Low rates of stroke and bleeding with NOAC in AF patients at extremes of body weight
Introduction and methods
Underweight and overweight may be associated with increased thrombotic and hemorrhagic risks. Also, pharmacokinetics of anticoagulants may be altered in individuals at the extremes of body weight  and the effects of altered pharmacokinetics/pharmacodynamics of NOACs in these individuals are unknown [2,3]. The ISTH SSC (International Society of Thrombosis and Hemostasis Scientific and Standardisation Committee) suggested to avoid use of NOACs in obese patient (>120 kg or BMI >40 kg/m2), but clear guidance on use of NOACS in patients with underweight was not provided .
This subgroup analysis of ETNA-AF-Europe registry examined the clinical outcomes in patients treated with edoxaban across a range of body weight (≤60 kg [n=1310], >80-≤100 kg [n=4335], >100 kg [n=1446]) compared to the reference weight group (>60-≤80 kg, [n=5565]). Also, clinical outcomes were assessed across a range of BMI (<18.5 kg/m2, ≥25-<30 kg/m2, ≥30-<35 kg/m2, >35 kg/m2) compared to the normal BMI group (≥18-<25 kg/m2).
ETNA-AF-Europe is a multinational, multicenter, post-authorization, observational study in 10 European countries. This analysis reported on one-year outcomes of 13,092 AF patients treated with edoxaban. Annualized event rates (% per patient-year) were reported for safety and effectiveness outcomes. 62.7% Of patients in the lower weight group received recommended edoxaban 30 mg, suggesting that the remaining patients received a higher dose than recommended. A limited number of patients with higher weight received lower than recommended doses.
- Risk of stroke/SEE and ischemic stroke at 1 year was 0.82%/year and 0.56%/year in the total group, with no differences in risk among weight groups both in the unadjusted model and after adjustment for eGFR and CHA2DS2-VASc score.
- Rates of major bleeding and ICH were 1.05%/year and 0.24%/year in the overall population, with no difference is risk among weight groups after adjustment for eGFR and CHA2DS2-VASc score.
- Annualized event rates due to any cause deaths decreased with increasing weight, with an annualized event rate of 3.50%/year for death due to any cause in the overall population. After adjustment, risk of all-cause death was higher in the lower weight group (≤60 kg) and the group of >80-≤100 kg and >100 kg compared to the reference group (HR 1.41, 95%CI:1.08-1.84, HR 1.29, 95%CI: 1.01-1.65, HR 2.04, 95%CI: 1.35-3.10).
- Rates of CV-related deaths also decreased with increasing weight, with an annualized event rate of 1.63%/year in the overall population. After adjustment for eGFR and CHA2DS2-VASc score, risk of CV-related death was not different according to weight categories.
- When analyzing data according to BMI categories, risk of death and CV death was increased in underweight patients compared to patients with normal BMI. No differences in risk of death due to any cause and CV death were observed with higher than normal BMI.
This subanalysis of the ETNA-AF-Europe registry showed that risk of stroke and bleeding was low in patients with AF treated with edoxaban, with no significant differences in rates across weight categories. A higher risk of death due to any cause was observed in lower and higher weight categories compared to the reference group (U-curve association), which is in contrast with previous findings that described an “obesity paradox” for mortality.