Impact of Weight on Clinical Outcomes of Edoxaban Therapy in Atrial Fibrillation Patients Included in the ETNA-AF-Europe Registry

Abstract

Background: Extremes of body weight may alter exposure to non-vitamin K antagonist oral anticoagulants and thereby impact clinical outcomes. This ETNA-AF-Europe sub-analysis assessed 1-year outcomes in routine care patients with atrial fibrillation across a range of body weight groups treated with edoxaban. Methods: ETNA-AF-Europe is a multinational, multicentre, observational study conducted in 825 sites in 10 European countries. Overall, 1310, 5565, 4346 and 1446 enrolled patients were categorised into ≤60 kg, >60–≤80 kg (reference weight group), >80–≤100 kg and >100 kg groups. Results: Patients weighing ≤60 kg were older, more frail and had a higher CHA2DS2-VASc score vs. the other weight groups. The rates of stroke/systemic embolism, major bleeding and ICH were low at 1 year (0.82, 1.05 and 0.24%/year), with no significant differences among weight groups. The annualised event rates of all-cause death were 3.50%/year in the overall population. After adjustment for eGFR and CHA2DS2-VASc score, the risk of all-cause death was significantly higher in extreme weight groups vs. the reference group. Conclusions: Low rates of stroke and bleeding were reported with edoxaban, independent of weight. The risk of all-cause death was higher in extremes of weight vs. the reference group after adjustment for important risk modifiers, thus no obesity paradox was observed.

Risks and benefits of oral anticoagulants for stroke prophylaxis in atrial fibrillation according to body mass index: Nationwide cohort study of primary care records in England

“…Novel RCT evidence to address the use of DOACs compared with warfarin for stroke prophylaxis in AF patients with very low or very high BMI is unlikely given that many of the DOACs are nearing patent end. 20 Previous population-based studies have either included only a very small number of underweight patients, 21 only provided data for one DOAC, 22 or included venous thromboembolism as an indication for prescription. 21 …”

Pharmacokinetics and Dosing Regimens of Direct Oral Anticoagulants in Morbidly Obese Patients: An Updated Literature Review

“…In the post hoc analysis of the ETNA-AF-Europe trial evaluated 1-year outcomes in AF patients treated with edoxaban across a range of body weight groups, edoxaban seemed associated with a very low occurrence of stroke and bleeding, and there were no differences in the risks of stroke/SE (HR 1.14, 95% CI 0.48-2.71), major bleeding (HR 0.67, 95% CI 0.27-1.66), major or CRNM bleeding (HR 0.98, 95% CI 0.57-1.69), and intracranial hemorrhage (HR 0.93, 95% CI 0.17-5.10) among body weight groups after adjustment for eGFR and CHA2DS2-VASc score. 45 However, the morbid obesity cutoff point was >100 kg, which may not be extrapolated to patients with BMI >40 kg/m 2 or weight >120 kg.…”

Risks and Benefits of Oral Anticoagulants for Stroke Prophylaxis in Atrial Fibrillation According to Body Mass Index: Nationwide Cohort Study of Primary Care Records in England

“…After application of inclusion and exclusion criteria 29,135 patients formed the analytical cohort before matching (Supplementary Figure S2). Of those patients, 22 Fig. 1 shows that overall 78.3% of patients were prescribed warfarin, but initial prescription of warfarin declined during the study period from 95.7% in 2012 to 5.9% in 2018 with a concurrent increase in prescription of DOACs.…”

“…Novel RCT evidence to address the use of DOACs compared with warfarin for stroke prophylaxis in AF patients with very low or very high BMI is unlikely given that many of the DOACs are nearing patent end. 20 Previous population-based studies have either included only a very small number of underweight patients, 21 only provided data for one DOAC, 22 or included venous thromboembolism as an indication for prescription. 21 Observational studies conducted in the United States of America have found a similar or lower risk for stroke/ systemic embolism and major bleeding for apixaban, rivaroxaban and dabigatran compared with warfarin in obese cohorts.…”