Cost-effectiveness of pharmacogenetic-guided dosing of phenprocoumon in atrial fibrillation

Background: Genotyping patients for polymorphisms in the CYP2C9 gene, encoding for the main metabolizing enzyme, cytochrome P450 2C9 (CYP2C9), and the VKORC1 gene, encoding for the target enzyme Vitamin K epoxide reductase multiprotein complex 1 (VKORC1) helps to predict the required coumarin dose prior to treatment initiation. Objectives: To investigate the cost-effectiveness of pharmacogenetic-guided phenprocoumon dosing vs. standard anticoagulation care, in Dutch patients with atrial fibrillation. Methods: Using a decision-analytic Markov model we estimated the incremental effectiveness (in qualityadjusted life-years, QALYs) and cost-effectiveness of pharmacogenetic-guided phenprocoumon therapy vs. standard care. Time spent in different international normalized ratio (INR) ranges was used to estimate the risk of thromboembolic and bleeding events. The quality of life of patients in different health states was derived from literature. Costs were determined from a third-party payer perspective and a lifetime horizon was used. Additionally, sensitivity analyses for a selection of variables were performed. Results: Compared with standard care, the pharmacogenetic- guided dosing strategy increased the QALYs only very slightly (2 days) and increased costs by €15. The incremental cost-effectiveness ratio was €2658 per QALY gained. In sensitivity analyses, the cost of genotyping had the largest influence on the cost-effectiveness ratio. In a probabilistic sensitivity analysis, the incremental costs of genotype-guided dosing were <€20,000 per QALY gained in 78.2% of the simulations. Conclusions: Pharmacogenetic-guided dosing of phenprocoumon has the potential to increase health slightly and may be able to achieve this in a cost-effective way. Because of the many uncertainties in for example the costs of the genetic test or the effectiveness of genotyping, it is too early to conclude whether or not patients starting phenprocoumon should be genotyped.