To develop an acenocoumarol (ACN) dosing algorithm for patients with atrial fibrillation or venous thromboembolism, considering the influence on the stable ACN dose of clinical factors and gene polymorphisms, including CYP2C9*2/*3, VKORC1, CYP4F2*3, ABCB1, APOE, CYP2C19*2/*17, and GGCX.
Methods and results
A retrospective observational study was carried out to obtain clinical and pharmacogenetic dose algorithms by multiple linear regression of results in a cohort of 134 patients under treatment with a stable ACN dose for atrial fibrillation or venous thromboembolism and to test them in an independent validation cohort of 30 patients.
The pharmacogenetic dosing algorithm included CYP2C9, VKORC1, and APOE, which explained 56.6% of the variability in the stable ACN dose. Lower deviation from the stable dose and increased accuracy were shown by the pharmacogenetic algorithm, which correctly classified 67% of patients with a deviation of up to 20%.
The variability in the stable ACN dose was better explained by a pharmacogenetic algorithm including clinical and genetic factors (CYP2C9, VKORC1, and APOE) than by a clinical algorithm, providing a more accurate dosage prediction.