Across populations, rivaroxaban reduces stroke, bleeding risk in AF

Patients with atrial fibrillation who were treated with rivaroxaban had a reduced risk for bleeding events and stroke, in addition to low treatment continuation rates, according to an analysis published in the Journal of the American College of Cardiology.

“The results were consistent across different regions and patient populations worldwide, based on each of the individual rivaroxaban studies, and further expand the body of evidence on the safety of patients with AF receiving rivaroxaban for stroke prevention,” Paulus Kirchhof, MD, director of the Institute of Cardiovascular Sciences and chair in cardiovascular medicine at University of Birmingham in the United Kingdom, and colleagues wrote.

XANTUS registries

Researchers performed a preplanned pooled analysis of data of 11,121 patients (mean age, 71 years; 43% women) with AF from the XANTUS, XANAP and XANTUS-EL registries. These patients were from 47 countries across five regions of the world and were treated with rivaroxaban (Xarelto, Janssen) for the prevention of stroke or noncentral nervous system systemic embolism.

Patients in all registries were prescribed rivaroxaban based on drug approvals from the countries they lived in. Those with creatinine clearance greater than 50 mL per minute were given 20 mg rivaroxaban once per day, whereas patients with creatinine clearance less than 50 mL per minute were prescribed 15 mg rivaroxaban once per day. Patients from Taiwan were prescribed 15 mg or 20 mg rivaroxaban once per day if the creatinine clearance was greater than 50 mL per minute, and those with a clearance between 15 mL per minute and 50 mL per minute were given 10 mg or 15 mg of rivaroxaban once per day.

Follow-up was conducted for up to 1 year or for greater than 30 days for those who permanently discontinued rivaroxaban.

Primary outcomes were related to the safety of rivaroxaban, including serious adverse events or treatment-emergent adverse events. Secondary outcomes included nonmajor bleeding, symptomatic thromboembolic events, treatment persistence, treatment satisfaction and reasons for treatment interruption.

Patients had comorbidities that were associated with stroke and/or bleeding events, including hypertension (76.2%), congestive HF (21.2%) and diabetes (22.3%).

The event rate was 1.7 per 100 patient-years for major bleeding (95% CI, 1.5-2), with the lowest rates seen in Latin America (0.7 per 100 patient-years) and the highest in Western Europe, Canada and Israel (2.3 per 100 patient-years). The event rate for all-cause death was 1.9 per 100 patient-years (95% CI, 1.6-2.2), with the highest rate in Latin American, Middle East and Africa (2.7 per 100 patient-years) and the lowest rate in Eastern Europe (1.5 per 100 patient-years).

In all patients, the event rate for stroke or systolic embolism was 1 per 100 person-years (95% CI, 0.8-1.2). The highest rate was seen in East Asia (1.8 per 100 patient-years) and the lowest was in Latin America (0 per 100 patient-years).

Continued treatment

Treatment persistence at 1 year was 77.4%, with the highest percentage in Eastern Europe (84.4%) and the lowest in East Asia (66.4%).

“The finding that overall rates of major outcomes increased with decreasing rivaroxaban dose received suggests that patients with an on-label recommendation to receive a reduced rivaroxaban dose may be of poorer health and more prone to [adverse events] than patients who are label-recommended to receive the standard rivaroxaban dose,” Kirchhof and colleagues wrote.

“Although these data are not population-based, they represent what a typical clinician might expect if they utilize a [direct oral anticoagulant] medication in accordance with local product labeling and practice guidelines and are a testament to the successful introduction of [direct oral anticoagulants] into the clinical practice,” Jeff S. Healey, MD, MSc, director of arrhythmia services and associate professor of medicine at McMaster University in Hamilton, Ontario, Canada, wrote in a related editorial. “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.” – by Darlene Dobkowski

Disclosure s : The XANTUS research program was funded by Bayer. Kirchhof reports he received research support from 3M Medica, AstraZeneca, Bayer HealthCare, Biosense Webster, Boehringer Ingelheim, the British Heart Foundation, Daiichi-Sankyo, the European Union, German Cardiac Society, the German Centre for Cardiovascular Research, the Leducq Foundation, MEDA Pharma, the Medical Research Council (U.K.), Medtronic, Merck Sharp & Dohme, Otsuka Pharma, Pfizer/Bristol-Myers Squibb, Sanofi, Servier, Siemens, and Takeda; received honoraria from several such companies, and is listed as an inventor on two pending patents held by the University of Birmingham. Healey reports he received research grants from Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer and speaker fees from Bayer, Bristol-Myers Squibb, Pfizer and Servier. Please see the study for all other authors’ relevant financial disclosures.