, underlining the need for stable, effective anticoagulation in these patients to help prevent life-threatening blood clots before, during and after the procedure.

"Treating an AF patient undergoing elective cardioversion with a Xaban, such as Xarelto, to me is a good solution," said Dr Oliver Segal, Consultant Cardiac Electrophysiologist, The Heart Hospital. "When undergoing VKA treatment, a patient‟s INR can be inconsistent and out of range causing delays to cardioversion. Whilst high INRs place patients at an increased risk of bleeding, Xarelto offers a fixed dose regime, a reliable level of anticoagulation and reduced medical contact until cardioversion is due to take place. It‟s once-daily dosing may also aid patient adherence."

The X-VeRT study contributes to the extensive on-going evaluation of rivaroxaban that will include more than 275,000 patients in both clinical trials and real world settings. "These important insights contribute to the expansion of our understanding of the clinical utility of Xarelto across different settings and patient populations," said Dr Luis Felipe Graterol, Medical Director, Bayer HealthCare UK. "Once-daily Xarelto is the leader in the Xaban/DTI market place both in the UK and worldwide and is the preferred anticoagulant by some margin. X-VeRT is a key part of Bayer‟s commitment to responsible and wider use of Xarelto where effective and reliable anticoagulation is needed. It is an important study in our growing clinical trial and lifecycle management programme."

About the X-VeRT Study

X-VeRT was a prospective, randomised, open-label, parallel group Phase IIIb study involving 1,504 patients with hemodynamically stable non-valvular AF of > 48 hours or unknown duration, recruited from 16 countries worldwide. Anticoagulation naïve or experienced patients scheduled for cardioversion were randomly assigned to rivaroxaban 20mg once-daily (15mg once-daily if creatinine clearance was between 30-49 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. AF patients on rivaroxaban demonstrated a numerically reduced risk of cardiovascular events of 50% (ARR 0.51) compared to VKA, as well as a reassuring bleeding profile with a numerically lower major bleeding incidence risk of 24% (ARR 0.19).

Overall, the mean time from randomisation to cardioversion was similar in patients assigned to rivaroxaban compared to those assigned to VKA treatment in the early cardioversion group early: 1.8±1.6 days vs 2.1±3.0 days, P = 0.628); but was shorter with rivaroxaban in the delayed cardioversion group (24.6±5.6 days vs 33.7±13.1 days, P < 0.001). The positive rivaroxaban efficacy and safety outcomes findings were consistent in both early and delayed cardioversion strategies. These results were not statistically significant as the trial was not powered accordingly.

About Xarelto® (Rivaroxaban)

Rivaroxaban is the most broadly indicated NOAC and is marketed under the brand name Xarelto. To date, Xarelto has been approved for use in more than 125 countries, across all indications, and in the UK specifically to date across the following indications: 4

  • The prevention of stroke and systemic embolism in adult patients with non-valvular AF with one or more risk factors.
  • The treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of recurrent DVT and PE in adults.
  • The prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery.
  • The prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers, co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine.*

* NB. Please note that Xarelto is not commercially available in the UK for this indication

Since the first approval of Xarelto in the orthopaedic setting in 2008, 9.2 million patients worldwide have received Xarelto in daily clinical practice.5

Rivaroxaban was discovered by Bayer HealthCare, and is being jointly developed with Janssen Research & Development, LLC. Xarelto is marketed outside the U.S. by Bayer HealthCare and in the U.S. by Janssen Pharmaceuticals, Inc. (a Johnson & Johnson Company).

Anticoagulant medicines are potent therapies used to prevent and treat blood clots whose consequences may be serious, or to treat serious illnesses and potentially life-threatening conditions. Before initiating therapy with anticoagulant medicines, physicians should carefully assess the benefit and risk for the individual patient.

Responsible use of Xarelto is a very high priority for Bayer, and the company has developed a "Prescriber‟s Guide‟ for physicians and a "Xarelto Patient Card‟ for patients to support best practice.