Abstract Body (Do not enter title and authors here): Background: The incidence of embolic events has been reported to be high early after bioprosthetic valve (BPV) replacement, thus the current guidelines recommend anticoagulant therapy with vitamin K antagonists for 3 to 6 months after operation. However, warfarin has a narrow therapeutic range and interacts with other drugs and food.
Hypothesis and Purpose: Our hypothesis is that the efficacy and safety of edoxaban are comparable to warfarin in patients early after BPV replacement.
Study Design: An investigator-initiated, phase 3, randomized, open-label, multicenter study (jRCT2051210209).
Population Studied: Patients aged 18 to 85 years undergoing BPV replacement at the aortic and/or mitral position.
Intervention: Edoxaban versus warfarin
Methods: Patients were randomized 1:1 to receive either edoxaban (60 or 30mg once daily adjusted by renal function, body weight, and concomitant use of P-glycoprotein inhibitors) or warfarin (dose adjusted under monitoring PT-INR). Administration of edoxaban or warfarin was continued for 12 weeks after surgery.
Sample Size: The sample size was set at 450 to account for 10% dropout.
Power Calculations: The event incidence rates in the edoxaban and warfarin groups were assumed to be 1-3% each. A difference of no more than 2% in the event incidence rate between the edoxaban group and warfarin group was considered a clinically acceptable margin. The probability that the point estimate of the difference in event incidence rates would fall within this threshold was calculated to be approximately 90%.
Primary End Points: Stroke or systemic embolism at 12 weeks after surgery.
Secondary End Points: Major bleeding, intracardiac thrombus, and a composite of stroke, systemic embolism, or major bleeding.
Outcomes: Of 410 enrolled patients, 389 were included in the final analysis (73±6 years, 56.8% male, 79.4% sinus rhythm, edoxaban group: n=195, warfarin group: n=194). The primary outcome occurred in 0.5% (n=1) in the edoxaban group, whereas in 1.5% (n=3) in the warfarin group (risk difference, −1.03, 95%CI, −4.34 to 1.95). The incidence of major bleeding was numerically higher in the edoxaban group (4.1% vs 1.0%, risk difference, 3.07; 95%CI, −0.67 to 7.27), but no fatal bleeding or intracranial hemorrhage was observed, whereas one fatal intracranial hemorrhage occurred in the warfarin group. Our results suggest that edoxaban is a potential alternative anticoagulant therapy early after BPV replacement, including patients with sinus rhythm.