Studying Rivaroxaban’s Safety in Real-World Settings

LONDON—Rivaroxaban was associated with low rates of bleeding and stroke in two observational studies that included more than 45,000 patients, according to safety data presented at the 2015 European Society of Cardiology Congress. The findings show that the safety profile of the factor Xa inhibitor, when used in the routine care of patients with nonvalvular atrial fibrillation, is consistent with the safety profile observed in a pivotal phase III trial, researchers said. In addition, new safety data comparing rivaroxaban (marketed as Xarelto), apixaban (Eliquis) and dabigatran (Pradaxa) provide insights on the use of these stroke prevention therapies in real-world settings.

Observational Studies

The Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation (XANTUS) study involved 6,784 individuals treated at centers in Europe, Canada, and Israel. The incidence of major bleeding was 2.1% per year and the rate of stroke was 0.7% per year. Rates of fatal, critical organ, and intracranial bleeding were 0.2%, 0.7%, and 0.4% per year, 
respectively.

“The rates of stroke and systemic embolism, all strokes, and gastrointestinal bleeding were markedly lower in XANTUS in comparison to [the phase III trial] ROCKET AF,” said John Camm, MD, Professor of Clinical Cardiology at St. George’s Hospital in London, who presented the XANTUS study findings. Dr. Camm noted that XANTUS study and ROCKET AF had different patient populations and designs. Patients in the single-arm, prospective, observational XANTUS study were recruited from routine primary care practices and had an overall lower risk of stroke than those enrolled in the randomized, double-blind, controlled clinical trial who were at more moderate to high risk, with respective CHADS2 scores of 2.0 and 3.5.

The findings of the XANTUS study, which were published online in European Heart Journal, highlight the “real-world” safety of rivaroxaban, Dr. Camm said. “These real-world insights from XANTUS complement and expand on what we already know from clinical trials and provide physicians with reassurance to prescribe rivaroxaban as an effective and well-tolerated treatment option for the broad range of patients with atrial fibrillation seen in their everyday practice,” he said.

Postmarketing Safety Surveillance

Similar results from a separate postmarketing safety surveillance (PMSS) study of rivaroxaban also were reported at the meeting. The study is an ongoing, retrospective, five-year, observational study of more than 39,000 patients with nonvalvular atrial fibrillation in the United States. At two years, the incidence of major bleeding was 2.89% per year and the incidence of fatal bleeding was 0.1% per year.

“Real-world research is an essential complement to clinical trials and helps inform treatment decisions,” said study investigator W. Frank Peacock, MD, Associate Chair and Research Director of Emergency Medicine at Baylor College of Medicine in Houston. “These studies confirm the safety profile of rivaroxaban in real-world settings around the globe.”

The XANTUS and PMSS studies are part of a large postlicensing program and were respectively designed to meet European Medicines Agency and FDA requirements on the long-term monitoring of medicines. Researchers are conducting similar studies in other regions.

Comparing Therapies

Investigators also presented data gleaned from electronic medical records comparing the potential bleeding risks of the factor Xa inhibitor apixaban versus other available non–vitamin K antagonists, including rivaroxaban and the direct thrombin inhibitor dabigatran. Gregory Lip, MD, Professor of Cardiovascular Medicine at the University of Birmingham in the United Kingdom, and colleagues reported data from retrospective analyses of different US electronic medical records of patients with nonvalvular atrial fibrillation newly started on a novel oral anticoagulant (NOAC) or warfarin in 2013 or 2014. In two studies, most patients were started on warfarin (43.3% and 69.6%), followed by rivaroxaban (34.3% and 17.9%), dabigatran (14.2% and 6.8%), and apixaban (8.2% and 5.7%).

In one study of 29,338 patients using a commercial and Medicare supplemental database, those newly starting treatment with an NOAC had significantly lower rates of major bleeding than those starting treatment with warfarin (4.6% per year for warfarin vs 2.35% per year for apixiban, 3.38% per year for dabigatran, and 4.57% per year for rivaroxaban).

In a study of 35,757 patients using Humedica electronic health record data, the respective adjusted hazard ratios for bleeding risk were 1.094, 0.747 and 0.679, comparing rivaroxaban, apixaban, and dabigatran versus warfarin.

