Rivaroxaban shows advantages in AF cardioversion

BARCELONA – Rivaroxaban appears to be a safe and effective alternative to warfarin in patients with atrial fibrillation undergoing elective cardioversion, according to the findings of the first-ever prospective, randomized trial of a novel oral anticoagulant for this application.

Additionally, the X-VeRT trial showed that rivaroxaban (Xarelto) may offer an attractive, highly practical advantage over warfarin, the current guideline-recommended standard of care for cardioversion: Namely, rivaroxaban enabled patients to undergo the procedure more expeditiously, Dr. Riccardo Cappato noted in presenting the X-VeRT findings at the annual congress of the European Society of Cardiology.

Indeed, patients in the early-cardioversion arm of the trial safely underwent the procedure as early as 4 hours after taking their first 20-mg dose of rivaroxaban.

Moreover, patients in the delayed-conversion study arm, which required at least 3 consecutive weeks of effective oral anticoagulation preprocedurally, underwent cardioversion an average of 8 days earlier if randomized to rivaroxaban rather than to warfarin or another vitamin K antagonist. That’s because many warfarin-treated patients couldn’t maintain their international normalized ratio (INR) within the target range of 2.0-3.0 for 3 straight weeks, explained Dr. Cappato, professor of electrophysiology and chief of the arrhythmia and electrophysiology center at the University of Milan’s San Donato Polyclinic Hospital.

X-VeRT included 1,504 patients with nonvalvular atrial fibrillation (AF) at 141 centers in 16 countries. All were scheduled for elective cardioversion. They were randomized 2:1 to rivaroxaban 20 mg once daily or to warfarin at a dose adjusted to maintain an INR of 2.0-3.0.

Of those patients, 872 were assigned to an early-cardioversion strategy. Their cardioversion took place after 1-5 days on study medication, provided transesophageal echocardiography had ruled out a left atrial thrombus or they were already on chronic warfarin with their last three INRs in the target range. The other 632 patients were cardioverted using a delayed strategy in which they had to be on study medication for 3-8 weeks before the procedure.

The primary efficacy outcome in X-VeRT was the composite rate of stroke, TIA, peripheral embolism, MI, and cardiovascular death. The incidence was 0.51% in the rivaroxaban group and not statistically different at 1.02% in the warfarin group. The primary safety outcome – major bleeding – occurred in 0.6% of rivaroxaban-treated patients and 0.8% on warfarin.

The median time to cardioversion in the early-cardioversion strategy arm was similar regardless of which drug was used. Of note, however, in the delayed-strategy group, the median time to cardioversion was 22 days in patients on rivaroxaban, compared with 30 days with warfarin.

Of patients in the delayed-strategy group, 77% of those on rivaroxaban were cardioverted as scheduled, compared with 36% on warfarin. Only one patient in the rivaroxaban group was unable to undergo cardioversion before the 8-week cutoff because of inadequate anticoagulation as defined by less than 80% compliance in pill taking; in contrast, 95 warfarin-treated patients in the delayed-strategy group weren’t cardioverted because they missed the 8-week cutoff because of problematic INRs.

In an interview, ESC spokesman Dr. Jurrien Ten Berg predicted X-VeRT will be practice changing. He believes that on the basis of these study results, many physicians will view elective cardioversion as an excellent time to switch patients from warfarin, with all its inherent problems, to rivaroxaban, especially if they qualify for early cardioversion.

"I think this will absolutely change our policy. Here we’re talking about a once-daily pill that makes it possible to do a cardioversion early, and I think that’s a major advantage. If you delay the cardioversion, anything can happen. We know the vitamin K antagonists are unreliable, especially in the first weeks, when even if the INR is fine you don’t really know if the patient is well anticoagulated. For me, the totally of evidence, including the retrospective analyses of the large atrial fibrillation stroke prevention trials, is enough now to use a NOAC for several days and then do an early cardioversion," said Dr. Ten Berg, a cardiologist at St. Antonius Hospital, Nieuwegein, the Netherlands.

Discussant Dr. Christoph Bode called X-VeRT "a landmark trial" and "brilliant work."

"This should be included in the next update of the guidelines," said Dr. Bode, professor and chair of internal medicine and cardiology at the University of Freiburg, Germany.

