Evidence map›Paper›PMID 24251363›Full record

Trial reportThe New England journal of medicine2013

A randomized trial of genotype-guided dosing of warfarin.

Munir Pirmohamed, Girvan Burnside, Niclas Eriksson, Andrea L Jorgensen, Cheng Hock Toh, Toby Nicholson, Patrick Kesteven, Christina Christersson, Bengt Wahlström, Christina Stafberg and 10 more

4 registry-linked trialsAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed 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 4 registered trials, which are not on this map. Cited by 348 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
348citing papers in PubMed, 13 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.

NCT01119300 phase4completednot on this map

EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin

TypeinterventionalSponsorUtrecht Institute for Pharmaceutical SciencesRan2011 to 2013Enrolled455ConditionsVenous Thromboembolism, Atrial FibrillationArmsGenotype-guided dosing algorithm, Standard care
NCT03512080 completednot on this mapstarted 2018, after this paper: background citation

National Institute of Health Research (NIHR) Global Health Research Group on Warfarin Anticoagulation in Patients with Cardiovascular Disease in Sub-Saharan Africa

Typeobservational_patient_registrySponsorUniversity of LiverpoolRan2018 to 2024Enrolled681ConditionsCardiovascular Diseases
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

348 citing papers in PubMed, 13 syntheses or guidelines pooled it.

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  4. Warfarin dosing algorithms: A systematic review.British journal of clinical pharmacology · 2021
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  5. 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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  13. Guideline
  14. Trial
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288 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Munir PirmohamedFrom the University of Liverpool (M.P., G.B., A.L.J., C.H.T., J.E.Z., P.R.W.) and Royal Liverpool and Broadgreen University Hospital National Health Service (NHS) Trust (M.P., C.H.T.), Liverpool, Whiston Hospital, Prescot (T.N.), and Newcastle upon Tyne NHS Trust (P.K.) and Newcastle University (J.B.L., A.K.D., P.A., F.K.), Newcastle upon Tyne - all in the United Kingdom; Uppsala University, Department of Medical Sciences (N.E., C.C., H.K., M.W.), Uppsala Clinical Research Center (N.E.) and Uppsala University Hospital (C.C., B.W., M.W.), Uppsala, and Enköping Hospital, Enköping (C.S.) - all in Sweden; and Utrecht University, Utrecht, the Netherlands (A.H.M.Z.).
Girvan Burnside
Niclas Eriksson
Andrea L Jorgensen
Cheng Hock Toh
Toby Nicholson
Patrick Kesteven
Christina Christersson
Bengt Wahlström
Christina Stafberg
J Eunice Zhang
Julian B Leathart
Hugo Kohnke
Anke H Maitland-van der Zee
Paula R Williamson
Ann K Daly
Peter Avery
Farhad Kamali
Mia Wadelius
EU-PACT Group

Funding

Department of HealthMedical Research Council G0400488
6 · The paper itself

Abstract

backgroundThe level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy.

methodsWe conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G→A) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation.

resultsA total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001).

conclusionsPharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy. (Funded by the European Commission Seventh Framework Programme and others; ClinicalTrials.gov number, NCT01119300.).

Indexed as

GenotypeAdultAgedAged, 80 and overAnticoagulantsAryl Hydrocarbon HydroxylasesAtrial FibrillationCytochrome P-450 CYP2C9FemaleHemorrhageHumansInternational Normalized RatioKaplan-Meier EstimateMaleMiddle AgedPharmacogeneticsAnticoagulantsAryl Hydrocarbon HydroxylasesCYP2C9 protein, humanCytochrome P-450 CYP2C9Vitamin K Epoxide ReductasesVKORC1 protein, humanWarfarin

Identifiers

PMID24251363

What OpenQuestion holds

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Read underepoch 390

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.