A study by Steven Deitelzweig, MD, Chair of Hospital Medicine at Ochsner Medical Center in New Orleans, and colleagues suggested that apixaban was associated with fewer bleeding-related hospital readmissions than either rivaroxaban or dabigatran in hospitalized patients with nonvalvular atrial fibrillation.Dr. Lip also presented six-month follow-up data on more than 60,000 patients with nonvalvular atrial fibrillation who were treated with one of the three NOACs. The researchers analyzed data from a US medical claims database. Most of the patients (50.6%) were treated with rivaroxaban, 34.8% were treated with dabigatran, and 14.6% were treated with apixaban. Unadjusted data showed that the rates of major bleeding were 20.2% per year, 13.2% per year, and 14.5% per year, respectively.

Dr. Lip observed that, after adjusting the data, patients taking dabigatran had higher rates of clinically relevant nonmajor gastrointestinal bleeding (hazard ratio [HR], 1.24) and that those taking rivaroxaban were more likely to have major (HR, 3.6), clinically relevant nonmajor (HR, 1.43), or any bleeding (HR, 1.41) when compared with those taking apixaban. “Larger cohort studies and longer follow-up data of general nonvalvular atrial fibrillation populations will be needed to confirm these early observations,” he concluded.

Informing Clinical Practice

While real-world research has limitations and cannot replace clinical trial findings as a means to compare the clinical efficacy or safety profiles of various medicines, such studies can help inform clinical practice, said Dr. Camm.

“With 10 million people in Europe alone affected by atrial fibrillation, a number that is only expected to increase, real-world insights on routine anticoagulation management in everyday clinical practice are increasingly important for physicians and patients,” he said.

—Sara Freeman

LONDON—Rivaroxaban was associated with low rates of bleeding and stroke in two observational studies that included more than 45,000 patients, according to safety data presented at the 2015 European Society of Cardiology Congress. The findings show that the safety profile of the factor Xa inhibitor, when used in the routine care of patients with nonvalvular atrial fibrillation, is consistent with the safety profile observed in a pivotal phase III trial, researchers said. In addition, new safety data comparing rivaroxaban (marketed as Xarelto), apixaban (Eliquis) and dabigatran (Pradaxa) provide insights on the use of these stroke prevention therapies in real-world settings.

Observational Studies

The Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation (XANTUS) study involved 6,784 individuals treated at centers in Europe, Canada, and Israel. The incidence of major bleeding was 2.1% per year and the rate of stroke was 0.7% per year. Rates of fatal, critical organ, and intracranial bleeding were 0.2%, 0.7%, and 0.4% per year, 
respectively.

“The rates of stroke and systemic embolism, all strokes, and gastrointestinal bleeding were markedly lower in XANTUS in comparison to [the phase III trial] ROCKET AF,” said John Camm, MD, Professor of Clinical Cardiology at St. George’s Hospital in London, who presented the XANTUS study findings. Dr. Camm noted that XANTUS study and ROCKET AF had different patient populations and designs. Patients in the single-arm, prospective, observational XANTUS study were recruited from routine primary care practices and had an overall lower risk of stroke than those enrolled in the randomized, double-blind, controlled clinical trial who were at more moderate to high risk, with respective CHADS2 scores of 2.0 and 3.5.

The findings of the XANTUS study, which were published online in European Heart Journal, highlight the “real-world” safety of rivaroxaban, Dr. Camm said. “These real-world insights from XANTUS complement and expand on what we already know from clinical trials and provide physicians with reassurance to prescribe rivaroxaban as an effective and well-tolerated treatment option for the broad range of patients with atrial fibrillation seen in their everyday practice,” he said.

Postmarketing Safety Surveillance

Similar results from a separate postmarketing safety surveillance (PMSS) study of rivaroxaban also were reported at the meeting. The study is an ongoing, retrospective, five-year, observational study of more than 39,000 patients with nonvalvular atrial fibrillation in the United States. At two years, the incidence of major bleeding was 2.89% per year and the incidence of fatal bleeding was 0.1% per year.

“Real-world research is an essential complement to clinical trials and helps inform treatment decisions,” said study investigator W. Frank Peacock, MD, Associate Chair and Research Director of Emergency Medicine at Baylor College of Medicine in Houston. “These studies confirm the safety profile of rivaroxaban in real-world settings around the globe.”

The XANTUS and PMSS studies are part of a large postlicensing program and were respectively designed to meet European Medicines Agency and FDA requirements on the long-term monitoring of medicines. Researchers are conducting similar studies in other regions.

