A novel acenocoumarol pharmacogenomic dosing algorithm for the Greek population of EU-PACT trial

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 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-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