Introduction: Factor Xa activates protease-activated receptors and participates in tissue fibrosis. In addition, atrial fibrotic remodeling plays a pivotal role in the development of atrial fibrillation (AF).
Hypothesis: Direct factor Xa inhibitors may exhibit beneficial effects on these pathological conditions. We tested the inhibitory effect of edoxaban on AF promotion in a canine congestive heart failure (CHF) model induced by rapid ventricular pacing and compared with that of warfarin.
Methods: Eighteen beagles were allocated to 4 groups; (1) sham surgery control (CTL), n=6; (2) CHF + placebo (CHF-P), n=4; (3) CHF + edoxaban (CHF-E), n=4; (4) CHF + warfarin (CHF-W), n=4. Dogs were implanted ventricular pacemakers on day 0. Administration of placebo (in CTL and CHF-P), edoxaban (2 mg/kg, CHF-E), or warfarin (0.2-0.3 mg/kg, adjusted to PT-INR 2.0-3.0, CHF-W) was started on day 3 and rapid ventricular pacing (240 bpm, 2 weeks) on day 7, both continued until day 21 when electrophysiological and echocardiographic studies performed.
Results: CHF-P, CHF-E, and CHF-W dogs showed increased left ventricular (LV) dimensions, decreased LV ejection fraction, larger left atrial (LA) area, lower LA fractional area change, and longer atrial effective refractory period compared with CTL dogs. AF duration prolonged in CHF-P (148.5±69.6 s, p<0.05) vs. CTL (3.7±4.9 s). Edoxaban suppressed prolongation of AF (4.9±3.0 s in CHF-E, p=ns vs. CTL) while warfarin did not (233.7±131.2 s in CHF-W, p<0.05 vs. CTL). AF Inducibility was not different between 4 groups.
Conclusions: Edoxaban, but not warfarin, suppressed prolongation of AF in a canine CHF model induced by rapid ventricular pacing, suggesting anti-atrial remodeling effect of edoxaban in this model.