Large Review of Xarelto in Nonvalvular Atrial Fibrillation Shows Low Rate of Major Bleeding

January 15, 2015—Janssen Pharmaceuticals, Inc. announced that a new postmarketing study evaluating the safety of once-daily Xarelto (rivaroxaban) shows that in patients with nonvalvular atrial fibrillation (NVAF), the rates and patterns of major bleeding in routine clinical practice are generally consistent with those observed in phase 3 clinical trials used to approve the medicine for this indication. These 15-month results represent initial findings from an ongoing, 5-year, observational study of patients using Xarelto daily over the course of their lives. Janssen and Bayer HealthCare together are developing rivaroxaban, noted the company. 

Sally Tamayo, MD, et al published the findings online ahead of print in Clinical Cardiology. The study investigators also concluded that fatal bleeds were rare.

Investigators analyzed data from January 1, 2013 to March 31, 2014, using US Department of Defense integrated electronic health care records, via a collaboration with Health ResearchTx LLC, to evaluate major bleeding rates in NVAF patients treated with Xarelto in the real-world clinical setting.

Of the 27,467 patients receiving Xarelto, an incidence of major bleeding was observed at 2.86 per 100 person-years, which was generally consistent with rates reported in the ROCKET-AF clinical trial. Additionally, patients who experienced major bleeding were older (with a mean age of 78 years) and fatal outcomes were rare.

In the company’s press release, investigator W. Frank Peacock, MD, commenting, “These findings reaffirm the safety profile of Xarelto. We anticipate future findings from this 5-year observational study will continue to provide real-world information about the use of Xarelto in routine clinical practice.” Dr. Peacock is Associate Chair and Research Director, Emergency Medicine at Baylor College of Medicine in Houston, Texas.

A Baylor College of Medicine press release noted that the study showed that less than 2% of patients experienced major bleeding events, with the majority of those being gastrointestinal and not the more serious intracranial type. Out of those who did experience major bleeding, less than 3% ended in death. With past treatments, such as warfarin, much higher numbers of patients would have experienced intracranial bleeding with a higher chance of dying.

In the Baylor announcement, Dr. Peacock commented, “NVAF can have severe outcomes, and the limited treatments we had contain their own set of side effects that can also be deadly. We were basically trading a probable outcome of stroke or death for a less certain outcome of death due to internal bleeding. The newer drugs we are using to treat this disorder have been shown to be safer, but still have similar side effects albeit at lower rates, so we need to keep evaluating to find the most effective use.”

Dr. Peacock stated, “Overall, there was a low rate of bleeding events. The majority of bleeding events were gastrointestinal, which is less deadly than intracranial bleeding, therefore the mortality rate was low.” Dr. Peacock added that with past drugs there were also lifestyle restrictions that are not needed when taking rivaroxaban. He stated, “Patients couldn’t eat certain foods, such as spinach. While these restrictions might not seem dramatic, making sure our patients have a good quality of life is very important to overall well being and health.”

Dr. Peacock advised that these results were consistent with past studies but continued review of patient outcomes helps doctors weigh the benefits of certain types of treatments, learn who is most at risk for side effects, and allows them to educate the patient on all options.