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Age-stratified outcome of a genotype-guided dosing algorithm for acenocoumarol and phenprocoumon.
J Thromb Haemost. 2017 03; 15(3):454-464.JT

Abstract

Essentials The EU-PACT trial was used to investigate age on the interaction between coumarins and genotype. The results support the use of genotype-guided dosing for phenprocoumon in patients < 75 years. For patients ≥ 75 years the phenprocoumon algorithm should be revised and further tested. No influence of comorbidities and co-current drug use was found that could explain the differences.

SUMMARY

Background Age seemed to affect the interaction between coumarins and genotype in the acenocoumarol and phenprocoumon arm of the European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) trial. Objectives To investigate the effect of genotype-guided dosing stratified by age and the potential factors causing a difference. Patients/Methods Data from the acenocoumarol/phenprocoumon arm of the EU-PACT trial were used. The percentages of time below the therapeutic range, time above the therapeutic range and time in the therapeutic range (TTR) during the initial 12 weeks of therapy were compared between the genotype-guided group and the control group among younger (< 75 years) and older (≥ 75 years) patients by the use of independent t-tests, and adjusted for sex, height, weight and co-medications by the use of linear regression. Results Among younger phenprocoumon users, TTR during the first 12 weeks in the genotype-guided group (n = 55) was 9.5% (95% confidence interval [CI] 1.3 to 17.8) higher than in the control group (n = 63), with a remarkably lower percentage of time above this range (difference: - 9.6%, 95% CI - 19.0 to - 0.2) and a similar time below this range. Older patients dosed by the genotype-guided algorithm (n = 24) spent more time above the range (difference: 27.5%, 95% CI 12.9 to 42.0). For acenocoumarol users, there were no significant differences between the genotype-guided and control groups for most outcomes, except for a lower percentage of time below the range among older patients. Conclusions The genotype-guided algorithm for phenprocoumon in the EU-PACT trial benefitted younger patients more, but for older patients the algorithm needs to be revised and tested in further research.

Authors+Show Affiliations

Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.Department of Applied Health Research, University College London, London, UK.Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.Clinical Pharmacology Unit, Academic General Hospital of Evros, Alexandroupolis, Greece. Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.No affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27992949

Citation

Zhang, Y, et al. "Age-stratified Outcome of a Genotype-guided Dosing Algorithm for Acenocoumarol and Phenprocoumon." Journal of Thrombosis and Haemostasis : JTH, vol. 15, no. 3, 2017, pp. 454-464.
Zhang Y, de Boer A, Verhoef TI, et al. Age-stratified outcome of a genotype-guided dosing algorithm for acenocoumarol and phenprocoumon. J Thromb Haemost. 2017;15(3):454-464.
Zhang, Y., de Boer, A., Verhoef, T. I., van der Meer, F. J., Le Cessie, S., Manolopoulos, V. G., & Maitland-van der Zee, A. H. (2017). Age-stratified outcome of a genotype-guided dosing algorithm for acenocoumarol and phenprocoumon. Journal of Thrombosis and Haemostasis : JTH, 15(3), 454-464. https://doi.org/10.1111/jth.13601
Zhang Y, et al. Age-stratified Outcome of a Genotype-guided Dosing Algorithm for Acenocoumarol and Phenprocoumon. J Thromb Haemost. 2017;15(3):454-464. PubMed PMID: 27992949.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-stratified outcome of a genotype-guided dosing algorithm for acenocoumarol and phenprocoumon. AU - Zhang,Y, AU - de Boer,A, AU - Verhoef,T I, AU - van der Meer,F J M, AU - Le Cessie,S, AU - Manolopoulos,V G, AU - Maitland-van der Zee,A H, AU - ,, Y1 - 2017/02/17/ PY - 2016/05/28/received PY - 2016/12/20/pubmed PY - 2018/2/2/medline PY - 2016/12/20/entrez KW - age groups KW - algorithms KW - coumarins KW - cytochrome P450 2C9 KW - pharmacogenetics KW - vitamin K epoxide reductases SP - 454 EP - 464 JF - Journal of thrombosis and haemostasis : JTH JO - J. Thromb. Haemost. VL - 15 IS - 3 N2 - : Essentials The EU-PACT trial was used to investigate age on the interaction between coumarins and genotype. The results support the use of genotype-guided dosing for phenprocoumon in patients < 75 years. For patients ≥ 75 years the phenprocoumon algorithm should be revised and further tested. No influence of comorbidities and co-current drug use was found that could explain the differences. SUMMARY: Background Age seemed to affect the interaction between coumarins and genotype in the acenocoumarol and phenprocoumon arm of the European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) trial. Objectives To investigate the effect of genotype-guided dosing stratified by age and the potential factors causing a difference. Patients/Methods Data from the acenocoumarol/phenprocoumon arm of the EU-PACT trial were used. The percentages of time below the therapeutic range, time above the therapeutic range and time in the therapeutic range (TTR) during the initial 12 weeks of therapy were compared between the genotype-guided group and the control group among younger (< 75 years) and older (≥ 75 years) patients by the use of independent t-tests, and adjusted for sex, height, weight and co-medications by the use of linear regression. Results Among younger phenprocoumon users, TTR during the first 12 weeks in the genotype-guided group (n = 55) was 9.5% (95% confidence interval [CI] 1.3 to 17.8) higher than in the control group (n = 63), with a remarkably lower percentage of time above this range (difference: - 9.6%, 95% CI - 19.0 to - 0.2) and a similar time below this range. Older patients dosed by the genotype-guided algorithm (n = 24) spent more time above the range (difference: 27.5%, 95% CI 12.9 to 42.0). For acenocoumarol users, there were no significant differences between the genotype-guided and control groups for most outcomes, except for a lower percentage of time below the range among older patients. Conclusions The genotype-guided algorithm for phenprocoumon in the EU-PACT trial benefitted younger patients more, but for older patients the algorithm needs to be revised and tested in further research. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/27992949/Age_stratified_outcome_of_a_genotype_guided_dosing_algorithm_for_acenocoumarol_and_phenprocoumon_ L2 - https://doi.org/10.1111/jth.13601 DB - PRIME DP - Unbound Medicine ER -