However, Dr. Steven Nissen took a more skeptical, albeit clearly a minority, view.

"I think this study shows neither safety nor efficacy for this regimen. There were just a handful of events in both groups, too few to draw any conclusions. I don’t think the guidelines should be changed. I think the proper interpretation of the study is that it’s inconclusive," said Dr. Nissen, chair of the department of cardiovascular medicine at the Cleveland Clinic.

Dr. Cappato noted in response that he’d stated at the outset that X-VeRT, even at more than 1,500 patients, was underpowered statistically. Event rates in well-anticoagulated patients undergoing cardioversion are so low that a study to establish noninferiority for rivaroxaban would require 25,000-30,000 participants, which is not going to happen.

"Many physicians are already switching to NOACs [novel oral anticoagulants] for cardioversion despite the absence of good evidence. We thought bringing forward this solid, methodologically sound information from X-VeRT would provide more consistent support for those who are doing this or considering it," the cardiologist said.

Simultaneous with his presentation in Barcelona, the X-VeRT (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) study was published online (Eur. Heart J. 2014 [doi:10.1093/eurheart/ehu367]).

Dr. Cappato reported receiving investigator fees from and serving as a consultant to and on speakers bureaus for numerous pharmaceutical companies, including Bayer HealthCare, which sponsored X-VeRT. Dr. Bode has received honoraria from Bayer HealthCare. Dr. Ten Berg and Dr. Nissen reported having no financial conflicts.

bjancin@frontlinemedcom.com

BARCELONA – Rivaroxaban appears to be a safe and effective alternative to warfarin in patients with atrial fibrillation undergoing elective cardioversion, according to the findings of the first-ever prospective, randomized trial of a novel oral anticoagulant for this application.

Additionally, the X-VeRT trial showed that rivaroxaban (Xarelto) may offer an attractive, highly practical advantage over warfarin, the current guideline-recommended standard of care for cardioversion: Namely, rivaroxaban enabled patients to undergo the procedure more expeditiously, Dr. Riccardo Cappato noted in presenting the X-VeRT findings at the annual congress of the European Society of Cardiology.

Indeed, patients in the early-cardioversion arm of the trial safely underwent the procedure as early as 4 hours after taking their first 20-mg dose of rivaroxaban.

Moreover, patients in the delayed-conversion study arm, which required at least 3 consecutive weeks of effective oral anticoagulation preprocedurally, underwent cardioversion an average of 8 days earlier if randomized to rivaroxaban rather than to warfarin or another vitamin K antagonist. That’s because many warfarin-treated patients couldn’t maintain their international normalized ratio (INR) within the target range of 2.0-3.0 for 3 straight weeks, explained Dr. Cappato, professor of electrophysiology and chief of the arrhythmia and electrophysiology center at the University of Milan’s San Donato Polyclinic Hospital.

X-VeRT included 1,504 patients with nonvalvular atrial fibrillation (AF) at 141 centers in 16 countries. All were scheduled for elective cardioversion. They were randomized 2:1 to rivaroxaban 20 mg once daily or to warfarin at a dose adjusted to maintain an INR of 2.0-3.0.

Of those patients, 872 were assigned to an early-cardioversion strategy. Their cardioversion took place after 1-5 days on study medication, provided transesophageal echocardiography had ruled out a left atrial thrombus or they were already on chronic warfarin with their last three INRs in the target range. The other 632 patients were cardioverted using a delayed strategy in which they had to be on study medication for 3-8 weeks before the procedure.

The primary efficacy outcome in X-VeRT was the composite rate of stroke, TIA, peripheral embolism, MI, and cardiovascular death. The incidence was 0.51% in the rivaroxaban group and not statistically different at 1.02% in the warfarin group. The primary safety outcome – major bleeding – occurred in 0.6% of rivaroxaban-treated patients and 0.8% on warfarin.

The median time to cardioversion in the early-cardioversion strategy arm was similar regardless of which drug was used. Of note, however, in the delayed-strategy group, the median time to cardioversion was 22 days in patients on rivaroxaban, compared with 30 days with warfarin.

