Rivaroxaban in Patients with Atrial Fibrillation Undergoing Cardioversion

A novel oral anticoagulant’s trial performance has led European regulators to approve its use in cardioversion for patients with atrial fibrillation (AF).

Researchers compared rivaroxaban (Xarelto) against vitamin K antagonist anticoagulants such as warfarin in 1,504 patients who received cardioversion to restore heart rhythm.

The 978 patients who received rivaroxaban actually fared far better than the 492 who received vitamin K antagonists, but the study team warned in the European Heart Journal that the trial was "underpowered to provide statistically rigorous results and was thus exploratory in nature."

The trial was large enough, however, to convince the European Medicines Agency that rivaroxaban works in conjunction with cardioversion well enough to make it a viable alternative to vitamin K antagonists — and possibly much better.

Rivaroxaban patients were just half as likely as control group patients to suffer stroke, transient ischemic attack, peripheral embolism, MI, or cardiovascular death during the follow-up period (95% confidence interval [CI], 0.15—1.73). Rivaroxaban was also associated with a less major bleeding than vitamin K antagonists (relative risk, 0.76; 95% CI (0.21–2.67).

In addition to suggesting that cardioversion patients fare better with rivaroxaban than they fare with vitamin K antagonists, the trial also indicated the new drug enjoys at least 1 other advantage over its older rivals: speed.

Patients who received rivaroxaban and patients who received vitamin K antagonists during the trial were both spilt into 2 groups. The first underwent cardioversion after just 1 to 5 days of anticoagulation. The second received treatment only after 3 weeks of effective anticoagulation.

In that second group, when treatment hinged on sustained anticoagulation, the average time-to-procedure was far shorter among patients who received the novel anticoagulant rather than a vitamin K antagonist.

Rivaroxaban worked more consistently than vitamin K antagonists, so it took less time, on average, for patients to experience 3 straight weeks of effective anticoagulants. Indeed, 77% of those in the 3-week rivaroxaban group but only 36% in the control group underwent cardioversion within 8 weeks of enrollment.

"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 co-principal investigator Riccardo Cappato, MD, in a news release.

Treatment within 8 weeks was not among the initial endpoints of the trial, but European regulators thought the finding constituted such a practical advantage for rivaroxaban that they decided to include the data on the explanatory notes that accompany the drug’s new indication.

"The Xarelto label update provides physicians with clear guidance for patients with atrial fibrillation undergoing cardioversion,” Cappato said. “The X-VeRT study showed Xarelto to be an effective and well-tolerated alternative to vitamin K antagonists with a practical advantage over VKAs."

Cappato also said that while real-world use may eventually provide statistically definitive information about the relative risks of rivaroxaban and warfarin for patients who undergo cardioversion, definitive trials are unlikely. Such trials would require at least 10 times as many patients and thus cost a prohibitive amount.

The rivaroxaban-cardioveration trial was the first prospective effort to compare any of the novel oral anticoagulants with drugs like warfarin in AF patients who received cardioversion. Some analysts believe the trial, and the approval it triggered, may help rivaroxaban gain market share against similar drugs such as dabigatran (Pradaxa), apixaban (Eliquis), and edoxaban (Savaysa).