Evidence map›Paper›PMID 42489381›Full record

ArticleJACC. Advances2026

Heterogeneity of Treatment Effect of DOACs vs Warfarin in Atrial Fibrillation.

Samer Al Said, Andrea Bellavia, Eugene Braunwald, Elaine M Hylek, Michael G Palazzolo, Hwanhee Hong, Elliott M Antman, Anthony P Carnicelli, John W Eikelboom, Christopher B Granger and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. Advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
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.

Samer Al SaidTIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Andrea BellaviaTIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Eugene BraunwaldTIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Elaine M HylekDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
Michael G PalazzoloTIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Hwanhee HongDuke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
Elliott M AntmanTIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Anthony P CarnicelliDivision of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
John W EikelboomPopulation Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Christopher B GrangerDuke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
Manesh R PatelDuke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
Lars WallentinDepartment of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Christian T RuffTIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Robert P GiuglianoTIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Electronic address: rgiugliano@bwh.harvard.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDirect oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF). However, limited accessibility in resource-constrained settings makes it important to identify patient subgroups in whom VKAs may achieve comparable net clinical outcomes (NCOs).

objectivesThe purpose of this study was to identify AF patient subgroups and explore potential predictors of differential treatment benefit to inform anticoagulant selection where DOAC access is limited.

methodsIndividual patient data from the COMBINE-AF data set pooling 4 pivotal randomized trials of DOACs vs VKAs in AF were analyzed. Model-based clustering identified patient subgroups. Heterogeneity of treatment effects for the NCO-a composite of all-cause death, disabling or fatal stroke, and intracranial or fatal bleeding- was explored using Cox regression and gradient boosting analyses adapted for time-to-event data.

resultsA total of 58,634 patients were included (29,272 warfarin; 29,362 standard dose DOACs). Two subgroups were identified: a high-risk cluster (mean creatinine clearance 55.1 mL/min, age 75.6 years, body mass index [BMI] 26.6 kg/m

conclusionsRenal function, age, and BMI are key determinants of anticoagulant treatment benefit in AF. In regions with limited access to DOACs, these findings suggest that some lower-risk patient profiles may derive similar outcomes with VKAs, although differences were not statistically significant.

Indexed as

atrial fibrillationdirect oral anticoagulantsheterogeneity of treatment effectmachine learningrisk stratificationwarfarin

Identifiers

PMID42489381
PMCPMC13400104

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Registered trials

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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.