Georgia Ragia1, Vana Kolovou2, Genovefa Kolovou2, Stavros Konstantinides3, Efstratios Maltezos4, Anna Tavridou5,6, Dimitrios Tziakas3, Anke H Maitland-van der Zee7, Vangelis G Manolopoulos5,6. 1. DNALEX S.A., Leontaridou 2, Alexandroupolis, Greece. 2. Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece. 3. University Cardiology Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. 4. Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. 5. Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. 6. Clinical Pharmacology Unit, Academic General Hospital of Evros, Alexandroupolis, Greece. 7. Division of Pharmacoepidemiology & Clinical Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Abstract
AIM: To generate and validate a pharmacogenomic-guided (PG) dosing algorithm for acenocoumarol in the Greek population. To compare its performance with other PG algorithms developed for the Greek population. PATIENTS & METHODS: A total of 140 Greek patients participants of the EU-PACT trial foracenocoumarol, a randomized clinical trial that prospectively compared the effect of a PG dosing algorithm with a clinical dosing algorithm on the percentage of time within INR therapeutic range, who reached acenocoumarol stable dose were included in the study. RESULTS: CYP2C9 and VKORC1 genotypes, age and weight affected acenocoumarol dose and predicted 53.9% of its variability. EU-PACT PG algorithm overestimated acenocoumarol dose across all different CYP2C9/VKORC1 functional phenotype bins (predicted dose vs stable dose in normal responders 2.31 vs 2.00 mg/day, p = 0.028, in sensitive responders 1.72 vs 1.50 mg/day, p = 0.003, in highly sensitive responders 1.39 vs 1.00 mg/day, p = 0.029). The PG algorithm previously developed for the Greek population overestimated the dose in normal responders (2.51 vs 2.00 mg/day, p < 0.001). CONCLUSION: Ethnic-specific dosing algorithm is suggested for better prediction of acenocoumarol dosage requirements in patients of Greek origin.
RCT Entities:
AIM: To generate and validate a pharmacogenomic-guided (PG) dosing algorithm for acenocoumarol in the Greek population. To compare its performance with other PG algorithms developed for the Greek population. PATIENTS & METHODS: A total of 140 Greek patientsparticipants of the EU-PACT trial for acenocoumarol, a randomized clinical trial that prospectively compared the effect of a PG dosing algorithm with a clinical dosing algorithm on the percentage of time within INR therapeutic range, who reached acenocoumarol stable dose were included in the study. RESULTS:CYP2C9 and VKORC1 genotypes, age and weight affected acenocoumarol dose and predicted 53.9% of its variability. EU-PACTPG algorithm overestimated acenocoumarol dose across all different CYP2C9/VKORC1 functional phenotype bins (predicted dose vs stable dose in normal responders 2.31 vs 2.00 mg/day, p = 0.028, in sensitive responders 1.72 vs 1.50 mg/day, p = 0.003, in highly sensitive responders 1.39 vs 1.00 mg/day, p = 0.029). The PG algorithm previously developed for the Greek population overestimated the dose in normal responders (2.51 vs 2.00 mg/day, p < 0.001). CONCLUSION: Ethnic-specific dosing algorithm is suggested for better prediction of acenocoumarol dosage requirements in patients of Greek origin.