LONDON – The factor Xa inhibitor rivaroxaban was associated with low rates of bleeding and stroke in two observational studies that included more than 45,000 people with nonvalvular atrial fibrillation.
The XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) 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 risk of stroke was 0.7% per year. Rates of fatal, critical organ, and intracranial bleeding were also low at 0.2%, 0.7%, and 0.4% per year, respectively.
Sara Freeman/Frontline Medical News
Dr. John Camm
“The rates of stroke and systemic embolism, all strokes and gastrointestinal bleeding were markedly lower in XANTUS in comparison to ROCKET-AF,” noted Dr. John Camm who presented the XANTUS study findings at the annual congress of the European Society of Cardiology. “Major bleeding was also largely reduced in XANTUS, however the death rate and intracranial hemorrhage rate was similar,” he added.
Dr. Camm, who is professor of clinical cardiology at St George’s Hospital in London, noted that the patient populations and the design of the XANTUS study and phase III ROCKET-AF trial (N Engl J Med. 2011;365:883-91) were slightly different. 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 respective CHADS2 scores of 2.0 and 3.5. The incidence of major bleeding was also slightly higher in the ROCKET-AF, at 3.6% per year, which was similar to that seen with warfarin (3.4%; P = .58), the active comparator used.
Nevertheless, the findings of the XANTUS study, which were published online simultaneously with their presentation at the conference (Eur Heart J. Sep 1. doi: 10.1093/eurheartj/ehv466), highlight the “real-world” safety of rivaroxaban, Dr. Camm said.
Results from the separate PMSS (Post-Marketing Safety Surveillance) study reported in a poster at the meeting were similar. The PMSS study is being conducted in the United States and is an ongoing, retrospective, 5-year, observational study of more than 39,000 patients with nonvalvular atrial fibrillation. At 2 years follow-up, the incidence of major bleeding was 2.89% per year and the incidence of fatal bleeding was 0.1% per year (Eur Heart J. 2015;36:687.P4066).
“Real-world research is an essential complement to clinical trials and helps inform treatment decisions,” PMSS study investigator Dr. Frank Peacock said in a press release issued by Janssen. Dr. Peacock, who is professor of emergency medicine at Baylor College of Medicine in Houston, added, “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 U.S. Food and Drug Administration requirements on the long-term monitoring of medicines. There are also similar programs running in other world regions, such as XANTUS-EL and XANAP.
Other real-world data gleaned from electronic medical records (EMRs) comparing the potential bleeding risks of the factor Xa inhibitor apixaban (Eliquis) versus other available non–vitamin K antagonists (NOACs) including rivaroxaban and the direct thrombin inhibitor dabigatran (Pradaxa) were reported in several posters supported by Bristol-Myers Squibb and Pfizer and in an oral presentation given by Dr. Gregory Lip of the University of Birmingham, England.
Two of the posters reported data from retrospective analyses of different United States EMRs of 29,338 and 35, 757 patients, respectively, with nonvalvular atrial fibrillation newly started on a NOAC or warfarin in 2013 or 2014. Most were started on warfarin (43.3%/69.6%), followed by rivaroxaban (34.3%/17.9%), dabigatran (14.2%/6.8%), and apixaban (8.2%/5.7%).
Results of the first study (Eur Heart J. 2015;36:1085.P6217) showed that patients newly starting treatment with a NOAC had significantly lower rates of major bleeding than those starting treatment with warfarin, which was 4.6% per year versus 2.35% per year for apixiban, 3.38% per year for dabigatran, and 4.57% per year for rivaroxaban in the first study.
In the second study (Eur Heart J. 2015;36:1085.P6215) the respective adjusted hazard ratios for bleeding risk were 1.094, 0.747 and 0.679, comparing rivaroxaban, apixaban, and dabigatran against warfarin.
Other data gleaned from separate U.S. EMRs suggested that apixaban was associated with fewer bleeding-related hospital readmissions than either rivaroxaban or dabigatran in hospitalized patients with nonvalvular atrial fibrillation (Eur Heart J. 2015;36: 1085.P6211).
Dr. Lip presented 6-month follow-up data on more than 60,000 patients with nonvalvular atrial fibrillation who were treated with one of the three NOACs that was recorded in a U.S. medical claims database (Eur Heart J. 2015;36:339.1975). Most of the patients were treated with rivaroxaban (50.6%), with 34.8% treated with dabigatran and 14.6% 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.