Clinical Question

Is low-dose edoxaban (Savaysa) safe and effective for stroke prevention in older patients with atrial fibrillation?

Bottom Line

A lower dose of edoxaban is effective in decreasing stroke and systemic embolism in older patients with atrial fibrillation compared with placebo (number needed to treat = 23). Although the difference in major bleeding rates with edoxaban vs. placebo did not reach statistical significance, edoxaban use led to higher rates of gastrointestinal bleeding (number needed to harm = 83) and clinically significant nonmajor bleeding (number needed to harm = 18). This study was completed in Japan, and the mean body mass index of participants was 22 kg per m², which may not generalize to the population in the United States. (Level of Evidence = 2b)

Synopsis

Many older patients with atrial fibrillation may not be prescribed standard doses of anticoagulation for stroke prevention because of a perceived higher risk of bleeding. In this Japanese study, investigators enrolled patients 80 years and older with nonvalvular atrial fibrillation and a CHADS₂ (congestive heart failure; hypertension; age 75 years or older; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism [doubled]) score of 2 or more for whom standard doses of oral anticoagulants were considered inappropriate (e.g., those with a history of critical bleeding, severe renal impairment, low body weight, continuous nonsteroidal anti-inflammatory drug use, or antiplatelet drug use). A total of 984 patients were randomized to receive edoxaban, 15 mg daily (standard dose is 60 mg or 30 mg daily), or a matched placebo. The two groups had similar baseline characteristics: mean age of 86.6 years, mean body weight of 111.5 lb (50.6 kg), and a mean CHADS₂ score of 3. The annualized rate of stroke or systemic embolism was lower in the edoxaban group than in the placebo group (2.3% vs. 6.7%; hazard ratio [HR] = 0.34; 95% CI, 0.19 to 0.61; P < .001). The incidence of major bleeding was higher in the edoxaban group, although this difference did not reach significance (3.3% for edoxaban vs. 1.8% for placebo; P = .09). The edoxaban group had statistically significant higher rates of gastrointestinal bleeding (2.3% vs. 0.8%; HR = 2.85; 95% CI, 1.03 to 7.88) and clinically relevant nonmajor bleeding (14.5% vs. 8.9%; HR = 1.62; 95% CI, 1.14 to 2.30).

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)

Reference: Okumura K, Akao M, Yoshida T, et al.; ELDERCARE-AF Committees and Investigators. Low-dose edoxaban in very elderly patients with atrial fibrillation. N Engl J Med. 2020;383(18):1735–1745.