Evidence map›Paper›PMID 34985309›Full record

ArticleCirculation2022

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex.

Anthony P Carnicelli, Hwanhee Hong, Stuart J Connolly, John Eikelboom, Robert P Giugliano, David A Morrow, Manesh R Patel, Lars Wallentin, John H Alexander, M Cecilia Bahit and 23 more

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

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 195 papers, 21 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
195citing papers in PubMed, 21 pooled it
53.0field-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

195 citing papers in PubMed, 21 syntheses or guidelines pooled it, 349 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Guideline
  13. Guideline
  14. Pooled it
  15. Pooled it
  16. A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Pooled it
  17. Efficacy and Safety of Direct Oral Anticoagulants Versus Standard Anticoagulation for Thromboprophylaxis in Nephrotic Syndrome: A Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Pooled it
  18. Evaluating the Efficacy and Safety of Direct Oral Anticoagulants Compared to Vitamin K Antagonists in Patients with Antiphospholipid Syndrome: Updated Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Pooled it
  19. Direct Oral Anticoagulants Versus Vitamin K Antagonists in Cerebral Venous Thrombosis: A Systematic Review and Meta-Analysis of 4,929 Patients.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Pooled it
  20. Anticoagulation Timing After Stroke in Atrial Fibrillation: Evidence from a Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Pooled it

135 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 14 institutions in 9 countries.

Anthony P CarnicelliDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.ORCID 0000-0002-9805-4562
Hwanhee HongDuke Clinical Research Institute (A.P.C., H.H., M.R.P., J.H.A., K.H., R.D.L., J.P.P., D.W., C.B.G.), Duke University, Durham, NC.
Stuart J ConnollyDepartment of Medicine, McMaster University, Ontario, Canada (S.J.C., J.E.).
John EikelboomDepartment of Medicine, McMaster University, Ontario, Canada (S.J.C., J.E.).
Robert P GiuglianoDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.P.G., D.A.M., E.A.B., J.K., C.T.R.).ORCID 0000-0003-4110-7675
David A MorrowThrombolysis in Myocardial Infarction Study Group, Boston, MA (R.P.G., D.A.M., E.A.B., C.T.R.).ORCID 0000-0002-9589-5382
Manesh R PatelDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.ORCID 0000-0002-2393-0855
Lars WallentinDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.
John H AlexanderDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.ORCID 0000-0002-1444-2462
M Cecilia BahitDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.ORCID 0000-0001-6179-4076
Alexander P BenzPopulation Health Research Institute, Hamilton Health Sciences, Ontario, Canada (S.J.C., J.E., A.P.B., L.D.).ORCID 0000-0003-2555-1266
Erin A BohulaDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.P.G., D.A.M., E.A.B., J.K., C.T.R.).ORCID 0000-0002-5559-8172
Tze-Fan ChaoDivision of Cardiology, Taipei Veterans General Hospital, Taiwan (T.-F.C.).
Leanne DyalPopulation Health Research Institute, Hamilton Health Sciences, Ontario, Canada (S.J.C., J.E., A.P.B., L.D.).
Michael EzekowitzDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.ORCID 0000-0003-3623-2252
Keith A A FoxCenter for Cardiovascular Science, University of Edinburgh, Scotland (K.A.A.F.).ORCID 0000-0002-0140-2752
Baris GencerDivision of Cardiology, Geneva University Hospitals, Geneva, Switzerland (B.G.).ORCID 0000-0002-8954-9694
Jonathan L HalperinDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.ORCID 0000-0002-8318-5471
Ziad HijaziUppsala Clinical Research Center and Department of Medical Sciences (L.W., Z.H., J.O.), Uppsala University, Sweden.ORCID 0000-0002-7420-743X
Stefan H HohnloserDepartment of Cardiology, JW Goethe University, Frankfurt, Germany (S.H.H.).ORCID 0000-0001-5030-3315
Kaiyuan HuaDuke Clinical Research Institute (A.P.C., H.H., M.R.P., J.H.A., K.H., R.D.L., J.P.P., D.W., C.B.G.), Duke University, Durham, NC.
Elaine HylekDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.
Eri Toda KatoDepartment of Cardiology, Kyoto University, Japan (E.T.K.).
Julia KuderDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.P.G., D.A.M., E.A.B., J.K., C.T.R.).
Renato D LopesDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.ORCID 0000-0003-2999-4961
Kenneth W MahaffeyStanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, CA (K.W.M.).
Jonas OldgrenUppsala Clinical Research Center and Department of Medical Sciences (L.W., Z.H., J.O.), Uppsala University, Sweden.
Jonathan P PicciniDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.ORCID 0000-0003-0772-2404
Christian T RuffDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.P.G., D.A.M., E.A.B., J.K., C.T.R.).ORCID 0000-0002-4712-3206
Jan SteffelDepartment of Cardiology, University of Zurich, Switzerland (J.S.).ORCID 0000-0002-1477-9153
Daniel WojdylaDuke Clinical Research Institute (A.P.C., H.H., M.R.P., J.H.A., K.H., R.D.L., J.P.P., D.W., C.B.G.), Duke University, Durham, NC.
Christopher B GrangerDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.ORCID 0000-0002-0045-3291
COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) InvestigatorsDivision of Cardiology (A.P.C., M.R.P., J.H.A., R.D.L., J.P.P., C.B.G.), Duke University, Durham, NC.
Duke University · USBrigham and Women's Hospital · USPopulation Health Research Institute · CAUppsala University · SEBern University of Applied Sciences · CHBoston University · USCenter for Clinical Research (United States) · USClinical Research Institute · USGoethe University Frankfurt · DEKyoto University · JPTaipei Veterans General Hospital · TWThrombolysis in Myocardial Infarction Study Group · USUniversity of Edinburgh · GBUniversity of Zurich · CH

