Evidence map›Paper›PMID 24251361›Full record

Trial reportThe New England journal of medicine2013

A pharmacogenetic versus a clinical algorithm for warfarin dosing.

Stephen E Kimmel, Benjamin French, Scott E Kasner, Julie A Johnson, Jeffrey L Anderson, Brian F Gage, Yves D Rosenberg, Charles S Eby, Rosemary A Madigan, Robert B McBane and 22 more

3 registry-linked trialsAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 327 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
327citing papers in PubMed, 15 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.

NCT00839657 phase3completednot on this map

A Randomized, Multi-Center, Double-Blind Clinical Trial to Evaluate the Use of Clinical Plus Genetic Information to Guide Warfarin Therapy Initiation and Improve Anticoagulation Control for Patients

TypeinterventionalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran2009 to 2013Enrolled1,015ConditionsStroke, Venous Thrombosis, Atrial Fibrillation, Atrial FlutterArmsGenotype-guided dosing algorithm for warfarin, Clinical-guided dosing algorithm for warfarin
NCT03797534 naunknown statusnot on this mapstarted 2019, after this paper: background citation

Individualized Administration of Warfarin by Polymorphisms of VKORC1 and CYP2C9 Genes:A Randomized Controlled Trial, Multi-center Trial

TypeinterventionalSponsorFujian Medical UniversityRan2019 to 2023Enrolled600ConditionsHeart Valve ProsthesisArmsdose regime
NCT03894878 completednot on this mapstarted 2019, after this paper: background citation

Association Between Risk Scores for Genetic Variants and Percentage of Time in Therapeutic Range for Participants With Atrial Fibrillation, Deep Vein Thrombosis, and/or Intracardiac Thrombosis Taking Warfarin

TypeobservationalSponsorCipherome, Inc.Ran2019 to 2022Enrolled200ConditionsAtrial Fibrillation, Deep Vein Thrombosis, Intracardiac Thrombus, Pulmonary Embolism
3 · Its place in the literature

Who cites it

327 citing papers in PubMed, 15 syntheses or guidelines pooled it.

  1. Pooled it
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  4. Warfarin dosing algorithms: A systematic review.British journal of clinical pharmacology · 2021
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  5. Guideline
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  7. Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases.Genetics in medicine : official journal of the American College of Medical Genetics · 2020
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  14. Guideline
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  16. Trial
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267 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors.

Stephen E KimmelThe authors' affiliations are listed in the Appendix.
Benjamin French
Scott E Kasner
Julie A Johnson
Jeffrey L Anderson
Brian F Gage
Yves D Rosenberg
Charles S Eby
Rosemary A Madigan
Robert B McBane
Sherif Z Abdel-Rahman
Scott M Stevens
Steven Yale
Emile R Mohler
Margaret C Fang
Vinay Shah
Richard B Horenstein
Nita A Limdi
James A S Muldowney
Jaspal Gujral
Patrice Delafontaine
Robert J Desnick
Thomas L Ortel
Henny H Billett
Robert C Pendleton
Nancy L Geller
Jonathan L Halperin
Samuel Z Goldhaber
Michael D Caldwell
Robert M Califf
Jonas H Ellenberg
COAG Investigators

Funding

Predictors of hemorrhage among patients on direct acting oral anticoagulantsR01HL092173 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LIMDI, NITA A · 2008 to 2023
$10.4M
NHLBI NIH HHS HHSN268200800003CNHLBI NIH HHS R01 HL092173PHS HHS HHSN-268200800003C
6 · The paper itself

Abstract

backgroundThe clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.

methodsWe randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy.

resultsAt 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.

conclusionsGenotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).

Indexed as

AlgorithmsGenotypeAdultAgedAnticoagulantsAryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2C9Double-Blind MethodFemaleFollow-Up StudiesHemorrhageHumansInternational Normalized RatioMalePharmacogeneticsThromboembolismAnticoagulantsAryl Hydrocarbon HydroxylasesCYP2C9 protein, humanCytochrome P-450 CYP2C9Vitamin K Epoxide ReductasesVKORC1 protein, humanWarfarin

Identifiers

PMID24251361
PMCPMC3942158

What OpenQuestion holds

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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.