Evidence map›Paper›PMID 37042255›Full record

ArticleCirculation2023

Direct Oral Anticoagulants Versus Warfarin Across the Spectrum of Kidney Function: Patient-Level Network Meta-Analyses From COMBINE AF.

Josephine Harrington, Anthony P Carnicelli, Kaiyuan Hua, Lars Wallentin, Manesh R Patel, Stefan H Hohnloser, Robert P Giugliano, Keith A A Fox, Ziad Hijazi, Renato D Lopes and 3 more

Open access · bronzeAbstract readNetwork Meta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 6 pooled it
16.2field-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.

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

49 citing papers in PubMed, 6 syntheses or guidelines pooled it, 74 citations in OpenAlex.

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  10. Managing bleeds on anticoagulant therapy: a practical guide for clinicians.European heart journal. Acute cardiovascular care · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 4 countries.

Josephine HarringtonDepartment of Medicine, Division of Cardiology, Duke University, Durham, NC (J.H., M.R.P., R.D.L., S.D.P., C.B.G.).ORCID 0000-0001-5169-117X
Anthony P CarnicelliDepartment of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston (A.P.C.).ORCID 0000-0002-9805-4562
Kaiyuan HuaDuke Clinical Research Institute, Durham, NC (J.H., K.H., M.R.P., R.D.L., S.D.P., H.H., C.B.G.).ORCID 0000-0003-4841-8820
Lars WallentinUppsala Clinical Research Center (L.W.), Uppsala University, Sweden.ORCID 0000-0003-0378-6531
Manesh R PatelDepartment of Medicine, Division of Cardiology, Duke University, Durham, NC (J.H., M.R.P., R.D.L., S.D.P., C.B.G.).ORCID 0000-0002-2393-0855
Stefan H HohnloserDepartment of Cardiology, JW Goethe University, Frankfurt, Germany (S.H.H.).ORCID 0000-0001-5030-3315
Robert P GiuglianoTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.P.G.).ORCID 0000-0003-4110-7675
Keith A A FoxDivision of Medical and Radiological Sciences, University of Edinburgh, UK (K.A.A.F.).ORCID 0000-0002-0140-2752
Ziad HijaziDepartment of Medical Sciences, Cardiology (L.W., Z.H.), Uppsala University, Sweden.ORCID 0000-0002-7420-743X
Renato D LopesDepartment of Medicine, Division of Cardiology, Duke University, Durham, NC (J.H., M.R.P., R.D.L., S.D.P., C.B.G.).ORCID 0000-0003-2999-4961
Sean D PokorneyDepartment of Medicine, Division of Cardiology, Duke University, Durham, NC (J.H., M.R.P., R.D.L., S.D.P., C.B.G.).ORCID 0000-0002-4345-0816
Hwanhee HongDuke Clinical Research Institute, Durham, NC (J.H., K.H., M.R.P., R.D.L., S.D.P., H.H., C.B.G.).
Christopher B GrangerDepartment of Medicine, Division of Cardiology, Duke University, Durham, NC (J.H., M.R.P., R.D.L., S.D.P., C.B.G.).ORCID 0000-0002-0045-3291
Duke University · USClinical Research Institute · USUppsala University · SEBrigham and Women's Hospital · USGoethe University Frankfurt · DEMedical University of South Carolina · USUniversity of Edinburgh · GB

Funding

Postdoctoral Training in Cardiovascular Clinical ResearchT32HL069749 · NHLBI · DUKE UNIVERSITY · PI MARK, DANIEL B · 2003 to 2023
$6.7M
NHLBI NIH HHS T32 HL069749
6 · The paper itself

Abstract

backgroundThere is uncertainty surrounding the use of direct oral anticoagulants (DOACs) in patients with kidney dysfunction.

methodsUsing the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY [Randomized Evaluation of Long-term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), we performed an individual patient-level network meta-analysis to evaluate the safety and efficacy of DOACs versus warfarin across continuous creatinine clearance (CrCl). A multivariable Cox model including treatment-by-CrCl interaction with random effects was fitted to estimate hazard ratios for paired treatment strategies (standard-dose DOAC, lower-dose DOAC, and warfarin). Outcomes included stroke and systemic embolism (S/SE), major bleeding, intracranial hemorrhage (ICH), and death.

resultsAmong 71 683 patients (mean age, 70.6±9.4 years; 37.3% female; median follow-up, 23.1 months), the mean CrCl was 75.5±30.5 mL/min. The incidence of S/SE, major bleeding, ICH, and death increased significantly with worsening kidney function. Across continuous CrCl values down to 25 mL/min, the hazard of major bleeding did not change for patients randomized to standard-dose DOACs compared with those randomized to warfarin (

conclusionsStandard-dose DOACs are safer and more effective than warfarin down to a CrCl of at least 25 mL/min. Lower-dose DOACs do not significantly lower the incidence of bleeding or ICH compared with standard-dose DOACs but are associated with a higher incidence of S/SE and death. These findings support the use of standard-dose DOACs over warfarin in patients with kidney dysfunction.

Indexed as

Atrial FibrillationEmbolismStrokeAdministration, OralAgedAged, 80 and overAnticoagulantsFactor XaFemaleHemorrhageHumansIntracranial HemorrhagesKidneyMaleMiddle AgedRandomized Controlled Trials as TopicAnticoagulantsFactor XaWarfarinanticoagulantsatrial fibrillationkidney

Identifiers

PMID37042255
PMCPMC10309661
OpenAlexW4365136260

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.