Of patients in the delayed-strategy group, 77% of those on rivaroxaban were cardioverted as scheduled, compared with 36% on warfarin. Only one patient in the rivaroxaban group was unable to undergo cardioversion before the 8-week cutoff because of inadequate anticoagulation as defined by less than 80% compliance in pill taking; in contrast, 95 warfarin-treated patients in the delayed-strategy group weren’t cardioverted because they missed the 8-week cutoff because of problematic INRs.

In an interview, ESC spokesman Dr. Jurrien Ten Berg predicted X-VeRT will be practice changing. He believes that on the basis of these study results, many physicians will view elective cardioversion as an excellent time to switch patients from warfarin, with all its inherent problems, to rivaroxaban, especially if they qualify for early cardioversion.

"I think this will absolutely change our policy. Here we’re talking about a once-daily pill that makes it possible to do a cardioversion early, and I think that’s a major advantage. If you delay the cardioversion, anything can happen. We know the vitamin K antagonists are unreliable, especially in the first weeks, when even if the INR is fine you don’t really know if the patient is well anticoagulated. For me, the totally of evidence, including the retrospective analyses of the large atrial fibrillation stroke prevention trials, is enough now to use a NOAC for several days and then do an early cardioversion," said Dr. Ten Berg, a cardiologist at St. Antonius Hospital, Nieuwegein, the Netherlands.

Discussant Dr. Christoph Bode called X-VeRT "a landmark trial" and "brilliant work."

"This should be included in the next update of the guidelines," said Dr. Bode, professor and chair of internal medicine and cardiology at the University of Freiburg, Germany.

However, Dr. Steven Nissen took a more skeptical, albeit clearly a minority, view.

"I think this study shows neither safety nor efficacy for this regimen. There were just a handful of events in both groups, too few to draw any conclusions. I don’t think the guidelines should be changed. I think the proper interpretation of the study is that it’s inconclusive," said Dr. Nissen, chair of the department of cardiovascular medicine at the Cleveland Clinic.

Dr. Cappato noted in response that he’d stated at the outset that X-VeRT, even at more than 1,500 patients, was underpowered statistically. Event rates in well-anticoagulated patients undergoing cardioversion are so low that a study to establish noninferiority for rivaroxaban would require 25,000-30,000 participants, which is not going to happen.

"Many physicians are already switching to NOACs [novel oral anticoagulants] for cardioversion despite the absence of good evidence. We thought bringing forward this solid, methodologically sound information from X-VeRT would provide more consistent support for those who are doing this or considering it," the cardiologist said.

Simultaneous with his presentation in Barcelona, the X-VeRT (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) study was published online (Eur. Heart J. 2014 [doi:10.1093/eurheart/ehu367]).

Dr. Cappato reported receiving investigator fees from and serving as a consultant to and on speakers bureaus for numerous pharmaceutical companies, including Bayer HealthCare, which sponsored X-VeRT. Dr. Bode has received honoraria from Bayer HealthCare. Dr. Ten Berg and Dr. Nissen reported having no financial conflicts.

bjancin@frontlinemedcom.com

BARCELONA – Rivaroxaban appears to be a safe and effective alternative to warfarin in patients with atrial fibrillation undergoing elective cardioversion, according to the findings of the first-ever prospective, randomized trial of a novel oral anticoagulant for this application.

Additionally, the X-VeRT trial showed that rivaroxaban (Xarelto) may offer an attractive, highly practical advantage over warfarin, the current guideline-recommended standard of care for cardioversion: Namely, rivaroxaban enabled patients to undergo the procedure more expeditiously, Dr. Riccardo Cappato noted in presenting the X-VeRT findings at the annual congress of the European Society of Cardiology.

Indeed, patients in the early-cardioversion arm of the trial safely underwent the procedure as early as 4 hours after taking their first 20-mg dose of rivaroxaban.

Moreover, patients in the delayed-conversion study arm, which required at least 3 consecutive weeks of effective oral anticoagulation preprocedurally, underwent cardioversion an average of 8 days earlier if randomized to rivaroxaban rather than to warfarin or another vitamin K antagonist. That’s because many warfarin-treated patients couldn’t maintain their international normalized ratio (INR) within the target range of 2.0-3.0 for 3 straight weeks, explained Dr. Cappato, professor of electrophysiology and chief of the arrhythmia and electrophysiology center at the University of Milan’s San Donato Polyclinic Hospital.

