A Novel Acenocoumarol Pharmacogenomic Dosing Algorithm for the Greek Population of EU-PACT Trial

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 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.

Keywords::

• acenocoumarol
• CYP2C9
• dosing algorithm
• EU-PACT
• Greece
• pharmacogenomics
• VKORC1

Financial & competing interests disclosure

This work was supported by the European Commission Seventh Framework Program (HEALTH-F2-2009-223062). G Ragia is an employee at DNALEX S.A. G Kolovou has given talks, attended conferences and participated in trials sponsored by MSD, Amgen, Sanofi, Angelini, Aegerion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the European Commission Seventh Framework Program (HEALTH-F2-2009-223062). G Ragia is an employee at DNALEX S.A. G Kolovou has given talks, attended conferences and participated in trials sponsored by MSD, Amgen, Sanofi, Angelini, Aegerion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.