ArticlePloS one2012
An acenocoumarol dosing algorithm using clinical and pharmacogenetic data in Spanish patients with thromboembolic disease.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals.Clinical pharmacology and therapeutics · 2019Pooled it
- Pharmacometabolomics applied to zonisamide pharmacokinetic parameter prediction.Metabolomics : Official journal of the Metabolomic Society · 2018Trial
- Trial
- PharmVar GeneFocus: CYP4F2.Clinical pharmacology and therapeutics · 2024Review
- Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial.Journal of clinical medicine · 2021Article
- A Pharmacogenetically Guided Acenocoumarol Dosing Algorithm for Chilean Patients: A Discovery Cohort Study.Frontiers in pharmacology · 2020Article
- Oral Anticoagulant Therapy-When Art Meets Science.Journal of clinical medicine · 2019Review
- Review
- Genetic and clinic predictors of new onset diabetes mellitus after transplantation.The pharmacogenomics journal · 2019Article
- Pharmacogenetic studies with oral anticoagulants. Genome-wide association studies in vitamin K antagonist and direct oral anticoagulants.Oncotarget · 2018Review
- Influence of genetic and non-genetic factors on acenocoumarol maintenance dose requirement in a Tunisian population.European journal of clinical pharmacology · 2018Article
- Clinical Implementation of Pharmacogenetic Testing in a Hospital of the Spanish National Health System: Strategy and Experience Over 3 Years.Clinical and translational science · 2018Article
- Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients.Pharmacogenomics and personalized medicine · 2018Article
- Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations.PloS one · 2016Article
- Article
- Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon.British journal of clinical pharmacology · 2014Review
- An acenocoumarol dose algorithm based on a South-Eastern European population.European journal of clinical pharmacology · 2013Observational
- Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
- Anticoagulation Management With Coumarinic Drugs in Chilean Patients.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
- Pharmacogenetics aspects of oral anticoagulants therapy.Journal of medicine and lifeArticle
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Appropriate dosing of coumarins is difficult to establish, due to significant inter-individual variability in the dose required to obtain stable anticoagulation. Several genetic and other clinical factors have been associated with the coumarins dose, and some pharmacogenetic-guided dosing algorithms for warfarin and acenocoumarol have been developed for mixed populations. We recruited 147 patients with thromboembolic disease who were on stable doses and with an international normalized ratio (INR) between 2 and 3. We ascertained the influence of clinical and genetic variables on the stable acenocoumarol dose by multiple linear regression analysis in a derivation cohort (DC; n = 117) and developed an algorithm for dosing that included clinical factors (age, body mass index and concomitant drugs) and genetic variations of VKORC1, CYP2C9, CYP4F2 and APOE. For purposes of comparison, a model including only clinical data was created. The clinical factors explained 22% of the dose variability, which increased to 60.6% when pharmacogenetic information was included (p<0.001); CYP4F2 and APOE variants explained 4.9% of this variability. The mean absolute error of the predicted acenocoumarol dose (mg/week) obtained with the pharmacogenetic algorithm was 3.63 vs. 5.08 mg/week with the clinical algorithm (95% CI: 0.88 to 2.04). In the testing cohort (n = 30), clinical factors explained a mere 7% of the dose variability, compared to 39% explained by the pharmacogenetic algorithm. Considering a more clinically relevant parameter, the pharmacogenetic algorithm correctly predicted the real stable dose in 59.8% of the cases (DC) vs. only 37.6% predicted by the clinical algorithm (95% CI: 10 to 35). Therefore the number of patients needed to genotype to avoid one over- or under-dosing was estimated to be 5.
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