X-VeRT included 1,504 patients with nonvalvular atrial fibrillation (AF) at 141 centers in 16 countries. All were scheduled for elective cardioversion. They were randomized 2:1 to rivaroxaban 20 mg once daily or to warfarin at a dose adjusted to maintain an INR of 2.0-3.0.

Of those patients, 872 were assigned to an early-cardioversion strategy. Their cardioversion took place after 1-5 days on study medication, provided transesophageal echocardiography had ruled out a left atrial thrombus or they were already on chronic warfarin with their last three INRs in the target range. The other 632 patients were cardioverted using a delayed strategy in which they had to be on study medication for 3-8 weeks before the procedure.

The primary efficacy outcome in X-VeRT was the composite rate of stroke, TIA, peripheral embolism, MI, and cardiovascular death. The incidence was 0.51% in the rivaroxaban group and not statistically different at 1.02% in the warfarin group. The primary safety outcome – major bleeding – occurred in 0.6% of rivaroxaban-treated patients and 0.8% on warfarin.

The median time to cardioversion in the early-cardioversion strategy arm was similar regardless of which drug was used. Of note, however, in the delayed-strategy group, the median time to cardioversion was 22 days in patients on rivaroxaban, compared with 30 days with warfarin.

Of patients in the delayed-strategy group, 77% of those on rivaroxaban were cardioverted as scheduled, compared with 36% on warfarin. Only one patient in the rivaroxaban group was unable to undergo cardioversion before the 8-week cutoff because of inadequate anticoagulation as defined by less than 80% compliance in pill taking; in contrast, 95 warfarin-treated patients in the delayed-strategy group weren’t cardioverted because they missed the 8-week cutoff because of problematic INRs.

In an interview, ESC spokesman Dr. Jurrien Ten Berg predicted X-VeRT will be practice changing. He believes that on the basis of these study results, many physicians will view elective cardioversion as an excellent time to switch patients from warfarin, with all its inherent problems, to rivaroxaban, especially if they qualify for early cardioversion.

"I think this will absolutely change our policy. Here we’re talking about a once-daily pill that makes it possible to do a cardioversion early, and I think that’s a major advantage. If you delay the cardioversion, anything can happen. We know the vitamin K antagonists are unreliable, especially in the first weeks, when even if the INR is fine you don’t really know if the patient is well anticoagulated. For me, the totally of evidence, including the retrospective analyses of the large atrial fibrillation stroke prevention trials, is enough now to use a NOAC for several days and then do an early cardioversion," said Dr. Ten Berg, a cardiologist at St. Antonius Hospital, Nieuwegein, the Netherlands.

Discussant Dr. Christoph Bode called X-VeRT "a landmark trial" and "brilliant work."

"This should be included in the next update of the guidelines," said Dr. Bode, professor and chair of internal medicine and cardiology at the University of Freiburg, Germany.

However, Dr. Steven Nissen took a more skeptical, albeit clearly a minority, view.

"I think this study shows neither safety nor efficacy for this regimen. There were just a handful of events in both groups, too few to draw any conclusions. I don’t think the guidelines should be changed. I think the proper interpretation of the study is that it’s inconclusive," said Dr. Nissen, chair of the department of cardiovascular medicine at the Cleveland Clinic.

Dr. Cappato noted in response that he’d stated at the outset that X-VeRT, even at more than 1,500 patients, was underpowered statistically. Event rates in well-anticoagulated patients undergoing cardioversion are so low that a study to establish noninferiority for rivaroxaban would require 25,000-30,000 participants, which is not going to happen.

"Many physicians are already switching to NOACs [novel oral anticoagulants] for cardioversion despite the absence of good evidence. We thought bringing forward this solid, methodologically sound information from X-VeRT would provide more consistent support for those who are doing this or considering it," the cardiologist said.

Simultaneous with his presentation in Barcelona, the X-VeRT (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) study was published online (Eur. Heart J. 2014 [doi:10.1093/eurheart/ehu367]).

Dr. Cappato reported receiving investigator fees from and serving as a consultant to and on speakers bureaus for numerous pharmaceutical companies, including Bayer HealthCare, which sponsored X-VeRT. Dr. Bode has received honoraria from Bayer HealthCare. Dr. Ten Berg and Dr. Nissen reported having no financial conflicts.

bjancin@frontlinemedcom.com