Atrial Fibrillation Symptom Risks Reduced by Rivaroxaban

Jeff S. Healey, MD, MSc

A prospective, real-world analysis of more than 11,000 patients across the globe has found that patients with atrial fibrillation (AF) experience lessened rates of bleeding, stroke, and treatment discontinuation when treated with rivaroxaban.

In a pre-planned pool analysis of the Xarelto for Prevention of Stroke in Patients With AF in Western Europe, Canada, and Isreal (XANTUS) , Asia-Pacific( XANAP), and Latin America, Middle East, Eastern Europe, and Africa (XANTUS-EL), researchers from a Bayer-funded global program observed consistently improved rates of adverse events (AEs) in adult AF patients given their country’s regulated dosage rate of rivaroxaban.

The label-recommended dose in all participating countries except Taiwan were 20 mg once-daily in patients with creatinine clearance (CrCl) of at least 50 ml/min. In Taiwan, the dosage can be adjusted to 15 mg rivaroxaban.

Primary outcomes included major bleeding events, all-cause death, and any other AEs or serious AEs (SAEs). Researchers also sought outcomes in symptomatic thromboembolic events, nonmajor bleeding, treatment satisfaction and persistence, and for any reasons why treatment was interrupted.

AF, a condition estimated to affect almost 34 million patients worldwide, is associated with major disease burden, predominately in the form of cardiovascular comorbidities. As a direct oral anti-coagulant (DOAC), rivaroxaban has been a proven inhibitor of ischemic stroke risks in patients with AF.

After clinical comparisons, its fellow DOAC drug class members—apixaban, dabigatran, and edoxaban—have become considered better therapies for patients with AF than standard vitamin K antagonists (VKA), researchers noted.

“On the basis of the results of large phase III trials that demonstrated the favorable benefit—risk profile of DOACs over VKAs, various guide- lines recommend DOACs as an alternative, or in preference to, VKAs,” researchers wrote. “DOACs are increasingly used for stroke prevention in patients with AF.”

Among the observed 11,121 patients, mean age was 70.5 years, with 57.1% being male. At baseline, common comorbidities included hypertension (76.2%), diabetes (22.3%), prior stroke (21.3%) and congestive heart failure (21.2%).

A majority of patients from each region were administered once-daily 20 mg rivaroxaban for 12 months. Researchers noted 8540 (76.8%) of the patients participating in the study were observed for the full 12 months, with premature discontinuation being reported in 2556 (23.1%) patients.

Among those who ended prematurely, 794 (7.1%) had decided to no longer continue, and 724 (6.5%) were due to AE.

Event rates per 100 patient-years were 1.7 for major bleeding (95% CI; 1.5-2.0), 1.9 for all-cause death (95% CI; 1.6-2.2), and 1.0 for stroke or systemic embolism (95% CI; 0.8-1.2).

More than 96% of patients administered rivaroxaban did not experience any of the marked AEs for observation, researchers noted. As having consistent improvements across patient regions in the largest prospective, observational analysis of a single DOAC for the prevention of stroke in patients with AF, the study was considered a success.

In an essay accompanying the study, Jeff S. Healey, MD, MSc, from the Population Health Research Institute at McMaster University, noted that, though the data is not population based, it is a proper representation of what a clinician would expect in prescribing a DOAC under the regional guidelines provided, as well as a “testament to the successful introduction of DOACs into the clinical practice.”

“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,” Healey wrote.

The proven, real-world data has enough merit to give the Xarelto-based trials definite superlative.

“The clinical trials of anti-coagulation for stroke prevention in AF are among the most successful in all of medicine,” Healey wrote. “Now, it appears that the translation of their results into clinical practice has achieved a similar status.”

The study, "Global Prospective Safety Analysis of Rivaroxaban," was published online in JACC this week.