Betrixaban 40 mg daily was associated with a lower rate of major or clinically relevant non-major bleeding compared with warfarin (HR 0.14) in patients with atrial fibrillation.
RCT (n=508)
Open-label for drug, double-blind for dose
1:1:1:1 allocation
Yes
Does betrixaban reduce major or clinically relevant non-major bleeding compared to warfarin in patients with atrial fibrillation?
Betrixaban at doses of 40-80 mg daily was well tolerated and associated with similar or lower rates of bleeding compared to well-controlled warfarin in patients with atrial fibrillation.
Effect estimate: HR 0.14 (95% CI 0.017-1.135)
Absolute Event Rate: 1% vs 7%
p-value: p=0.04
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.
Connolly et al. (2013) conducted an RCT in Atrial fibrillation (n=508). Betrixaban vs. Warfarin (target INR 2.0-3.0) was evaluated on Time to occurrence of major or clinically relevant non-major (CRNM) bleeding (HR 0.14, 95% CI 0.017-1.135, p=0.04). Betrixaban 40 mg daily was associated with a lower rate of major or clinically relevant non-major bleeding compared with warfarin (HR 0.14) in patients with atrial fibrillation.