Evidence map›Paper›PMID 41677103›Full record

SynthesisClinical cardiology2026

Dose-Response Efficacy and Safety of Factor XI/XIa Inhibitors in Atrial Fibrillation; a Systematic Review and Meta-Analysis With Subgroup Exploration and Trial Sequential Validation.

Muhammad Aqib Faizan, Tooba Rehman, Mrunalini Dandamudi, Jaivardhan A Menon, Victoria Zecchin Ferrara, Zeyad Kholeif, Alina Tanvir, Fatima Saeed, Jibran Ikram, Moiuz Chaudhri and 7 more

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Clinical cardiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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

17 authors.

Muhammad Aqib FaizanGomal Medical College, Khyber Medical University, Peshawar, Pakistan.ORCID https://orcid.org/0009-0002-6023-3992
Tooba RehmanGomal Medical College, Khyber Medical University, Peshawar, Pakistan.
Mrunalini DandamudiMontefiore Einstein Medical Center, Bronx, New York, USA.
Jaivardhan A MenonDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Victoria Zecchin FerraraFaculty of Medicine and Surgery, University of Padua, Padua, Italy.
Zeyad KholeifCardiovascular department, Mayo Clinic, Rochester, Minnesota, USA.
Alina TanvirKing Edward Medical University, Lahore, Pakistan.
Fatima SaeedMassachusetts General Hospital, Boston, USA.
Jibran IkramCardiovascular Medicine Department, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID https://orcid.org/0009-0003-6653-0661
Moiuz ChaudhriHackensack Meridian Ocean University Medical Center, Brick, New Jersey, USA.
Carlos EspicheMontefiore Einstein Medical Center, Bronx, New York, USA.
Main Muhammad Salman AslamDepartment of Pulmonary and Critical Care Medicine, University of Michigan Ann Arbor, Michigan, USA.
Zainab HumayunUniversity of Missouri-Kansas City, Missouri, USA.
Ahmad Mustafa KhalidAbbottabad International Medical College, Abbottabad, Pakistan.
Saad Ahmad WaqasDow University of Health Sciences, Karachi, Pakistan.ORCID https://orcid.org/0009-0008-9051-6081
Raheel AhmadImperial College London, London, UK.
Luis CernaGeorge Washington University Hospital, Washington, DC, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFactor XI/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta-analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization.

methodsA systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all-cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel-Haenszel random-effects model. Heterogeneity was evaluated with the I² statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed.

resultsThree RCTs including 16,772 patients (mean age 73 years, CHA₂DS₂-VASc 3.9-5) were analyzed. Factor XI/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36-0.46, I² = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62-4.46), particularly with asundexian 50 mg (RR: 4.02). No significant differences were observed in all-cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large-scale studies.

conclusionFactor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.

Indexed as

AnticoagulantsAtrial FibrillationFactor XIFactor XIaStrokeDose-Response Relationship, DrugHemorrhageHumansRandomized Controlled Trials as TopicRisk FactorsTreatment OutcomeAnticoagulantsFactor XIFactor XIaanticoagulationatrial fibrillationdirect oral anticoagulantsfactor XI/XIa

Identifiers

PMID41677103
PMCPMC12895463

What OpenQuestion holds

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LicenceCC BY
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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.