Comparing Therapies

Investigators also presented data gleaned from electronic medical records comparing the potential bleeding risks of the factor Xa inhibitor apixaban versus other available non–vitamin K antagonists, including rivaroxaban and the direct thrombin inhibitor dabigatran. Gregory Lip, MD, Professor of Cardiovascular Medicine at the University of Birmingham in the United Kingdom, and colleagues reported data from retrospective analyses of different US electronic medical records of patients with nonvalvular atrial fibrillation newly started on a novel oral anticoagulant (NOAC) or warfarin in 2013 or 2014. In two studies, most patients were started on warfarin (43.3% and 69.6%), followed by rivaroxaban (34.3% and 17.9%), dabigatran (14.2% and 6.8%), and apixaban (8.2% and 5.7%).

In one study of 29,338 patients using a commercial and Medicare supplemental database, those newly starting treatment with an NOAC had significantly lower rates of major bleeding than those starting treatment with warfarin (4.6% per year for warfarin vs 2.35% per year for apixiban, 3.38% per year for dabigatran, and 4.57% per year for rivaroxaban).

In a study of 35,757 patients using Humedica electronic health record data, the respective adjusted hazard ratios for bleeding risk were 1.094, 0.747 and 0.679, comparing rivaroxaban, apixaban, and dabigatran versus warfarin.

A study by Steven Deitelzweig, MD, Chair of Hospital Medicine at Ochsner Medical Center in New Orleans, and colleagues suggested that apixaban was associated with fewer bleeding-related hospital readmissions than either rivaroxaban or dabigatran in hospitalized patients with nonvalvular atrial fibrillation.Dr. Lip also presented six-month follow-up data on more than 60,000 patients with nonvalvular atrial fibrillation who were treated with one of the three NOACs. The researchers analyzed data from a US medical claims database. Most of the patients (50.6%) were treated with rivaroxaban, 34.8% were treated with dabigatran, and 14.6% were treated with apixaban. Unadjusted data showed that the rates of major bleeding were 20.2% per year, 13.2% per year, and 14.5% per year, respectively.

Dr. Lip observed that, after adjusting the data, patients taking dabigatran had higher rates of clinically relevant nonmajor gastrointestinal bleeding (hazard ratio [HR], 1.24) and that those taking rivaroxaban were more likely to have major (HR, 3.6), clinically relevant nonmajor (HR, 1.43), or any bleeding (HR, 1.41) when compared with those taking apixaban. “Larger cohort studies and longer follow-up data of general nonvalvular atrial fibrillation populations will be needed to confirm these early observations,” he concluded.

Informing Clinical Practice

While real-world research has limitations and cannot replace clinical trial findings as a means to compare the clinical efficacy or safety profiles of various medicines, such studies can help inform clinical practice, said Dr. Camm.

“With 10 million people in Europe alone affected by atrial fibrillation, a number that is only expected to increase, real-world insights on routine anticoagulation management in everyday clinical practice are increasingly important for physicians and patients,” he said.

—Sara Freeman

LONDON—Rivaroxaban was associated with low rates of bleeding and stroke in two observational studies that included more than 45,000 patients, according to safety data presented at the 2015 European Society of Cardiology Congress. The findings show that the safety profile of the factor Xa inhibitor, when used in the routine care of patients with nonvalvular atrial fibrillation, is consistent with the safety profile observed in a pivotal phase III trial, researchers said. In addition, new safety data comparing rivaroxaban (marketed as Xarelto), apixaban (Eliquis) and dabigatran (Pradaxa) provide insights on the use of these stroke prevention therapies in real-world settings.

Observational Studies

The Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation (XANTUS) study involved 6,784 individuals treated at centers in Europe, Canada, and Israel. The incidence of major bleeding was 2.1% per year and the rate of stroke was 0.7% per year. Rates of fatal, critical organ, and intracranial bleeding were 0.2%, 0.7%, and 0.4% per year, 
respectively.

“The rates of stroke and systemic embolism, all strokes, and gastrointestinal bleeding were markedly lower in XANTUS in comparison to [the phase III trial] ROCKET AF,” said John Camm, MD, Professor of Clinical Cardiology at St. George’s Hospital in London, who presented the XANTUS study findings. Dr. Camm noted that XANTUS study and ROCKET AF had different patient populations and designs. Patients in the single-arm, prospective, observational XANTUS study were recruited from routine primary care practices and had an overall lower risk of stroke than those enrolled in the randomized, double-blind, controlled clinical trial who were at more moderate to high risk, with respective CHADS2 scores of 2.0 and 3.5.

