AIMS: Patients with atrial fibrillation (AF) are at increased risk of stroke. 
Betrixaban is a novel oral factor Xa inhibitor administered once daily, mostly 
excreted unchanged in the bile and with low (17%) renal excretion.
METHODS AND RESULTS: Patients with AF and more than one risk factor for stroke 
were randomized to one of three blinded doses of betrixaban (40, 60, or 80 mg 
once daily) or unblinded warfarin, adjusted to an international normalized ratio 
of 2.0-3.0. The primary outcome was major or clinically relevant non-major 
bleeding. The mean follow-up was 147 days. Among 508 patients randomized, the 
mean CHADS2 score was 2.2; 87% of patients had previously received vitamin K 
antagonist therapy. The time in therapeutic range on warfarin was 63.4%. There 
were one, five, five, and seven patients with a primary outcome on betrixaban 
40, 60, 80 mg daily, or warfarin, respectively. The rate of the primary outcome 
was lowest on betrixaban 40 mg (hazard ratio compared with warfarin = 0.14, 
exact stratified log-rank P-value 0.04, unadjusted for multiple testing). Rates 
of the primary outcome with betrixaban 60 or 80 mg were more similar to those of 
wafarin. Two ischaemic strokes occurred, one each on betrixaban 60 and 80 mg 
daily. There were two vascular deaths, one each on betrixaban 40 mg and 
warfarin. Betrixaban was associated with higher rates of diarrhoea than 
warfarin.
CONCLUSION: Betrixaban was well tolerated and had similar or lower rates of 
bleeding compared with well-controlled warfarin in patients with AF at risk for 
stroke.