Extrapolation of acenocoumarol pharmacogenetic algorithms

Introduction: Acenocoumarol (ACN) has a narrow therapeutic range that is especially difficult to control at the start of its administration. Various dosing pharmacogenetic-guided dosing algorithms have been developed, but further work on their external validation is required. The aim of this study was to evaluate the extrapolation of pharmacogenetic algorithms for ACN as an alternative to the development of a specific algorithm for a given population.

Material and methods: The predictive performance, deviation, accuracy, and clinical significance of five pharmacogenetic algorithms (EU-PACT, Borobia, Rathore, Markatos, Krishna Kumar) were compared in 189 stable ACN patients representing all indications for anticoagulant treatment.

Results: The correlation between the dose predictions of the five pharmacogenetic models ranged from 7.7 to 70.6% and the percentage of patients with a correct prediction (deviation ≤20% from actual ACN dose) ranged from 5.9 to 40.7%. EU-PACT and Borobia pharmacogenetic dosing algorithms were the most accurate in our setting and evidenced the best clinical performance.

Conclusions: Among the five models studied, the EU-PACT and Borobia pharmacogenetic dosing algorithms demonstrated the best potential for extrapolation.