Funding

Postdoctoral Training in Cardiovascular Clinical ResearchT32HL069749 · NHLBI · DUKE UNIVERSITY · PI MARK, DANIEL B · 2003 to 2023
$6.7M
NHLBI NIH HHS L30 HL149054NHLBI NIH HHS T32 HL069749
6 · The paper itself

Abstract

backgroundDirect oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation. Meta-analyses using individual patient data offer substantial advantages over study-level data.

methodsWe used individual patient data from the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database, which includes all patients randomized in the 4 pivotal trials of DOACs versus warfarin in atrial fibrillation (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]), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (HRs [95% CIs]) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex.

resultsA total of 71 683 patients were included (29 362 on standard-dose DOAC, 13 049 on lower-dose DOAC, and 29 272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke or systemic embolism (883/29 312 [3.01%] versus 1080/29 229 [3.69%]; HR, 0.81 [95% CI, 0.74-0.89]), death (2276/29 312 [7.76%] versus 2460/29 229 [8.42%]; HR, 0.92 [95% CI, 0.87-0.97]), and intracranial bleeding (184/29 270 [0.63%] versus 409/29 187 [1.40%]; HR, 0.45 [95% CI, 0.37-0.56]), but no statistically different hazard of major bleeding (1479/29 270 [5.05%] versus 1733/29 187 [5.94%]; HR, 0.86 [95% CI, 0.74-1.01]), whereas lower-dose DOACs were associated with no statistically different hazard of stroke or systemic embolism (531/13 049 [3.96%] versus 1080/29 229 [3.69%]; HR, 1.06 [95% CI, 0.95-1.19]) but a lower hazard of intracranial bleeding (55/12 985 [0.42%] versus 409/29 187 [1.40%]; HR, 0.28 [95% CI, 0.21-0.37]), death (1082/13 049 [8.29%] versus 2460/29 229 [8.42%]; HR, 0.90 [95% CI, 0.83-0.97]), and major bleeding (564/12 985 [4.34%] versus 1733/29 187 [5.94%]; HR, 0.63 [95% CI, 0.45-0.88]). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke or systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (

conclusionsCompared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with atrial fibrillation.

Indexed as

AnticoagulantsWarfarinAdministration, OralAgedAge FactorsFemaleHumansMaleRandomized Controlled Trials as TopicRisk FactorsSex FactorsAnticoagulantsWarfarinanticoagulantsatrial fibrillationmeta-analysisstrokewarfarin

Identifiers

PMID34985309
PMCPMC8800560
OpenAlexW4205709732

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.