The findings of the XANTUS study, which were published online in European Heart Journal, highlight the “real-world” safety of rivaroxaban, Dr. Camm said. “These real-world insights from XANTUS complement and expand on what we already know from clinical trials and provide physicians with reassurance to prescribe rivaroxaban as an effective and well-tolerated treatment option for the broad range of patients with atrial fibrillation seen in their everyday practice,” he said.

Postmarketing Safety Surveillance

Similar results from a separate postmarketing safety surveillance (PMSS) study of rivaroxaban also were reported at the meeting. The study is an ongoing, retrospective, five-year, observational study of more than 39,000 patients with nonvalvular atrial fibrillation in the United States. At two years, the incidence of major bleeding was 2.89% per year and the incidence of fatal bleeding was 0.1% per year.

“Real-world research is an essential complement to clinical trials and helps inform treatment decisions,” said study investigator W. Frank Peacock, MD, Associate Chair and Research Director of Emergency Medicine at Baylor College of Medicine in Houston. “These studies confirm the safety profile of rivaroxaban in real-world settings around the globe.”

The XANTUS and PMSS studies are part of a large postlicensing program and were respectively designed to meet European Medicines Agency and FDA requirements on the long-term monitoring of medicines. Researchers are conducting similar studies in other regions.

Comparing Therapies

Investigators also presented data gleaned from electronic medical records comparing the potential bleeding risks of the factor Xa inhibitor apixaban versus other available non–vitamin K antagonists, including rivaroxaban and the direct thrombin inhibitor dabigatran. Gregory Lip, MD, Professor of Cardiovascular Medicine at the University of Birmingham in the United Kingdom, and colleagues reported data from retrospective analyses of different US electronic medical records of patients with nonvalvular atrial fibrillation newly started on a novel oral anticoagulant (NOAC) or warfarin in 2013 or 2014. In two studies, most patients were started on warfarin (43.3% and 69.6%), followed by rivaroxaban (34.3% and 17.9%), dabigatran (14.2% and 6.8%), and apixaban (8.2% and 5.7%).

In one study of 29,338 patients using a commercial and Medicare supplemental database, those newly starting treatment with an NOAC had significantly lower rates of major bleeding than those starting treatment with warfarin (4.6% per year for warfarin vs 2.35% per year for apixiban, 3.38% per year for dabigatran, and 4.57% per year for rivaroxaban).

In a study of 35,757 patients using Humedica electronic health record data, the respective adjusted hazard ratios for bleeding risk were 1.094, 0.747 and 0.679, comparing rivaroxaban, apixaban, and dabigatran versus warfarin.

A study by Steven Deitelzweig, MD, Chair of Hospital Medicine at Ochsner Medical Center in New Orleans, and colleagues suggested that apixaban was associated with fewer bleeding-related hospital readmissions than either rivaroxaban or dabigatran in hospitalized patients with nonvalvular atrial fibrillation.Dr. Lip also presented six-month follow-up data on more than 60,000 patients with nonvalvular atrial fibrillation who were treated with one of the three NOACs. The researchers analyzed data from a US medical claims database. Most of the patients (50.6%) were treated with rivaroxaban, 34.8% were treated with dabigatran, and 14.6% were treated with apixaban. Unadjusted data showed that the rates of major bleeding were 20.2% per year, 13.2% per year, and 14.5% per year, respectively.

Dr. Lip observed that, after adjusting the data, patients taking dabigatran had higher rates of clinically relevant nonmajor gastrointestinal bleeding (hazard ratio [HR], 1.24) and that those taking rivaroxaban were more likely to have major (HR, 3.6), clinically relevant nonmajor (HR, 1.43), or any bleeding (HR, 1.41) when compared with those taking apixaban. “Larger cohort studies and longer follow-up data of general nonvalvular atrial fibrillation populations will be needed to confirm these early observations,” he concluded.

Informing Clinical Practice

While real-world research has limitations and cannot replace clinical trial findings as a means to compare the clinical efficacy or safety profiles of various medicines, such studies can help inform clinical practice, said Dr. Camm.

“With 10 million people in Europe alone affected by atrial fibrillation, a number that is only expected to increase, real-world insights on routine anticoagulation management in everyday clinical practice are increasingly important for physicians and patients,” he said.

—Sara Freeman