A large, multicenter, randomized study of 14, 264 patients at risk for stroke with nonvalvular atrial fibrillation (AF) found the factor Xa inhibitor rivaroxaban to be noninferior to warfarin for preventing stroke or systemic embolism.
The ROCKET AF investigators, who reported the results online August 10 in The New England Journal of Medicine, detected no significant difference between rivaroxaban and warfarin in the rates of major or nonmajor clinically relevant bleeding.
Investigators at 1178 study sites in 45 countries randomly assigned the patients to receive either fixed-dose rivaroxaban at 20 mg daily or adjusted-dose warfarin to a target of INR 2.0 – 3.0. Patients with a creatinine clearance of 30-49 mL/minute received a rivaroxaban dose of 15 mg daily.
Patients in both arms of the intent-to-treat population were a median age of 73 years and about 40% were women. The patients had considerable rates of coexisting conditions, including 90.5% with hypertension, 62.5% with heart failure, and 54.8% who had had a previous stroke, embolism, or transient ischemic attack.
After a median treatment duration of 590 days, the primary efficacy analysis showed188 patients (1.7% per year) in the rivaroxaban group had a stroke or systemic embolism, compared with 241 patients (2.2% per year) in the warfarin group (P<0.001 for noninferiority).
Rates of major bleeding were similar in the 2 groups—3.6% with rivaroxaban and 3.4% with warfarin (P=0.58). Major and clinically relevant nonmajor bleeding occurred in 1475 (14.9%) rivaroxaban-treated patients and 1449 (14.5%) warfarin-treated patients (P=0.44). Intracranial and fatal bleeding occurred less often in the rivaroxaban group.
The investigators noted that the warfarin-treated patients were in therapeutic range a mean of 55% of the time. However, the efficacy of rivaroxaban was as favorable in those centers with the best INR control as it was in those with inferior control.
Lead author Manesh R. Patel, MD, of Duke University School of Medicine in North Carolina, said, “Warfarin has been a standard treatment for decades, but requires a rigorous monitoring schedule to ensure therapeutic dosing levels, and is subject to the potential of food and drug interactions that present treatment obstacles for patients and doctors alike.”
He indicated that the result of the trial “have convincingly shown rivaroxaban to be an alternative to warfarin in treating patients with atrial fibrillation, and importantly, with no increase in bleeding.”
The study was funded by Johnson & Johnson and Bayer.
ROCKET AF stands for Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in Atrial Fibrillation.
