Age-stratified outcome of genotype-guided dosing algorithm for acenocoumarol and phenprocoumon

Abstract

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 was used. The percentage of time below, above and 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 using independent t-test and adjust for sex, height, weight and co-medications using 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 the control group (n=63) with a remarkable lower percentage of time above this range (difference: -9.6%, 95%CI: -19.0 to -0.2) and similar time below this range. Older patients dosed by the genotype-guided algorithm (n=24) spend 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 group for most outcomes, except for a lower percentage of time below range among older patients. CONCLUSIONS: The genotype-guided algorithm for phenprocoumon in the EU-PACT trial benefitted younger patients more, while for older patients, the algorithm need to be revised and tested in further research. This article is protected by copyright. All rights reserved.