In a real-world analysis involving more than 11,000 patients with atrial fibrillation from 47 countries, the risk for stroke and major bleeding in users of the direct oral anticoagulant Xarelto (rivaroxaban) was similar to or lower than that seen in the pivotal clinical trials, researchers report.
The one-year rate of stroke or systemic embolism was only 1.0% and the rate of major bleeding was 1.7% in the large, pre-planned pooled analysis of three previously described prospective, observational, international, non-interventional studies that comprised the XANTUS program.
"Overall, rivaroxaban showed a favorable safety profile, with greater than 96% of the pooled rivaroxaban population not experiencing any of the events of treatment-emergent major bleeding, stroke/non-CNS systemic embolism (SE) or all-cause death over a follow-up period of approximately one year," wrote Paulus Kirchhof, MD, of the University of Birmingham in England, and colleagues in the Journal of the American College of Cardiology, published online July 2.
The researchers noted that the XANTUS program offers a unique source of real-world data on the use of rivaroxaban for stroke prevention in Afib patients. The three prospective studies included patients from Western and Eastern Europe, Canada and Israel (XANTUS trial), the Asia-Pacific region (XANAP trial), and Eastern Europe the Middle East, Africa and Latin America (XANTUS-EL).
Patients were prescribed the direct oral anticoagulant (DOAC) rivaroxaban in accordance with country-specific drug approvals.
Primary outcomes were treatment-emergent major bleeding, adverse events (AEs)/serious AEs, and all-cause death. Secondary outcomes included treatment-emergent thromboembolic events and non-major bleeding.
Overall, 11,121 patients were included in the analysis (mean age 70.5±10.5 years; female 42.9%). Comorbidities included heart failure (21.2%), hypertension (76.2%), and diabetes (22.3%).
Event rates, calculated as one event per 100 patient-years, were:
- Major bleeding: 1.7/100 patient-years; 95% CI 1.5-2.0)
- All-cause death: 1.9/100 patient-years (95% CI 1.6-2.2)
- Stroke or systemic embolism: 1.0/100 patient-years (95% CI 0.8 to 1.2)
Regional differences were considerable. For instance, major bleeding rates varied from 0.7 per 100 patient-years in Latin America verses 2.3 per 100 patient-years in a group including Western Europe, Canada, and Israel.
One-year treatment persistence was 77.4%, with East Asia showing the lowest rate (66.4%) and Eastern Europe the highest (84.4%).
The researchers concluded that the real-world treatment analysis showed low bleeding and stroke rates in rivaroxaban-treated patients with Afib. Low rates of treatment discontinuation were seen throughout the world and results were broadly consistent across regions.
Study limitations cited by the researchers included the exclusion of patients from the United States and China (with the exception of Hong Kong) from the analysis and possible selection bias, given that patients had to agree to participate in the study.
In an accompanying editorial, cardiologist Jeff Healey, MD, of McMaster University in Hamilton, Ontario, noted that the study population was very representative of the practices they came from.
"The age and the proportion of patients with hypertension, diabetes and prior stroke in this cohort are quite similar to another multinational registry enrolling patients from the emergency department, suggesting that these patients are reasonably representative of the larger population of individuals with AF," he wrote. "Thus, like may observational studies, the current study population is a reasonable balance of what is practical and what is ideal."
Kirchhof and colleagues noted that the patients included in the observational studies had similar characteristics to those included in the clinical trials.
Healey wrote that the analysis confirms that "the use of rivaroxaban is largely in accordance with published guidelines, and persistence with therapy at one year was high, at least in the practices of participating physicians."
"Although these data are not population-based, they represent what a typical clinician might expect if they utilize a DOAC medication in accordance with local product labeling and practice guidelines, and are a testament to the successful introduction of DOACs into the clinical practice," Healey wrote.
"Although the current work does not help us to understand why the translation into clinical practice was so successful, easy-to-use medications, clear high-quality randomized trials, thoughtful practice guidelines, and coordinated physician education all likely played a role."
The XANTUS resarch program was funded by Bayer.
Paulus Kirchhof has received research support from Bayer HealthCare, AstraZeneca, Bioscnece Webster, Boehringer Ingelheim and other pharmaceutical companies.
Journal of the American College of Cardiology
Source Reference: Kirchhof P, et al "Global prospective safety analysis of rivaroxaban" JACC 2018; DOI: j.jacc.2018.04.058.
Journal of the American College of Cardiology
Source Reference: Healey JS "Stroke prevention in atrial fibrillation: what real world and what do real-world data reveal?" JACC 2018; DOI: 10.1016/j.jacc.2018.04.057.
Read the original article on Medpage Today: Real-World Xarelto Data Show Stroke, Bleeding Risk Low