New 12-month analysis data from ETNA-AF non-interventional study show low bleeding and ICH rates in frail and ageing AF patients on LIXIANA®▼ (edoxaban) during routine clinical care

• Newly presented data provide reassurance around edoxaban use in vulnerable populations of frail, ageing and renally impaired patients
• Clinician’s perception of frailty found to potentially be a better marker of clinical outcomes than age

• The global ETNA-AF programme, which includes ETNA-AF-Europe, is the largest prospective, non-interventional study investigating a single DOAC to date

Munich, Germany (31 August 2020) – Daiichi Sankyo Europe, (hereafter, Daiichi Sankyo) today announced one-year results of four sub-analyses from the European and global ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) programme, a non-interventional safety study evaluating edoxaban treatment in routine clinical practice in >26,000 patients around the world with atrial fibrillation (AF).^1,2,3,4 New 12-month data from the European and global ETNA-AF registries showed rates of bleeding and intracranial haemorrhage (ICH) were considered low by the authors’ assessment in frail and ageing patients in routine clinical care.^1,2,3 Findings, which are part of the largest prospective, non-interventional study programme investigating a single direct oral anticoagulant (DOAC) in patients with non-valvular atrial fibrillation (NVAF) to date, are available virtually at the ESC Congress 2020, the annual meeting of the European Society of Cardiology, taking place 29 August – 01 September.

In vulnerable populations such as the ageing, frail and those with renal impairment, anticoagulation for stroke prevention is often not prescribed due to the risk of bleeding, despite these patients being among those most at risk for ischaemic events like stroke.⁵ However, outcomes from ETNA-AF reinforce the effectiveness and safety of edoxaban in these populations.^1,2

“Ageing and frail patients have been underrepresented in certain AF stroke prevention trials, leaving a lack of evidence to support routine DOAC use in these patients. However, these new data should provide clinicians with some confidence of edoxaban’s efficacy and safety profile to reduce the risk of stroke for the ageing and frail AF populations,” Dr Ameet Bakhai, Consultant Cardiologist &  Cardiovascular R&D Director Royal Free London NHS Trust, UK.

ETNA-AF-Europe Registry Outcomes: Frailty and renal function

Anticoagulation presents multiple challenges in patients who are frail, as well as those who are frail and have renal impairment.⁵ The first of the two data analyses from the 13,092 patient-wide ETNA-AF-Europe registry assessed key clinical outcomes and risk scores in frail and ageing patients versus non-frail or younger patients correspondingly.¹ Frailty – commonly defined as those at increased risk of disability, hospitalisation, and mortality⁶ – was determined by physician perception.¹

Results from 1,392 patients, who were considered frail, showed:¹

• Rates of intracranial haemorrhage (ICH) remained low by the investigators’ assessment, regardless of frailty status or age, despite frail patients being four times more likely to suffer mortality and presenting with higher rates of major bleeding compared to the non-frail cohort
• Per year, ICH occurred in 0.15% of patients in the frail cohort, compared to 0.27% of those in the non-frail cohort
• Per year, major bleeding occurred in 2.18% of patients in the frail cohort, compared to 0.95% of those in the non-frail cohort
• Per year, total mortality occurred in 10.43% of patients in the frail cohort, compared to 2.49% of those in the non-frail cohort

In addition, the analysis suggested that clinician’s perception of frailty appeared to be a better marker of clinical outcomes than age.¹

In the second analysis from the ETNA-AF-Europe registry, 13,021 patients with renal impairment were observed to evaluate baseline characteristics and assess follow-up outcomes at one-year.² The presence of AF is linked with a greater risk of developing moderate and severe renal impairment, and clinically, anticoagulation presents multiple challenges in patients with impaired renal function because the pharmacokinetic properties and bioavailability of the treatment are often altered in those patients.^7,8 Findings of this analysis indicated that across the three groups (moderate to severe renal disease [CrCl ≤50 mL/min], mild renal disease [CrCl 50–80 mL/min] and normal renal function [CrCl ≥80 mL/min]), who were categorised according to their creatinine clearance (CrCl) levels, patients treated with edoxaban had low rates of ICH and haemorrhagic stroke, by the investigators’ assessment, and these results were similar in patients across all groups studied.2 Regarding renal function, ICH occurred in 0.18%, 0.32% and 0.17% of patients annually, while haemorrhagic stroke occurred in 0.04%, 0.17% and 0.10% of patients in the group with moderate to severe renal disease, mild renal disease and normal renal function, respectively.²

Global ETNA-AF: Treatment of ageing patients

Findings from one of two global sub-analyses showed that at 12 months, rates of ICH were consistently low across all age groups, while CV mortality increased numerically with age, but to a lower extent than all-cause mortality.³ Additional findings from the global registry, assessing the safety and effectiveness of edoxaban given at the recommended or non-recommended dose in AF patients during one-year observation in routine clinical practice, showed that edoxaban is being prescribed at the label recommended dose in the vast majority of patients, but that non-recommended edoxaban dosage tends to occur more frequently when the CrCl or body weight was closer to the threshold of dose reduction.⁴

“AF is common in the ageing population as are comorbidities and higher rates of CV events, including bleeding, which all need to be managed with a great deal of consideration for the challenges they present for both clinicians and patients,” said Wolfgang Zierhut MD, Executive Director Medical Affairs and Head Thrombosis and Cardiovascular at Daiichi Sankyo Europe. “These latest data show the consistency of edoxaban treatment in providing benefits to a wide range of patients.

ETNA-AF is one of more than 10 randomised, controlled trials (RCTs), registries and non-randomised clinical studies that comprise the Edoxaban Clinical Research Programme.

All of the ETNA-AF non-interventional study data presented at ESC Congress 2020 can be found here.

Additional edoxaban data presented

In addition to ETNA-AF, data from multiple clinical studies from the Edoxaban Clinical Research Programme were also presented.