ROCKET AF Study Compares Rivaroxaban and Warfarin in Atrial Fibrillation Patients

November 15, 2010—Trial results presented at the American Heart Association's (AHA) Scientific Sessions 2010 in Chicago suggest that rivaroxaban (Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, NJ; and Bayer HealthCare AG, Leverkusen, Germany) is as effective as the standard medication in preventing stroke and blood clots and does not increase bleeding risk among patients with atrial fibrillation. ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) is a randomized, double-blind clinical trial funded by Johnson & Johnson and Bayer HealthCare.

According to the AHA, the ROCKET AF investigators compared rivaroxaban with warfarin in 14,264 patients with atrial fibrillation that was not related to heart valve disease at more than 1,100 hospitals in 45 countries. The median age was 73 years, and 43.5% of patients were 75 years or older. In addition, 40% of patients were women and 83% were white. More than half (55%) of the patients had a previous stroke or a transient ischemic attack. The median time that patients spent in the therapeutic range with warfarin during the course of the trial was 57.8%. Patients spent on average 11.9% of time above the therapeutic range, and they were below this range 19.7% of the time.

The investigators randomized participants to receive either 20 mg of rivaroxaban daily or an appropriately adjusted dose of warfarin. The study was conducted from December 2006 to May 2010, and average treatment lasted 19 months.

“Warfarin is an effective drug to prevent stroke and emboli in the condition of atrial fibrillation, but it has to be monitored and many people are unhappy taking it,” stated Keith A.A. Fox, MD, cochair of the study. “Patients and clinicians have been looking for an alternative for a long time, and the investigation of oral factor Xa inhibitors provided a good opportunity to see if a different class of drugs could be effective.”

In the primary analysis, measuring the reaction of patients while they were taking the study drug, patients taking rivaroxaban compared with warfarin had fewer strokes and emboli to other parts of the body. In the rivaroxaban group, there were 1.71 events per 100 patient years (188 patients); in the warfarin group, there were 2.16 (241 patients) (P < .001 for noninferiority; P = .018 for superiority). Major bleeding complications were comparable in both treatment groups, occurring at a rate of 3.6 per 100 patient years (395 patients) with rivaroxaban and 3.45 per 100 patient years (386 patients) with warfarin (P = .576).

The full intention-to-treat analysis, which counts all events from the time of randomization until study completion, regardless of whether participants were taking medication, found fewer strokes and blood clots occurred in participants assigned to rivaroxaban (269 patients) versus warfarin (306 patients). However, this difference fell short of statistical significance for declaring rivaroxaban superior to warfarin (P = .177). Bleeding inside the skull cavity and/or brain tissue occurred in 55 patients on rivaroxaban and 84 patients on warfarin (P = .019).

“The main implication is that we have an alternative to warfarin,” commented Robert M. Califf, MD, coprincipal investigator of the study. “Equally important, there was no increase in bleeding, so we have a drug you can take once a day, without monitoring, that is at least as good as warfarin and carries no additional risk.”

According to the AHA, rivaroxaban is one of several new drugs now in clinical trials that seek to replace warfarin, which for more than 50 years has been the primary anticlotting medication on the market. Investigators have long sought a substitute for warfarin, which requires frequent monitoring because it can interact with other medications and certain foods to cause potentially excessive bleeding or lack of adequate blood thinning. Both rivaroxaban and warfarin prevent blood clots by blocking the action of vitamin-K-dependent protein clotting factors. Rivaroxaban targets the specific clotting factor Xa (ie, 10a).