X-VERT: Rivaroxaban (Xarelto) a Warfarin Alternative in AF Cardioversion, Without the INR

September 02, 2014

BARCELONA, SPAIN ( updated ) — In what may be the first prospective comparison of a new oral anticoagulant (NOAC) with warfarin or other vitamin-K antagonists (VKAs) in the setting of elective cardioversion for atrial fibrillation (AF), rivaroxaban (Xarelto, Bayer Pharma/Janssen Pharmaceuticals) was as effective and safe as a VKA when given for only about a week prior to the procedure[1]. Rivaroxaban appears likely to be a practical alternative to VKA in AF cardioversion as it can be given once daily, doesn't require INR checks, and seems not to need a protracted three-week treatment period before the procedure, as is typically done for warfarin, the study suggests.

The open-label but randomized trial, 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 (X-VERT), is reported today in the European Heart Journal, with lead author Dr Riccardo Cappato (University of Milan, Italy). Cappato is also scheduled to present the study here today at the European Society of Cardiology (ESC) 2014 Congress .

Dr Riccardo Cappato

The authors caution in the report that the trial was "underpowered to provide statistically rigorous results and was thus exploratory in nature." To heartwire ,Cappato said an adequately powered trial would have been prohibitively difficult and expensive, requiring >10 times as many patients. But X-VERT still adds to current understanding of NOACs with cardioversion, he said, and provides a high level of "solid, methodologically sound evidence" for those in clinical practice who are already using them in that setting instead of VKA.

In a 2:1 ratio, the group randomized 1504 patients with hemodynamically stable nonvalvular AF of either 48-hour or unknown duration to anticoagulation before and after cardioversion with once-daily rivaroxaban (20 mg/day; or 15 mg/day in patients with creatinine clearance 30–49 mL/min) or to standard titrated VKA.

Local investigators had the option of randomizing their patients to either an early- or delayed-cardioversion strategy. For early cardioversion, rivaroxaban or a VKA was given with a duration goal of one to five days prior to cardioversion and continued for six weeks after the procedure, the group reported.

The delayed-cardioversion strategy called for patients to receive rivaroxaban or a VKA for three to eight weeks before cardioversion; VKA treatment was considered adequate if the INR could be held at 2–3 for at least three weeks in a row before the procedure. Treatment with either agent was continued for six weeks after the procedure.

Of the entire cohort, 77.6% underwent cardioversion after anticoagulation within the target time ranges. Among patients who had been assigned to delayed cardioversion, 77% of those in the rivaroxaban group and only 36.3% of those who received VKA were cardioverted within the target time range (p<0.001). The primary reason for VKA-treated patients to get the procedure outside the target time ranges was failure to achieve adequate anticoagulation, the group writes.

Overall, rivaroxaban and VKA were comparably effective and safe.

Relative risk (95% CI) for Outcomes, Rivaroxaban vs Vitamin-K Antagonist Oral Anticoagulation in the Setting of AF Cardioversion

End points Rivaroxaban, n=978 (%) Vitamin-K Antagonist, n=492 (%) RR (95% CI) Rivaroxaban vs VKA
Primary efficacy outcomea 0.51 1.02 0.50 (0.15–1.73)
Primary safety outcomeb 0.61 0.80 0.76 (0.21–2.67)
Net clinical benefit outcomec 1.06 1.81 0.49 (0.14–1.69)
a. Stroke, transient ischemic attack, peripheral embolism, MI, or cardiovascular death
b. Major bleeding
c. Stroke, non–central-nervous-system systemic embolism, transient ischemic attack, MI, cardiovascular death, or major bleeding

Prof Jur Ten Berg (St Antonius Hospital, Nieuwegein, the Netherlands), who wasn't involved in X-VERT, told heartwire the trial "proves that if you choose to cardiovert these patients earlier, the NOAC is safe." He said that X-VERT, though of low statistical power, should be interpreted in conjunction with the large NOAC trials in nonvalvular AF, which taught a lot about the drugs' safety.

Ten Berg noted that the guidelines say to anticoagulate with VKA for three weeks before cardioversion, but the procedure must often be delayed because of difficulty in titrating to an appropriate INR—as X-VERT demonstrated. Sometimes heparin or a low-molecular weight heparin must be added, or transesophageal echocardiography—which is very tough on the patient, he observed—is needed to confirm absence of thrombus.

"It's very cumbersome to organize," he said. "So if it's just a [NOAC] pill and it makes it possible to do cardioversion early, I think it’s a major advantage."

The study was funded by Bayer HealthCare and Janssen Scientific Affairs. Cappato discloses receiving consultancy fees from Boston Scientific, Medtronic, St Jude, Biosense Webster, ELA Sorin, Boehringer Ingelheim, Bayer HealthCare, Abbott, and Pfizer; speaker's bureau fees from Boston Scientific, Medtronic, St Jude, Biosense Webster, BARD, Sanofi, Boehringer Ingelheim, Bayer HealthCare, and Abbott; investigator fees from Medtronic, Biosense Webster, Sanofi, Cameron Health, BARD, Bayer HealthCare, Abbott, and Pfizer; and grants from Boston Scientific, Medtronic, St Jude, Biosense Webster, BARD, and ELA Sorin; he holds equity and intellectual property rights with Cameron Health. Disclosures for the coauthors are listed in the paper.

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