Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users

T I Verhoef; W K Redekop; M M Buikema; T Schalekamp; F J M Van Der Meer; S Le Cessie; J A M Wessels; R M F Van Schie; A De Boer; M Teichert; L E Visser; A H Maitland-Van Der Zee; EU-PACT Group

doi:10.1111/j.1538-7836.2012.04633.x

Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users

T I Verhoef, W K Redekop, M M Buikema, T Schalekamp, F J M Van Der Meer, S Le Cessie, J A M Wessels, R M F Van Schie, A De Boer, M Teichert, L E Visser, A H Maitland-Van Der Zee, EU-PACT Group

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration of the effects of these genes on anticoagulation is not yet known.

OBJECTIVES: In the present study, the effects of these polymorphisms on the risk of underanticoagulation and overanticoagulation over time after the start of acenocoumarol were investigated.

PATIENTS/METHODS: In three cohorts, we analyzed the relationship between the CYP2C9 and VKORC1 genotypes and the incidence of subtherapeutic or supratherapeutic International Normalized Ratio (INR) values (< 2 and > 3.5) or severe overanticoagulation (INR > 6) for different time periods after treatment initiation.

RESULTS: Patients with polymorphisms in CYP2C9 and VKORC1 had a higher risk of overanticoagulation (up to 74%) and a lower risk of underanticoagulation (down to 45%) in the first month of treatment with acenocoumarol, but this effect diminished after 1-6 months.

CONCLUSIONS: Knowledge of the patient's genotype therefore might assist physicians to adjust doses in the first month(s) of therapy.

Original language	English
Pages (from-to)	606-614
Number of pages	9
Journal	Journal of Thrombosis and Haemostasis
Volume	10
Issue number	4
DOIs	https://doi.org/10.1111/j.1538-7836.2012.04633.x
Publication status	Published - Apr 2012

Bibliographical note

Keywords

Acenocoumarol
Aged
Anticoagulants
Aryl Hydrocarbon Hydroxylases
Blood Coagulation
Cytochrome P-450 CYP2C9
Drug Administration Schedule
Drug Dosage Calculations
Drug Monitoring
Female
Gene Frequency
Genotype
Humans
International Normalized Ratio
Male
Medication Errors
Mixed Function Oxygenases
Netherlands
Pharmacogenetics
Phenotype
Polymorphism, Genetic
Predictive Value of Tests
Risk Assessment
Risk Factors
Time Factors
Vitamin K Epoxide Reductases

Access to Document

10.1111/j.1538-7836.2012.04633.x

Cite this

Verhoef, T. I., Redekop, W. K., Buikema, M. M., Schalekamp, T., Van Der Meer, F. J. M., Le Cessie, S., Wessels, J. A. M., Van Schie, R. M. F., De Boer, A., Teichert, M., Visser, L. E., Maitland-Van Der Zee, A. H., & EU-PACT Group (2012). Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users. Journal of Thrombosis and Haemostasis, 10(4), 606-614. https://doi.org/10.1111/j.1538-7836.2012.04633.x

@article{16ad52c632694e34af692d2ed118baf1,

title = "Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users",

abstract = "BACKGROUND: The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration of the effects of these genes on anticoagulation is not yet known.OBJECTIVES: In the present study, the effects of these polymorphisms on the risk of underanticoagulation and overanticoagulation over time after the start of acenocoumarol were investigated.PATIENTS/METHODS: In three cohorts, we analyzed the relationship between the CYP2C9 and VKORC1 genotypes and the incidence of subtherapeutic or supratherapeutic International Normalized Ratio (INR) values (< 2 and > 3.5) or severe overanticoagulation (INR > 6) for different time periods after treatment initiation.RESULTS: Patients with polymorphisms in CYP2C9 and VKORC1 had a higher risk of overanticoagulation (up to 74%) and a lower risk of underanticoagulation (down to 45%) in the first month of treatment with acenocoumarol, but this effect diminished after 1-6 months.CONCLUSIONS: Knowledge of the patient's genotype therefore might assist physicians to adjust doses in the first month(s) of therapy.",

keywords = "Acenocoumarol, Aged, Anticoagulants, Aryl Hydrocarbon Hydroxylases, Blood Coagulation, Cytochrome P-450 CYP2C9, Drug Administration Schedule, Drug Dosage Calculations, Drug Monitoring, Female, Gene Frequency, Genotype, Humans, International Normalized Ratio, Male, Medication Errors, Mixed Function Oxygenases, Netherlands, Pharmacogenetics, Phenotype, Polymorphism, Genetic, Predictive Value of Tests, Risk Assessment, Risk Factors, Time Factors, Vitamin K Epoxide Reductases",

