Evidence map›Paper›PMID 24251360›Full record

Trial reportThe New England journal of medicine2013

A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.

Talitha I Verhoef, Georgia Ragia, Anthonius de Boer, Rita Barallon, Genovefa Kolovou, Vana Kolovou, Stavros Konstantinides, Saskia Le Cessie, Efstratios Maltezos, Felix J M van der Meer and 10 more

2 registry-linked trialsOpen access · greenAbstract readComparative 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 2 registered trials, which are not on this map. Cited by 87 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 6 pooled it
23.0field-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.

NCT01119261 phase4completednot on this map

EUropean Pharmacogenetics of AntiCoagulant Therapy - Acenocoumarol

TypeinterventionalSponsorUtrecht Institute for Pharmaceutical SciencesRan2010 to 2013Enrolled970ConditionsVenous Thromboembolism, Atrial FibrillationArmsGenotype-guided dosing algorithm, Non-genotype-guided dosing algorithm
NCT01119274 phase4completednot on this map

EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon

TypeinterventionalSponsorUtrecht Institute for Pharmaceutical SciencesRan2010 to 2013Enrolled970ConditionsVenous Thromboembolism (VTE), Atrial Fibrillation (AF)ArmsGenotype-guided dosing algorithm, Non-genotype-guided dosing algorithm
3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 6 syntheses or guidelines pooled it, 226 citations in OpenAlex.

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  19. Drug metabolism and drug transport of the 100 most prescribed oral drugs.Basic & clinical pharmacology & toxicology · 2022
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27 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 at 8 institutions in 4 countries.

Talitha I VerhoefThe authors' affiliations are listed in the Appendix.
Georgia Ragia
Anthonius de Boer
Rita Barallon
Genovefa Kolovou
Vana Kolovou
Stavros Konstantinides
Saskia Le Cessie
Efstratios Maltezos
Felix J M van der Meer
William K Redekop
Mary Remkes
Frits R Rosendaal
Rianne M F van Schie
Anna Tavridou
Dimitrios Tziakas
Mia Wadelius
Vangelis G Manolopoulos
Anke H Maitland-van der Zee
EU-PACT Group
Onassis Cardiac Surgery Center · GRPharmo Institute · NLUniversity Hospital of Alexandroupolis · GRUtrecht University · NLDemocritus University of Thrace · GRLaboratory of Molecular Genetics · PLLeiden University Medical Center · NLUppsala University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundObservational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy.

methodsWe conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks.

resultsA total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P=0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P=0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events.

conclusionsGenotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. (Funded by the European Commission Seventh Framework Programme and others; EU-PACT ClinicalTrials.gov numbers, NCT01119261 and NCT01119274.).

Indexed as

AlgorithmsGenotypeAcenocoumarolAgedAnticoagulantsAryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2C9FemaleFollow-Up StudiesHumansInternational Normalized RatioMaleMiddle AgedPharmacogeneticsPhenprocoumonSingle-Blind MethodAcenocoumarolAnticoagulantsAryl Hydrocarbon HydroxylasesCYP2C9 protein, humanCytochrome P-450 CYP2C9PhenprocoumonVitamin K Epoxide ReductasesVKORC1 protein, human

Identifiers

PMID24251360
OpenAlexW1976568296

What OpenQuestion holds

Textmetadata
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.