Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation
Increasing age and atrial fibrillation are independent risk factors for stroke. In earlier trials, the mean or median age was 70 -73 years in patients with atrial fibrillation. It’s challenging to implement anticoagulative medicine in very elderly patients with atrial fibrillation due to the risk of bleeding.
The Japanese authors K. Okumura and colleagues (2020) conducted a phase 3 trial, entitled “Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation” published in “The New England Journal of Medicine”. Below is the summary of Phase III, multicenter, randomized, double-blind, placebo-controlled, event-driven trial.
Objective:
To find an effective anticoagulant regimen in high-risk, very elderly patients.
Method:
A total of 984 elderly patients, aged ≥80 years, with nonvalvular atrial fibrillation, were recruited. These elderlies were not considered to be appropriate candidates for oral anticoagulant therapy at doses approved for stroke prevention. Patients were randomly assigned to two groups in 1:1 ratio. 492 patients were assigned to a group receiving a daily dose of 15 mg of edoxaban. And 492 patients were assigned to the placebo group. 151 patients from the edoxaban receiving group and 150 patients from the placebo group discontinued from the trial due to various reasons.
The primary endpoint of the study was the composite of stroke or systemic embolism, and the primary safety endpoint was major bleeding defined according to the International Society on Thrombosis and Haemostasis.
Result:
Patients of the study had a mean age of 86.6±4.2 years with a mean lean bodyweight of 50.6±11.0 kg. Their mean creatinine clearance was 36.3±14.4 ml per minute and 40.9% of the patients were categorized as frail individuals. 15 vs 44 patients of edoxaban and placebo group, respectively, had a stroke or systemic embolism (hazard ratio, 0.34; 95% confidence interval [CI], 0.19 to 0.61; P<0.001 for superiority). Deaths due to any causes was 11.1% in the edoxaban group and 14.8% in the placebo group. The events of bleeding were 20 in the edoxaban group and 11 in the placebo group (hazard ratio, 1.87; 95% CI, 0.90 to 3.89; P = 0.09). The events of bleeding include intracranial hemorrhages and gastrointestinal bleeding.
Even though there were substantially more events of bleeding in the edoxaban group, edoxaban did not result in higher incidences of death.
Limitations:
The authors acknowledged that the trial had few limitations. Multiple patients withdrew either due to their high-risk background, adverse events, inability to continue to participate, or bleeding related issues. Secondly, the East Asian patients with atrial fibrillation had higher rates of overt bleeding of any kind in comparison to non-East Asian patients. Thus, the results of this study may not apply to non-East Asian populations.