OBJECTIVES: This study sought to report additional safety results from the 
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).
BACKGROUND: The ROCKET AF trial demonstrated similar risks of stroke/systemic 
embolism and major/nonmajor clinically relevant bleeding (principal safety 
endpoint) with rivaroxaban and warfarin.
METHODS: The risk of the principal safety and component bleeding endpoints with 
rivaroxaban versus warfarin were compared, and factors associated with major 
bleeding were examined in a multivariable model.
RESULTS: The principal safety endpoint was similar in the rivaroxaban and 
warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% 
confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but 
there were no differences between treatments in each age category (<65, 65 to 
74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), 
patients with a major bleed (n = 781) were more likely to be older, 
current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, 
and a lower calculated creatinine clearance and less likely to be female or have 
a prior stroke/transient ischemic attack. Increasing age, baseline diastolic 
blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease 
or GI bleeding, prior acetylsalicylic acid use, and anemia were independently 
associated with major bleeding risk; female sex and DBP <90 mm Hg were 
associated with a decreased risk.
CONCLUSIONS: Rivaroxaban and warfarin had similar risk for major/nonmajor 
clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior 
acetylsalicylic acid use, and anemia were associated with the risk of major 
bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the 
Prevention of Stroke and Non-Central Nervous System Systemic Embolism in 
Patients With Non-Valvular Atrial Fibrillation: NCT00403767).