Atrial Fibrillation, Cardiac Valve Disease, Venous Thromboses
Conditions
Keywords
Acenocoumarol, Cytochrome P450, Pharmacogenetics, Algorithm, CYP2C9, VKORC1, CYP4F2, P450 oxidoreductase (POR)
Brief summary
The use of coumarins has been a challenge for doctors because of its narrow therapeutic range and they show great inter and intra-individual variability in the dose necessary to achieve an international normalized ratio (INR) within the therapeutic range. Among the factors influencing the interindividual variability in the dose required include age, weight, Vitamin K in the diet, comorbidity as well as drug interactions and in recent years has also seen the importance of pharmacogenetic factors.
Detailed description
Demographic and clinical factors contribute approximately 20% to the total variability of dose requirements. In recent years it has highlighted the close relationship between the dose requirements of coumarin drugs and certain polymorphisms of genes involved in pharmacokinetics and pharmacodynamics of these drugs. The use of dosing algorithms that include pharmacogenetic information may help in the dose selection, improving efficacy and reducing adverse events. Studies have shown the relationship between genotype variants of CYP2C9 and VKORC1, CYP4F2 and apolipoprotein E (ApoE), which together with the demographic and clinical variants can explain between 50-60% of the variability in the response to these drugs.
Interventions
GENETICAcenocoumarol
A blood sample was collected for CYP2C9, VKORC1, CYP4F2, APOE and 2 variants of POR genotypes.
Sponsors
Instituto de Investigación Hospital Universitario La Paz
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Patients with Auricular fibrillation, venous thromboembolic disease and cardiac valve replacement receiving acenocoumarol. * Patients with stable dose of acenocoumarol (weekly dose variation of \<20% in the last 3 months). * Patients with an international normalised ratio within the range of 2 to 3 (in Auricular Fibrillation and venous thromboembolic disease) or 2.5 to 3.5 (in cardiac valve replacement) for at least the 3 previous consecutive months.
Exclusion criteria
* Patients with renal failure (calculated creatinine clearance ≤30 ml/min), hepatic disease (stage C of Child Plough Stage), thyroid dysfunction and/or cancer.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Creation of a pharmacogenetic algorithm of dosage for acenocoumarol | Up to 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Validation of the pharmacogenetic algorithm. | Up to 5 years |
Countries
Spain
Outcome results
None listed