Trial reportJournal of thrombosis and haemostasis : JTH2010
Ability of VKORC1 and CYP2C9 to predict therapeutic warfarin dose during the initial weeks of therapy.
Trial report in Journal of thrombosis and haemostasis : JTH, 2010. 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 30 papers, 4 of them syntheses that pooled 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.
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.
Genetics Informatics Trial (GIFT) of Warfarin to Prevent Deep Venous Thrombosis (DVT)
Quantitative Pharmacogenomics of the Anticoagulant Response to Warfarin in Healthy Subjects
Who cites it
30 citing papers in PubMed, 4 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update.Clinical pharmacology and therapeutics · 2017Guideline
- Limited clinical utility of genotype-guided warfarin initiation dosing algorithms versus standard therapy: a meta-analysis and trial sequential analysis of 11 randomized controlled trials.The pharmacogenomics journal · 2015Pooled it
- Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin.Chest · 2015Pooled it
- Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing.Clinical pharmacology and therapeutics · 2011Guideline
- CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation.European journal of clinical pharmacology · 2013Trial
- Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters.European journal of clinical pharmacology · 2011Trial
- Article
- Determining Drug Exposure Based on Medication Dispensing Data: A Validation Study of Vitamin K Antagonist Treatment Episodes Against INR Records.Pharmacoepidemiology and drug safety · 2025Article
- Prevalence of risk phenotypes associated withFrontiers in pharmacology · 2025Article
- New insights into the role of VKORC1 polymorphisms for optimal warfarin dose selection in Caribbean Hispanic patients through an external validation of a population PK/PD model.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Reduced dose direct oral anticoagulants compared with warfarin with high time in therapeutic range in nonvalvular atrial fibrillation.Journal of thrombosis and thrombolysis · 2023Article
- Opposite Response to Vitamin K Antagonists: A Report of Two Cases and Systematic Review of Literature.Journal of personalized medicine · 2022Review
- Warfarin Dosing in Patients With CYP2C9*5 Variant Alleles.Clinical pharmacology and therapeutics · 2022Article
- A pharmacogenetic pilot study ofJournal of diabetes and metabolic disorders · 2021Article
- Oral Anticoagulant Therapy-When Art Meets Science.Journal of clinical medicine · 2019Review
- The impact of R353Q genetic polymorphism in coagulation factor VII on the initial anticoagulant effect exerted by warfarin.European journal of clinical pharmacology · 2019Article
- The Influence of CYP2C9 and VKORC1 Gene Polymorphisms on the Response to Warfarin in Egyptians.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2018Article
- Quality of anticoagulation control and hemorrhage risk among African American and European American warfarin users.Pharmacogenetics and genomics · 2017Article
- Genotype and risk of major bleeding during warfarin treatment.Pharmacogenomics · 2014Article
- Electronic health record design and implementation for pharmacogenomics: a local perspective.Genetics in medicine : official journal of the American College of Medical Genetics · 2013Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundCYP2C9 and VKORC1 genotypes predict therapeutic warfarin dose at initiation of therapy; however, the predictive ability of genetic information after a week or longer is unknown. Experts have hypothesized that genotype becomes irrelevant once international normalized ratio (INR) values are available because INR response reflects warfarin sensitivity.
methodsWe genotyped the participants in the Prevention of Recurrent Venous Thromboembolism (PREVENT) trial, who had idiopathic venous thromboemboli and began low-intensity warfarin (therapeutic INR 1.5-2.0) using a standard dosing protocol. To develop pharmacogenetic models, we quantified the effect of genotypes, clinical factors, previous doses and INR on therapeutic warfarin dose in the 223 PREVENT participants who were randomized to warfarin and achieved stable therapeutic INRs.
resultsA pharmacogenetic model using data from day 0 (before therapy initiation) explained 54% of the variability in therapeutic dose (R(2)). The R(2) increased to 68% at day 7, 75% at day 14, and 77% at day 21, because of increasing contributions from prior doses and INR response. Although CYP2C9 and VKORC1 genotypes were significant independent predictors of therapeutic dose at each weekly interval, the magnitude of their predictive ability diminished over time: partial R(2) of genotype was 43% at day 0, 12% at day 7, 4% at day 14, and 1% at day 21.
conclusionOver the first weeks of warfarin therapy, INR and prior dose become increasingly predictive of therapeutic dose, and genotype becomes less relevant. However, at day 7, genotype remains clinically relevant, accounting for 12% of therapeutic dose variability.
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Identifiers
What OpenQuestion holds
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.