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A new pharmacogenetic algorithm to predict the most appropriate dosage of acenocoumarol for stable anticoagulation in a mixed Spanish population
- Source :
- Biblos-e Archivo. Repositorio Institucional de la UAM, instname, PLoS ONE, Vol 11, Iss 3, p e0150456 (2016), PLoS ONE, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid
- Publication Year :
- 2016
- Publisher :
- Public Library of Science, 2016.
-
Abstract
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.There is a strong association between genetic polymorphisms and the acenocoumarol dosage requirements. Genotyping the polymorphisms involved in the pharmacokinetics and pharmacodynamics of acenocoumarol before starting anticoagulant therapy would result in a better quality of life and a more efficient use of healthcare resources. The objective of this study is to develop a new algorithm that includes clinical and genetic variables to predict the most appropriate acenocoumarol dosage for stable anticoagulation in a wide range of patients. We recruited 685 patients from 2 Spanish hospitals and 1 primary healthcare center. We randomly chose 80% of the patients (n = 556), considering an equitable distribution of genotypes to form the generation cohort. The remaining 20% (n = 129) formed the validation cohort. Multiple linear regression was used to generate the algorithm using the acenocoumarol stable dosage as the dependent variable and the clinical and genotypic variables as the independent variables. The variables included in the algorithm were age, weight, amiodarone use, enzyme inducer status, international normalized ratio target range and the presence of CYP2C9∗2 (rs1799853), CYP2C9∗3 (rs1057910), VKORC1 (rs9923231) and CYP4F2 (rs2108622). The coefficient of determination (R2) explained by the algorithm was 52.8% in the generation cohort and 64% in the validation cohort. The following R2 values were evaluated by pathology: atrial fibrillation, 57.4%; valve replacement, 56.3%; and venous thromboembolic disease, 51.5%. When the patients were classified into 3 dosage groups according to the stable dosage (21 mg/week), the percentage of correctly classified patients was higher in the intermediate group, whereas differences between pharmacogenetic and clinical algorithms increased in the extreme dosage groups. Our algorithm could improve acenocoumarol dosage selection for patients who will begin treatment with this drug, especially in extreme-dosage patients. The predictability of the pharmacogenetic algorithm did not vary significantly between diseases.<br />This study was funded by a grant from the Spanish Ministry of Health and Social Policy (Instituto de Salud Carlos III, PI07/0710) and the Andalusian Regional Ministry of Health (Progress and Health Foundation, PI-0717-2013)
- Subjects :
- 0301 basic medicine
Male
Heredity
CYP4F2
España
lcsh:Medicine
Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings]
030204 cardiovascular system & hematology
Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Benzopyrans::Coumarins::4-Hydroxycoumarins::Acenocoumarol [Medical Subject Headings]
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
0302 clinical medicine
Quality of life
Coumarins
Atrial Fibrillation
Medicine and Health Sciences
Medicine
lcsh:Science
Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings]
Acenocoumarol
Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Hematologic Agents::Anticoagulants [Medical Subject Headings]
Multidisciplinary
Algoritmos
Pharmaceutics
Applied Mathematics
Simulation and Modeling
Pharmacogenetic
Farmacogenética
Middle Aged
Farmacia
Humanos
Chemistry
Genetic Mapping
Cohort
Physical Sciences
Female
VKORC1
Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Pharmacology::Pharmacogenetics [Medical Subject Headings]
Algorithm
Arrhythmia
Algorithms
medicine.drug
Research Article
Phenomena and Processes::Mathematical Concepts::Algorithms [Medical Subject Headings]
Medicina
Cardiology
Check Tags::Male [Medical Subject Headings]
Variant Genotypes
Research and Analysis Methods
03 medical and health sciences
Dose Prediction Methods
Linear regression
Genetics
A new algorithm
Humans
Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings]
Acenocoumarol dosage
CYP2C9
Aged
Pharmacology
Clinical Genetics
business.industry
lcsh:R
Chemical Compounds
Biology and Life Sciences
Anticoagulants
Human Genetics
Appropriate acenocoumarol dosag
Stable anticoagulation
Acenocumarol
Anticoagulantes
030104 developmental biology
Check Tags::Female [Medical Subject Headings]
Pharmacogenetics
Spain
lcsh:Q
business
Mathematics
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Biblos-e Archivo. Repositorio Institucional de la UAM, instname, PLoS ONE, Vol 11, Iss 3, p e0150456 (2016), PLoS ONE, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid
- Accession number :
- edsair.doi.dedup.....3fa1be8e9dcefd79189a05363d54e879