Once-daily edoxaban was found to be more effective than placebo for the prevention of stroke and systemic embolism without increasing the risk for major bleeding in elderly patients with nonvalvular atrial fibrillation (AF), according to a study published in the New England Journal of Medicine.
In this phase 3, multicenter study, 984 elderly Japanese patients (mean age, 86.6±4.2 years) with nonvalvular AF were randomly assigned to receive once-daily 15-mg edoxaban or placebo (n=492 in each group). Participants had a CHADS2 score ≥2 (mean, 3.1±1.1), indicative of an elevated risk for stroke. None of the patients were considered to be appropriate candidates to receive standard doses of oral anticoagulant therapies for the prevention of stroke.
The study’s primary efficacy endpoint was a composite of stroke or systemic embolism, and the primary safety endpoint was major bleeding.
The annualized rates of stroke or systemic embolism in the intention-to-treat population were 2.3% and 6.7% in the edoxaban and placebo groups, respectively (hazard ratio [HR], 0.34; 95% CI, 0.19-0.61; P <.001). The annualized rate of major bleeding was comparable in the edoxaban and placebo groups (3.3% and 1.8%, respectively; HR, 1.87; 95% CI, 0.90-3.89; P =.09).
A greater percentage of gastrointestinal bleeding events occurred in the edoxaban vs placebo group (2.3% vs 0.8% per patient-years, respectively; HR, 2.85; 95% CI, 1.03-7.88). No between-group difference was observed for death from any cause (edoxaban, 9.9%; placebo, 10.2%; HR, 0.97; 95% CI, 0.69-1.36).
Study limitations include a high number of patients who discontinued the trial (n=303) as well as the sole inclusion of Japanese participants.
“Clinical guidelines for the prevention of stroke in patients with atrial fibrillation recommend the use of direct oral anticoagulants, including in elderly patients. However, many physicians are reluctant to prescribe direct oral anticoagulants to very elderly patients because of perceived risk factors for bleeding,” noted the study authors. “Considering the aging of the population, evidence to support a beneficial anticoagulation regimen in high-risk, very elderly patients is necessary.”
Disclosure: This clinical trial was supported by Daiichi Sankyo. Please see the original reference for a full list of authors’ disclosures.
Okumura K, Akao M, Yoshida T, et al. Low-dose edoxaban in very elderly patients with atrial fibrillation. Published online August 30, 2020. N Engl J Med. doi:10.1056/NEJMoa2012883