author = "Verhoef, {T I} and Redekop, {W K} and Buikema, {M M} and T Schalekamp and {Van Der Meer}, {F J M} and {Le Cessie}, S and Wessels, {J A M} and {Van Schie}, {R M F} and {De Boer}, A and M Teichert and Visser, {L E} and {Maitland-Van Der Zee}, {A H} and {EU-PACT Group}",

note = "{\textcopyright} 2012 International Society on Thrombosis and Haemostasis.",

year = "2012",

month = apr,

doi = "10.1111/j.1538-7836.2012.04633.x",

language = "English",

volume = "10",

pages = "606--614",

journal = "Journal of Thrombosis and Haemostasis",

issn = "1538-7933",

publisher = "Elsevier BV",

number = "4",

}

Verhoef, TI, Redekop, WK, Buikema, MM, Schalekamp, T, Van Der Meer, FJM, Le Cessie, S, Wessels, JAM, Van Schie, RMF, De Boer, A, Teichert, M, Visser, LE, Maitland-Van Der Zee, AH & EU-PACT Group 2012, 'Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users', Journal of Thrombosis and Haemostasis, vol. 10, no. 4, pp. 606-614. https://doi.org/10.1111/j.1538-7836.2012.04633.x

TY - JOUR

T1 - Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users

AU - Verhoef, T I

AU - Redekop, W K

AU - Buikema, M M

AU - Schalekamp, T

AU - Van Der Meer, F J M

AU - Le Cessie, S

AU - Wessels, J A M

AU - Van Schie, R M F

AU - De Boer, A

AU - Teichert, M

AU - Visser, L E

AU - Maitland-Van Der Zee, A H

AU - EU-PACT Group

PY - 2012/4

Y1 - 2012/4

N2 - BACKGROUND: The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration of the effects of these genes on anticoagulation is not yet known.OBJECTIVES: In the present study, the effects of these polymorphisms on the risk of underanticoagulation and overanticoagulation over time after the start of acenocoumarol were investigated.PATIENTS/METHODS: In three cohorts, we analyzed the relationship between the CYP2C9 and VKORC1 genotypes and the incidence of subtherapeutic or supratherapeutic International Normalized Ratio (INR) values (< 2 and > 3.5) or severe overanticoagulation (INR > 6) for different time periods after treatment initiation.RESULTS: Patients with polymorphisms in CYP2C9 and VKORC1 had a higher risk of overanticoagulation (up to 74%) and a lower risk of underanticoagulation (down to 45%) in the first month of treatment with acenocoumarol, but this effect diminished after 1-6 months.CONCLUSIONS: Knowledge of the patient's genotype therefore might assist physicians to adjust doses in the first month(s) of therapy.

AB - BACKGROUND: The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration of the effects of these genes on anticoagulation is not yet known.OBJECTIVES: In the present study, the effects of these polymorphisms on the risk of underanticoagulation and overanticoagulation over time after the start of acenocoumarol were investigated.PATIENTS/METHODS: In three cohorts, we analyzed the relationship between the CYP2C9 and VKORC1 genotypes and the incidence of subtherapeutic or supratherapeutic International Normalized Ratio (INR) values (< 2 and > 3.5) or severe overanticoagulation (INR > 6) for different time periods after treatment initiation.RESULTS: Patients with polymorphisms in CYP2C9 and VKORC1 had a higher risk of overanticoagulation (up to 74%) and a lower risk of underanticoagulation (down to 45%) in the first month of treatment with acenocoumarol, but this effect diminished after 1-6 months.CONCLUSIONS: Knowledge of the patient's genotype therefore might assist physicians to adjust doses in the first month(s) of therapy.

KW - Acenocoumarol

KW - Aged

KW - Anticoagulants

KW - Aryl Hydrocarbon Hydroxylases

KW - Blood Coagulation

KW - Cytochrome P-450 CYP2C9

KW - Drug Administration Schedule

KW - Drug Dosage Calculations

KW - Drug Monitoring

KW - Female

KW - Gene Frequency

KW - Genotype

KW - Humans

KW - International Normalized Ratio

KW - Male

KW - Medication Errors

KW - Mixed Function Oxygenases

KW - Netherlands

KW - Pharmacogenetics

KW - Phenotype

KW - Polymorphism, Genetic

KW - Predictive Value of Tests

KW - Risk Assessment

KW - Risk Factors

KW - Time Factors

KW - Vitamin K Epoxide Reductases

U2 - 10.1111/j.1538-7836.2012.04633.x

DO - 10.1111/j.1538-7836.2012.04633.x

M3 - Article

C2 - 22252093

SN - 1538-7933

VL - 10

SP - 606

EP - 614

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

IS - 4

ER -

Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this