DAIICHI-SANKYO

Daiichi Sankyo Europe, (hereafter, Daiichi Sankyo) today announced a wealth of new edoxaban data being presented at ESC Congress 2021, organised by the European Society of Cardiology. These include insights from routine clinical practice via the ETNA-AF Registry, which reaffirm the efficacy and safety profile of edoxaban seen in randomised clinical trials across a range of atrial fibrillation (AF) patient populations. In addition, results from the ENVISAGE-TAVI AF study, presented as a Hot Line session during the congress, compared the efficacy and safety of edoxaban with vitamin-K-antagonists (VKA) in patients with AF having undergone successful transcatheter aortic valve implantation (TAVI).¹ Findings from the trial were simultaneously published in The New England Journal of Medicine (NEJM) .

The revised 2021 EHRA^* Practical Guide on the Use of NOACs^† in Patients with Atrial Fibrillation (AF), which was published earlier this year (April), recommends the use of NOACs as first-line treatment of patients with AF and includes specific guidance around treating complex AF patient populations, such as those with different levels of frailty and those with renal impairment.² The data presented today further complement the recommendations of the Practical Guide for the treatment of AF patients using NOACs.

“These new data, in addition to the recently updated EHRA Practical Guide on the use of NOACs in AF, provide long-awaited scientific evidence that the clinical community will welcome as a huge support in helping treat these complex patient populations with AF,” said Prof. Hein Heidbuchel, Chair of Cardiology at Antwerp University, Belgium, and immediate Past-President of the European Heart Rhythm Association (EHRA). “It is acknowledged across the world now that NOACs are the preferred choice of treatment for patients with AF. Having additional data to help guide healthcare professionals in the specifics of anticoagulating these patient populations will bring further clarity and confidence to the clinical community.”

ETNA-AF-Europe Registry: Worsening renal function (WRF) and frailty

Key ePosters presented from the ETNA-AF-Europe Registry include the evaluation of the degree of worsening renal function (WRF) in AF patients treated with edoxaban after two-years of follow-up and an investigation of clinical outcomes of patients with vs. without WRF. Results from 9,084 patients included in this subgroup analysis showed that there is a low risk of WRF in AF patients treated with edoxaban over a two-year period, with the majority of the edoxaban-treated patients not experiencing WRF (89.9%). Results also found that:³

• Patients with WRF had higher mortality than those without (all-cause mortality: 3.78% vs. 1.90%; cardiovascular death: 2.06% vs. 0.92%, respectively).
• Patients with WRF had numerically higher major bleeding and stroke rates vs. those without WRF.
• Importantly, intracranial haemorrhage rates remained low irrespective of WRF (0.17% in those with WRF vs. 0.19% in those without).

A second key ePoster analysed effectiveness and safety outcomes in subjectively vs. objectively frail patients in the overall population. Results showed that the presence of frailty (either subjective or objective) predicts cardiovascular (CV) events in anticoagulated patients with AF and is associated with a worse prognosis of CV events.⁴ These results support the idea that a comprehensive assessment of frailty could improve the routine care of patients with AF and are in line with the ESC 2020 guidelines, which highlight the importance of including assessment and evaluation of frailty into the integrated management of AF.⁵

ENVISAGE-TAVI AF study

In addition, results from the ENVISAGE-TAVI AF study were presented as a Hot Line session during the ESC congress 2021. In this multinational, randomised, Phase 3b study, 1,426 elderly patients with multiple comorbidities were included and followed for up to three years.^1,6 The study results suggest that edoxaban is an appropriate treatment option for AF patients with severe aortic stenosis following successful TAVI.^1,6 To date, this is the only sufficiently large and statistically powered study that compares a non-vitamin K antagonist oral anticoagulant (NOAC) with VKAs in AF patients after TAVI.^1,6

“TAVI is an established treatment option for patients with severe aortic valve stenosis, including those with AF and multiple comorbidities,” said George Dangas, MD, PhD, Professor of Medicine (Cardiology) and Director of Cardiovascular Innovation at the Zena and Michael A. Wiener Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai. “In AF patients, anticoagulation is required to prevent stroke, which can be a devastating complication following TAVI. ENVISAGE-TAVI AF shows that treatment with edoxaban can be valuable in the management of this high-risk population of AF patients after TAVI.”

The study met its primary endpoint of edoxaban being noninferior to VKAs for the composite of net adverse clinical events (NACE), which included all-cause mortality, myocardial infarction, ischaemic stroke, systemic thromboembolism, valve thrombosis, and International Society on Thrombosis and Haemostasis (ISTH)-defined major bleeding.^1,6 NACE occurred in 170 edoxaban-treated patients (17.3% per year) and, similarly, in 157 VKA-treated patients (16.5% per year).^1,6

Edoxaban also showed numerically lower rates of all-cause mortality and ischemic stroke (two of the six individual clinical events included in the composite of NACE):^1,6

• All-cause mortality occurred in 85 edoxaban-treated patients and 93 VKA-treated patients (7.8% versus 9.1% per year, respectively).
• Ischaemic stroke occurred in 22 edoxaban-treated patients and 28 VKA-treated patients (2.1% versus 2.8% per year, respectively).

