Recommended and non-recommended edoxaban dosing in patients with atrial fibrillation (AF): one-year clinical events from the Global ETNA-AF non-interventional study (NIS)

Abstract Background In AF patients on direct oral anticoagulants (DOAC), safety and effectiveness vary with dose. This might impact treatment decisions. Purpose To investigate the effects of dosing of the DOAC edoxaban in AF patients on safety and effectiveness during 1-year observation in a real-world setting. Methods The Global ETNA-AF NIS included 26,823 patients. Baseline data by edoxaban dosing (60mg/30mg) and their influences on the safety (major bleeding [MB], clinically relevant non-major bleeding [CRNMB]), and effectiveness (stroke, systemic embolism, myocardial infarction [MI], death) were investigated (Table). Results Figure shows the breakdown by dose (60mg vs 30mg) and recommended (rec) vs non-recommended (non-rec) dosing. Patients on non-rec 30mg vs on rec 60mg edoxaban were older (mean ± SD: 74±9 vs 70±9 y); had lower creatinine clearance (72.2±20.6 vs 85.8±26.8 mL/min); and had more comorbidities, history of MB (2.1% vs 1.1%), and strokes (11.0% vs 8.6%). Non-rec 60mg vs rec 30mg patients were younger (75±9 vs 78±9 y), had fewer comorbidities, history of MB (1.2% vs 2.6%), and strokes (10.2% vs 16.4%). In non-rec 30mg vs rec 60mg, MB was not lower and ischaemic events were not higher. In non-rec 60mg vs rec 30mg, no increase in MB, CRNMB or ischaemic events was seen. Conclusion Edoxaban was prescribed at the label recommended dose in the vast majority of patients. Non-rec 30mg patients were sicker than rec 60mg patients while non-rec 60mg patients were less sick than rec 30mg patients. Overall event rates were low, and ischaemic event rates of non-rec 30mg and bleeding event rates of non-rec 60mg were not numerically higher than that of corresponding rec dosing groups. Clinical events, N (%/yr) No dose reduction criteria met ≥1 dose reduction criterion met Rec. 60 mg (N=12,708) Non-rec. 30 mg (N=3,016) Non-rec. 60 mg (N=1,640) Rec. 30 mg (N=9,459) Major bleeding (ISTH) 92 (0.77) 31 (1.13) 18 (1.19) 132 (1.61) ICH 31 (0.26) 5 (0.18) 1 (0.07) 38 (0.46) Major GI bleeding 32 (0.27) 21 (0.76) 6 (0.39) 81 (0.98) CRNMB 177 (1.48) 42 (1.53) 25 (1.65) 226 (2.76) Ischaemic stroke/TIA 113 (0.94) 20 (0.72) 16 (1.05) 126 (1.53) Haemorrhagic stroke 20 (0.17) 3 (0.11) 1 (0.07) 32 (0.39) MI 42 (0.35) 8 (0.29) 5 (0.33) 31 (0.38) Systemic embolism 8 (0.07) 1 (0.04) 1 (0.07) 12 (0.15) All-cause mortality 214 (1.78) 79 (2.86) 54 (3.54) 398 (4.82) CV mortality 99 (0.82) 37 (1.34) 21 (1.38) 142 (1.72) Funding Acknowledgement Type of funding source: Private compa