Low-dose edoxaban beneficial in older AF patients with extremely low body weight

In the treatment of older patients with nonvalvular atrial fibrillation (AF) who are considered ineligible for oral anticoagulants at the recommended therapeutic strength or the approved doses, the use of low-dose edoxaban helps reduce the risk of stroke or systemic embolism regardless of body weight, although this benefit comes with a slightly higher major bleeding events, according to the subgroup analysis of the phase III ELDERCARE‐AF trial.

In a cohort of 984 Japanese patients, the primary outcome of stroke or systemic embolism occurred less frequently with edoxaban 15 mg than with placebo both in the subgroups of patients with body weight of ≤45 kg (3.4 percent vs 9.0 percent per patient-year) and those with body weight of >45 kg (1.6 percent vs 5.4 percent per patient‐year). [J Am Heart Assoc 2024;doi:10.1161/JAHA.123.031506]

Compared with placebo, low-dose edoxaban was associated with a more than 60-percent reduction in the risk of stroke or systemic embolism in both weight subgroups (≤45 kg: hazard ratio [HR], 0.36, 95 percent confidence interval [CI], 0.16–0.80; >45 kg: HR, 0.31, 95 percent CI, 0.13–0.73), with no significant interaction between treatment and body weight (p=0.82).

The most common major bleeding event was gastrointestinal bleeding in the edoxaban and placebo groups regardless of body weight. In the ≤45‐kg subgroup, for instance, the incidence rate of gastrointestinal bleeding was 2.8 percent and 0.9 percent per patient‐year in the respective treatment groups. None of the patients in this subgroup had intracranial haemorrhage.

Exploratory analysis showed no significant differences in the net clinical outcome and all‐cause death between the edoxaban and placebo groups across all weight subgroups (>57.9 kg, >49.0 to ≤57.9 kg, >42.0 to ≤49.0 kg, and ≤42.0 kg).

“The present study suggests that edoxaban 15 mg could be a treatment option even in very underweight, elderly patients with AF, although the incidence of major bleeding with treatment was notable,” the investigators said.

“However, caution should be exercised in this setting because major bleeding tended to increase in the underweight group. In fact, six of nine major bleeding events in the ≤45-kg subgroup were gastrointestinal bleeds, which is consistent with previous reports that direct oral anticoagulants increase gastrointestinal bleeding,” they pointed out. [N Engl J Med 2009;361:1139-1151; N Engl J Med 2011;365:883-891; N Engl J Med 2011;365:981-992; N Engl J Med 2013;369:2093-2104]

ELDERCARE‐AF included 984 patients who had been randomly assigned to either the edoxaban group (n=492) or the placebo group (n=492). Of these, 38.0 percent had body weight of ≤45 kg group and 62.0 percent had body weight of >45 kg. Most patients (53.2 percent) in the ≤45‐kg subgroup weighed between 40 and 45 kg.

The mean body weight was 39.8 kg in the ≤45‐kg subgroup and 57.2 kg in the >45‐kg subgroup, and the mean age was 87.8 and 85.8 years in the respective subgroups. The body mass index, creatinine clearance, prevalence of comorbidities (coronary artery disease, dyslipidemia, and diabetes), HAS‐BLED score, continuous use of nonsteroidal anti‐inflammatory drugs, and use of an antiplatelet drug were lower in the ≤45‐kg subgroup.