Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation

BACKGROUND: Providing appropriate oral anticoagulant treatment for stroke prevention in very elderly patients with atrial fibrillation poses a challenge due to bleeding concerns.

METHODS: A phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven trial was conducted to compare a once-daily 15-mg dose of edoxaban with placebo. The study population comprised elderly Japanese patients (80 years of age or older) with nonvalvular atrial fibrillation who were deemed unsuitable candidates for standard-dose oral anticoagulant therapy for stroke prevention. The primary efficacy end point was a composite of stroke or systemic embolism, while the primary safety end point was major bleeding, as defined by the International Society on Thrombosis and Haemostasis.

RESULTS: A total of 984 patients were randomized in a 1:1 ratio to receive either 15 mg of edoxaban daily (492 patients) or placebo (492 patients). Of these, 681 patients completed the trial, and 303 discontinued (due to withdrawal, death, or other reasons). The median follow-up period was 2.1 years (interquartile range, 1.0 to 3.0). The primary efficacy end point occurred in 21 patients (1.4% per patient-year) in the edoxaban group, compared to 71 patients (5.6% per patient-year) in the placebo group (hazard ratio, 0.23; 95% confidence interval [CI], 0.14 to 0.38; P<0.001). The primary safety end point was observed in 15 patients (1.1% per patient-year) in the edoxaban group and 16 patients (1.2% per patient-year) in the placebo group (hazard ratio, 0.90; 95% CI, 0.46 to 1.74; P=0.76). There were 23 deaths in the edoxaban group versus 47 in the placebo group (hazard ratio, 0.49; 95% CI, 0.29 to 0.83).

CONCLUSIONS: Among very elderly Japanese patients with atrial fibrillation who were not suitable for standard-dose oral anticoagulant therapy, treatment with low-dose edoxaban significantly reduced the incidence of stroke or systemic embolism without a significant increase in major bleeding events

BACKGROUND: Providing appropriate oral anticoagulant treatment for stroke prevention in very elderly patients with atrial fibrillation poses a challenge due to bleeding concerns.

METHODS: A phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven trial was conducted to compare a once-daily 15-mg dose of edoxaban with placebo. The study population comprised elderly Japanese patients (80 years of age or older) with nonvalvular atrial fibrillation who were deemed unsuitable candidates for standard-dose oral anticoagulant therapy for stroke prevention. The primary efficacy end point was a composite of stroke or systemic embolism, while the primary safety end point was major bleeding, as defined by the International Society on Thrombosis and Haemostasis.

RESULTS: A total of 984 patients were randomized in a 1:1 ratio to receive either 15 mg of edoxaban daily (492 patients) or placebo (492 patients). Of these, 681 patients completed the trial, and 303 discontinued (due to withdrawal, death, or other reasons). The median follow-up period was 2.1 years (interquartile range, 1.0 to 3.0). The primary efficacy end point occurred in 21 patients (1.4% per patient-year) in the edoxaban group, compared to 71 patients (5.6% per patient-year) in the placebo group (hazard ratio, 0.23; 95% confidence interval [CI], 0.14 to 0.38; P<0.001). The primary safety end point was observed in 15 patients (1.1% per patient-year) in the edoxaban group and 16 patients (1.2% per patient-year) in the placebo group (hazard ratio, 0.90; 95% CI, 0.46 to 1.74; P=0.76). There were 23 deaths in the edoxaban group versus 47 in the placebo group (hazard ratio, 0.49; 95% CI, 0.29 to 0.83).

CONCLUSIONS: Among very elderly Japanese patients with atrial fibrillation who were not suitable for standard-dose oral anticoagulant therapy, treatment with low-dose edoxaban significantly reduced the incidence of stroke or systemic embolism without a significant increase in major bleeding events