P4756Stroke and bleeding in low, intermediate and high risk patients with atrial fibrillation treated with edoxaban: Results of the ETNA-AF Europe registry

Abstract

Background Edoxaban, a direct FXa inhibitor, has been proven non-inferior in efficacy and safer compared to warfarin in the ENGAGE AF-TIMI 48 trial. In routine care, the safety of edoxaban has not been formally established. ETNA-AF-Europe is a multinational, multi-centre, post-authorisation, observational study (NCT02944019) conducted in 825 sites in 10 European countries. Here 13,980 edoxaban-treated patients with AF were enrolled between November 2016 and February 2018, and will be followed-up for 4 years. Methods 7,672 patients (73.4±9.26 years, 57.5% male) enrolled in the ETNA-AF Europe registry completed the one-year follow-up and were stratified into low-, intermediate- and high-risk for stroke and bleeding using the CHA2DS2-VASc and HASBLED score, respectively. We here analysed the occurrence of stroke, bleeding, intracranial haemorrhage and mortality in such categories. Results The mean CHA2DS2-VASc score at baseline was 3.1±1.38 and the mean HAS-BLED score was 2.5±1.1. Not surprisingly, patients at higher risk were older, had a lower body weight, more comorbidities, and a lower creatinine clearance. A higher proportion of patients at high risk received the reduced 30 mg edoxaban dose. Overall, the yearly event rates of stroke, intracranial haemorrhage, major bleeding and death were low. However, these rates increased consistently in patients with higher stroke and bleeding risks. Residual stroke risk on anticoagulation was comparable to the risk of major bleeding (Table 1). Outcomes by stroke and bleeding risk CHA2DS2-VASc: mean 3.1±1.38 HAS-BLED: mean 2.5±1.1 All patients Low risk (0, 1 if female) Intermediate risk (1, 2 if female) High risk (≥2, 3 if female) Low risk (0, 1) Intermediate risk (2, 3) High risk (≥4) Patients, N 233 1,133 6,304 1,224 4,932 1,516 7,672 First occurrence of outcomes, n (%/year) All-cause mortality 2 (0.92%) 12 (1.11%) 242 (4.09%) 14 (1.21%) 161 (3.47%) 82 (5.78%) 257 (3.56%) Intracranial haemorrhage 0 (0.00%) 1 (0.09%) 19 (0.32%) 2 (0.17%) 10 (0.22%) 8 (0.56%) 20 (0.28%) Major bleeding 0 (0.00%) 6 (0.56%) 62 (1.05%) 2 (0.17%) 43 (0.93%) 23 (1.63%) 68 (0.95%) Stroke/SEE 0 (0.00%) 4 (0.37%) 59 (1.00%) 3 (0.26%) 41 (0.89%) 19 (1.34%) 63 (0.88%) SEE, systemic embolic event. Conclusions In this unselected cohort of patients with AF anticoagulated with edoxaban, high CHA2DS2-VASc and HAS-BLED scores were associated with higher risks of stroke, bleeding and death. Indirectly compared with the expected rates in non-anticoagulated patients, our data underpin the value of anticoagulants such as edoxaban in patients at high risk of stroke and bleeding. Acknowledgement/Funding The ETNA-AF Registry was funded by Daiichi Sankyo Europe GmbH, Munich, Germany.

Prescribing Patterns and Outcomes of Edoxaban in Atrial Fibrillation Patients From Asia ― One-Year Data From the Global ETNA-AF Program ―

“…The proportion of patients receiving the nonrecommended 30-mg dose reported here is consistent with previous observations from other similar studies in routine care conducted in Taiwan and South Korea, but slightly higher than the nonrecommended dosing observed in Europe and Japan. 16,21,24,25 In the retrospective, observational study of 11,275 patients from Taiwan receiving NOACs, approximately 32% of patients received a nonrecommended dose (27% under-vs. 5% overdosed); the proportion of patients receiving the recommended dose varied for rivaroxaban (81%), edoxaban (67%), apixaban (65%), and dabigatran (44%). 16,26,27 The CODE-AF registry evaluated NOAC label adherence in 3,080 South Korean patients with AF in routine clinical practice; 61.9% received the recommended NOAC dose, and 38.1% received the nonrecommended NOAC dose (36.4% under-vs. 1.6% overdosed).…”

“…[1][2][3][4][5][6] In contrast to physicians in non-Asian countries, physicians in Asian countries more frequently prescribe a reduced dose of NOACs, 7, 8 which may be partly attributed to the lower mean body weight and higher risk of bleeding noninterventional, and regional studies from Europe, Japan, and other Asian countries/regions (South Korea/ Taiwan [NCT02951039], Hong Kong [NCT03247582], and Thailand [NCT03247569]). 18,20, 21 The ETNA-AF study protocols received the appropriate review board approvals. 19, 20 The program complied with the latest version of the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practices standards.…”

Situación actual de los anticoagulantes orales de acción directa en atención primaria de España. Posicionamiento de SEMERGEN en 2023

“…ETNA-AF-Europe es un registro internacional de pacientes en tratamiento con edoxabán en la práctica clínica, y 13.092 pacientes completaron el primer año de seguimiento. Las tasas anuales de ictus o de embolia sistémica en estos pacientes fueron 0,82%/año, de hemorragia mayor 1,05%/año, de hemorragia intracraneal 0,24%/año, de muerte cardiovascular 1,64%/año y de muerte por cualquier causa 3,50%/año 69 . En resumen, los registros internacionales confirman la efectividad y la seguridad de los ACOD en la práctica clínica, indicando que el beneficio de los ACOD frente a los AVK mostrado en los ensayos clínicos pivotales se puede extender a los pacientes de vida real.…”