The study did not meet its primary safety endpoint of ISTH-defined major bleeding, due to more gastrointestinal (GI) bleeds in the edoxaban arm.^1,6 Other major bleeding events, including intracranial haemorrhage (ICH), as well as fatal and life-threatening bleeds, were similarly rare in both the edoxaban and VKA treatment arms.^1,6

Major bleeding occurred in 98 edoxaban-treated patients and 68 VKA-treated patients (9.7% vs. 7.0% per year, respectively), which included the following:^1,6

• Major GI bleeding occurred in 56 edoxaban-treated patients and 27 VKA-treated patients (5.4% vs. 2.7% per year, respectively).
• ICH occurred in 16 edoxaban-treated patients and 21 VKA-treated patients (1.5% vs. 2.1% per year, respectively).
• Fatal bleeding occurred in 11 edoxaban-treated patients and 10 VKA-treated patients (1.0% vs. 1.0% per year, respectively).
• Life threatening bleeding occurred in 17 edoxaban-treated patients and 19 VKA-treated patients (1.6% vs. 1.9% per year, respectively).

“These findings present evidence that edoxaban is an appropriate treatment option in AF patients post-TAVI, who are typically elderly and frail,” said Prof. Nicolas Van Mieghem, global co-lead investigator from Erasmus University Medical Center in Rotterdam, The Netherlands. “We found more major bleedings with edoxaban driven by more gastrointestinal bleedings that were well managed with no significant difference in intracranial or fatal bleedings.”

ETNA-AF-Europe and the ENVISAGE TAVI-AF study are part of EDOSURE, which is an extensive clinical research programme for edoxaban consisting of more than 10 randomised controlled trials, registries and non-interventional studies in a broad range of cardiovascular conditions, patient types and clinical settings in AF and venous thromboembolism (VTE), involving over 100,000 patients worldwide.

Additional edoxaban data presented at ESC Congress 2021

ETNA-AF-Europe		Age-adjusted risk factors are independently associated with an increased risk of ischaemic stroke, transient ischaemic stroke and systemic embolism in the ETNA-AF-Europe registry (link to data here )		De Caterina R, et al.
		Age-adjusted risk factors are independently associated with an increased risk of major bleeding during the two-year follow-up of the ETNA-AF-Europe registry (link to data here )		Kirchhof P, et al.
Global ETNA-AF		Temporal trend of clinical events in patients with atrial fibrillation on edoxaban therapy: Results from the noninterventional Global ETNA-AF program (link to data here )		Dinshaw L, et al.
		Edoxaban treatment in real-world practice is highly concordant with ESC atrial fibrillation guidelines: results from the non-interventional global ETNA-AF program (link to data here )		Morrone D, et al.
		Effectiveness and safety of edoxaban in atrial fibrillation patients from the ETNA-AF global registry (link to data here )		De Caterina R, et al.
ANAFIE		Impact of polypharmacy on clinical outcomes in elderly patients with nonvalvular atrial fibrillation: sub-analysis of the ANAFIE Registry (link to data here )		Yamashita T.
		Predictors for major bleeding in elderly (75 years and over) patients with nonvalvular atrial fibrillation at high risk of bleeding: sub-analysis of the ANAFIE Registry (link to data here )		Okumura K.
		Association between renal function and clinical outcomes in elderly patients with nonvalvular atrial fibrillation: sub-analysis of the ANAFIE Registry (link to data here )		Shimizu W.
		Real-world clinical outcomes and anticoagulant therapy in elderly non-valvular atrial fibrillation patients with heart failure: sub-analysis of the ANAFIE Registry (link to data here )		Ikeda S, Hiasa K, Tsutsui H.
ENGAGE AF-TIMI 48		Epistaxis in anticoagulated patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial (link to data here )		Semco RS, et al.

-ENDS-

About ETNA-AF: https://www.daiichi-sankyo.eu/media/edoxaban-info/

About ENVISAGE-TAVI AF: https://www.daiichi-sankyo.eu/media/edoxaban-info/

About atrial fibrillation: https://www.daiichi-sankyo.eu/media/edoxaban-info/

About edoxaban: https://www.daiichi-sankyo.eu/media/edoxaban-info/

About the Edoxaban Clinical Research Programme, EDOSURE: https://www.daiichi-sankyo.eu/media/edoxaban-info/

About Daiichi Sankyo

Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realise our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.”

For more information, please visit www.daiichi-sankyo.eu .

Forward-looking statements: https://www.daiichi-sankyo.eu/media/edoxaban-info/

References

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* European Heart Rhythm Association
† Non-Vitamin K Antagonist Oral Anticoagulants

¹ Dangas G. ENVISAGE-TAVI AF: edoxaban vs. vitamin K antagonists after TAVI in patients with atrial fibrillation. Hot Line Presentation at ESC Congress 2021, 27–30 August.
² Steffel J, et al. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. EP Europace . 2021; euab065, https://doi.org/10.1093/europace/euab065 .
³ Gwechenberger M, et al . Low rate of worsening renal function during 2 years of treatment with edoxaban in patients from the ETNA-AF-Europe study. Poster 84715. Presented at ESC Congress 2021.
⁴ Diemberger I, et al . The impact of subjective vs objective frailty on the effectiveness and safety outcomes in patients from ETNA-AF-Europe registry. Poster 84668. Presented at ESC Congress 2021.
⁵ Hindricks G, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J . 2021;42:373–498.
⁶ Van Mieghem NM, et al. Edoxaban vs Vitamin K Antagonist for Atrial Fibrillation After Transcatheter Aortic Valve Replacement. N Engl J Med . 2021. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa2111016 Last accessed August 2021.

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