Rivaroxaban noninferior to warfarin for stroke, embolism in atrial fibrillation

Rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism in patients with atrial fibrillation, a study found.

A randomized, double-blind, double-dummy, event-driven trial assigned 14,264 patients from 1,178 sites in 45 countries, with nonvalvular atrial fibrillation documented by electrocardiography and at moderate-to-high risk for stroke, to receive either rivaroxaban (20 mg daily or 15 mg daily in patients with creatinine clearance of 30 to 49 mL/min) or dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0). The authors reported funding from Johnson & Johnson and Bayer. Results appeared in the Aug. 10 New England Journal of Medicine.

The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of ischemic or hemorrhagic stroke or systemic embolism. In that analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% CI, 0.66 to 0.96; P<0.001 for noninferiority).

In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority).

There were no significant differences in rates of major and clinically relevant bleeding. Bleeding occurred in 1,475 patients in the rivaroxaban group (14.9% per year) and in 1,449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44). Intracranial hemorrhage rates were significantly lower (hazard ratio, 0.67; 95% CI, 0.47 to 0.93; P=0.02) in the rivaroxaban group, as were rates of fatal bleeding (0.2% vs. 0.5%; P=0.003).

Editorialists wrote, “For the management of atrial fibrillation, oral alternatives to warfarin have arrived. Their simplicity of use is attractive, and they appear to have an efficacy similar to that of warfarin, with the proviso that comparisons seem to depend on how easily the patient can be treated with warfarin.” However, the editorialists continued, “An important concern that these clinical trials do not address is the absence of antidotes to rapidly reverse the anticoagulant effects of either rivaroxaban or dabigatran in the case of life-threatening hemorrhage or surgery.”