Impact of differences in body mass index, body surface area and lean body mass on clinical outcomes in patients with atrial fibrillation receiving edoxaban: 4-year follow-up data from ETNA-AF-Europe

Abstract Background In patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants, extremes in body weight and its anthropometric correlates (body mass index [BMI], body surface area [BSA] and lean body mass [LBM]) may affect drug exposure and the occurrence of thromboembolic or haemorrhagic events. Purpose To investigate the association of BMI, BSA and LBM with clinical outcomes according to sex in edoxaban-treated patients with AF using 4-year data from ETNA-AF-Europe (NCT02944019). Methods The prospective, observational ETNA-AF-Europe study followed patients with AF receiving edoxaban for up to 4 years. In this subanalysis, patients were categorised into tertiles (low, middle, and high) for BMI, BSA and LBM and stratified by sex. Baseline characteristics and rates of any thromboembolic and haemorrhagic events per 100 patient-years ([%]/100PY) are reported using 4-year follow-up data. Results Of 13,164 patients, 7461 were men and 5703 were women. Table 1 shows the ranges of BMI, BSA and LBM, defining the low, middle, and high tertiles, and their corresponding baseline characteristics. Irrespective of sex, patients in the low tertile for BMI, BSA and LBM were older and more likely to have renal impairment, history of stroke, and to receive appropriate edoxaban 30mg or non-appropriate edoxaban 60mg. Patients in the high tertile were more likely to have diabetes and hypertension. Overall, the rate (%)/100PY of any thromboembolic event was slightly lower (0.8 vs 1.1%), whereas the corresponding rate of any haemorrhagic event was slightly higher (1.9 vs 1.7%) in men vs women (Figure 1). For BMI, BSA and LBM in men, rates (%)/100PY of any thromboembolic event were similar among tertiles (low, middle, high; BMI, 0.9, 0.8 and 0.8%; BSA, 0.9, 0.8 and 0.8%; LBM, 0.9, 0.7 and 0.9%). For BMI, rates (%)/100PY of any haemorrhagic event were similar among tertiles in men (BMI, 1.9, 1.8 and 2.0%), but highest in the low tertile for BSA and LBM (BSA, 2.4, 1.8 and 1.5%; LBM, 2.4, 1.8 and 1.5%). In women, rates (%)/100PY of any thromboembolic event were similar for all tertiles of BMI but were highest in the low tertile for BSA and LBM (low, middle, high; BMI, 1.3, 1.1 and 1.1%; BSA, 1.4, 1.1 and 1.0%; LBM, 1.4, 1.2 and 0.9%; Figure 1). For BMI, BSA and LBM, rates (%)/100PY of any haemorrhagic event were highest in the low tertile in women (low, middle, high; BMI, 2.1, 1.6 and 1.6%; BSA, 2.2, 1.7 and 1.4%; LBM, 2.3, 1.5 and 1.5%). Conclusions At the 4-year follow-up in this real-life registry, low rates (%/100PY) of any thromboembolic event ([0.7–1.4%]) were observed regardless of patients' BMI, BSA, LBM, or sex. However, higher rates of any haemorrhagic events were observed in the low ([2.2–2.4%]) vs middle ([1.5–1.8%]) and high ([1.4–1.5%]) tertiles for BSA and LBM, suggesting that these variables, more than BMI, should be considered when analysing outcomes in patients with AF treated with edoxaban.Baseline characteristicsFigure 1