Evidence map›Paper›PMID 33357217›Full record

Trial reportBMC medicine2020

Clinical outcomes in patients with atrial fibrillation and frailty: insights from the ENGAGE AF-TIMI 48 trial.

Chris Wilkinson, Jianhua Wu, Samuel D Searle, Oliver Todd, Marlous Hall, Vijay Kunadian, Andrew Clegg, Kenneth Rockwood, Chris P Gale

Registry-linked trialOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMC medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00781391 (A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Multi-Center, Multi-National Study for Evaluation of Efficacy and Safety of Edoxaban), which is not on this map. Cited by 62 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 5 pooled it
15.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00781391 phase3completednot on this map

A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Multi-Center, Multi-National Study for Evaluation of Efficacy and Safety of Edoxaban (DU-176b) Versus Warfarin In Subjects With Atrial Fibrillation - Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation (ENGAGE - AF TIMI - 48)

TypeinterventionalSponsorDaiichi SankyoRan2008 to 2013Enrolled21,105ConditionsStroke, Atrial Fibrillation, EmbolismArmswarfarin tablets, Edoxaban tablets (high dose regimen-60mg), Edoxaban tablets (low dose regimen-30mg), placebo warfarin, placebo edoxaban
3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 5 syntheses or guidelines pooled it, 109 citations in OpenAlex.

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  12. Clinical outcomes after catheter ablation for atrial fibrillation in elderly patients: a meta-analysis with time-to-event data reconstruction.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2026
    Review
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  14. Observational
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  17. Sarcopenia in atrial fibrillation: a risk factor for adverse outcomes in a UK Biobank study.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025
    Article
  18. Review
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Chris WilkinsonPopulation Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. Chris.Wilkinson@newcastle.ac.uk.ORCID 0000-0003-0748-0150
Jianhua WuLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Samuel D SearleMRC Unit for Lifelong Health and Ageing, University College London, London, UK.
Oliver ToddLeeds Institute for Data Analytics, University of Leeds, Leeds, UK.
Marlous HallLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Vijay KunadianTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Andrew CleggAcademic Unit for Ageing and Stroke Research, University of Leeds, Leeds, UK.
Kenneth RockwoodMRC Unit for Lifelong Health and Ageing, University College London, London, UK.
Chris P GaleLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
University of Leeds · GBDalhousie University · CANewcastle University · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GB

Funding

British Heart Foundation CS/15/7/31679The Dunhill Medical Trust RTF107/0117Wellcome Trust 206470/Z/17/Z
6 · The paper itself

Abstract

backgroundAtrial fibrillation (AF) is common in older people with frailty and is associated with an increased risk of stroke and systemic embolism. Whilst oral anticoagulation is associated with a reduction in this risk, there is a lack of data on the safety and efficacy of direct oral anticoagulants (DOACs) in people with frailty. This study aims to report clinical outcomes of patients with AF in the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial by frailty status.

methodsPost hoc analysis of 20,867 participants in the ENGAGE AF-TIMI 48 trial, representing 98.8% of those randomised. This double-blinded double-dummy trial compared two once-daily regimens of edoxaban (a DOAC) with warfarin. Participants were categorised as fit, living with pre-frailty, mild-moderate, or severe frailty according to a standardised index, based upon the cumulative deficit model. The primary efficacy endpoint was stroke or systemic embolism and the safety endpoint was major bleeding.

resultsA fifth (19.6%) of the study population had frailty (fit: n = 4459, pre-frailty: n = 12,326, mild-moderate frailty: n = 3722, severe frailty: n = 360). On average over the follow-up period, the risk of stroke or systemic embolism increased by 37% (adjusted HR 1.37, 95% CI 1.19-1.58) and major bleeding by 42% (adjusted HR 1.42, 1.27-1.59) for each 0.1 increase in the frailty index (four additional health deficits). Edoxaban was associated with similar efficacy to warfarin in every frailty category, and a lower risk of bleeding than warfarin in all but those living with severe frailty.

conclusionsEdoxaban was similarly efficacious to warfarin across the frailty spectrum and was associated with lower rates of bleeding except in those with severe frailty. Overall, with increasing frailty, there was an increase in stroke and bleeding risk. There is a need for high-quality, frailty-specific population randomised control trials to guide therapy in this vulnerable population.

trial registrationClinicalTrials.gov NCT00781391 . First registered on 28 October 2008.

Indexed as

AdultAgedAged, 80 and overAnticoagulantsAtrial FibrillationBlood CoagulationDouble-Blind MethodDrug Administration ScheduleFactor Xa InhibitorsFemaleFollow-Up StudiesFrailtyHemorrhageHumansMaleMiddle AgedAnticoagulantsedoxabanFactor Xa InhibitorsPyridinesThiazolesWarfarinAnticoagulationAtrial fibrillationClinical trialFrailtyStroke

Identifiers

PMID33357217
PMCPMC7758931
OpenAlexW3108889960

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.