Evidence map›Paper›PMID 27207971›Full record

Trial reportJournal of the American Heart Association2016

Efficacy and Safety of Edoxaban in Elderly Patients With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial.

Eri Toda Kato, Robert P Giugliano, Christian T Ruff, Yukihiro Koretsune, Takeshi Yamashita, Robert Gabor Kiss, Francesco Nordio, Sabina A Murphy, Tetsuya Kimura, James Jin and 4 more

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

Trial report in Journal of the American Heart Association, 2016. 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 115 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 12 pooled it
23.8field-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

115 citing papers in PubMed, 12 syntheses or guidelines pooled it, 279 citations in OpenAlex.

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55 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

14 authors at 6 institutions in 2 countries.

Eri Toda KatoTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA Tokai University Hospital, Isehara, Japan.
Robert P GiuglianoTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA rgiugliano@partners.org.
Christian T RuffTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Yukihiro KoretsuneOsaka National Hospital, Osaka, Japan.
Takeshi YamashitaThe Cardiovascular Institute, Tokyo, Japan.
Robert Gabor KissMilitary Hospital, Budapest, Hungary.
Francesco NordioTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Sabina A MurphyTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Tetsuya KimuraDaiichi Sankyo, Tokyo, Japan.
James JinDaiichi Sankyo, Parsippany, NJ.
Hans LanzDaiichi Sankyo, Parsippany, NJ.
Michele MercuriDaiichi Sankyo, Parsippany, NJ.
Eugene BraunwaldTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Elliott M AntmanTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Thrombolysis in Myocardial Infarction Study Group · USDaiichi Sankyo (United States) · USBrigham and Women's Hospital · USCardiovascular Institute Hospital · JPDaiichi-Sankyo (Japan) · JPOsaka National Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundElderly patients with atrial fibrillation are at higher risk of both ischemic and bleeding events compared to younger patients. In a prespecified analysis from the ENGAGE AF-TIMI 48 trial, we evaluate clinical outcomes with edoxaban versus warfarin according to age. METHODS AND

resultsTwenty-one thousand one-hundred and five patients enrolled in the ENGAGE AF-TIMI 48 trial were stratified into 3 prespecified age groups: <65 (n=5497), 65 to 74 (n=7134), and ≥75 (n=8474) years. Older patients were more likely to be female, with lower body weight and reduced creatinine clearance, leading to higher rates of edoxaban dose reduction (10%, 18%, and 41% for the 3 age groups, P<0.001). Stroke or systemic embolic event (1.1%, 1.8%, and 2.3%) and major bleeding (1.8%, 3.3%, and 4.8%) rates with warfarin increased across age groups (Ptrend<0.001 for both). There were no interactions between age group and randomized treatment in the primary efficacy and safety outcomes. In the elderly (≥75 years), the rates of stroke/systemic embolic event were similar with edoxaban versus warfarin (hazard ratio 0.83 [0.66-1.04]), while major bleeding was significantly reduced with edoxaban (hazard ratio 0.83 [0.70-0.99]). The absolute risk difference in major bleeding (-82 events/10 000 pt-yrs) and in intracranial hemorrhage (-73 events/10 000 pt-yrs) both favored edoxaban over warfarin in older patients.

conclusionsAge has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation. Given the higher rates of bleeding and death with increasing age, treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with edoxaban versus warfarin in younger patients. CLINICAL

trial registrationURL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391.

Indexed as

AgedAge FactorsAnticoagulantsAtrial FibrillationDouble-Blind MethodEmbolismFactor Xa InhibitorsFemaleHemorrhageHumansMaleMiddle AgedPyridinesStrokeThiazolesTreatment OutcomeAnticoagulantsedoxabanFactor Xa InhibitorsPyridinesThiazolesWarfarinantithromboticbleedingdeathelderlystroke

Identifiers

PMID27207971
PMCPMC4889207
OpenAlexW2402689780

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.