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Coumarin derivatives are commonly prescribed for the treatment and prevention of thromboembolic events [1]. Anticoagulation therapy with coumarins requires frequent monitoring of the International Normalized Ratio (INR), an indicator of the clotting tendency of blood, to maintain within a narrow therapeutic range. For patients with atrial fibrillation, the INR target range is normally 2.0-3.0, with some exceptions such as 2.5-3.5 in The Netherlands [2]. Wide inter- and intra-patient variability in dose requirement exists, which makes it difficult to predict the right dose. INR values below the therapeutic range lead to loss of efficacy and an increased risk of thromboembolic events, while INR values above the therapeutic range lead to toxicity with an increased risk of bleeding events. The latter can be minor or major and life-threatening or fatal, such as intracranial hemorrhage (ICH) [3]. The variation in dose requirements can be explained by several factors, including age, weight, height, vitamin K intake and concomitant medication; however, genetic factors also explain a substantial proportion of this variability [4]. Genotyping the CYP2C9 and VKORC1 genes may help to predict the required coumarin dose prior to treatment of the patients [5]. CYP2C9 encodes the main metabolizing enzyme of coumarins, CYP2C9, and VKORC1 encodes the pharmacodynamic target enzyme for coumarins, VKORC1. By prescribing a dose that is based on genotype and clinical factors, it is anticipated that patients will both reach a therapeutic INR quicker and maintain within range for longer. This could decrease the risk of adverse events, including stroke and bleeding; however, supporting evidence from appropriately powered clinical trials are hitherto unavailable.
For the implementation of pharmacogenetic testing in practice, further evidence of the clinical effectiveness and cost-effectiveness is necessary. Currently, two major clinical trials are ongoing to investigate the former [6,7], and an economic analysis is planned to estimate the incremental cost-effectiveness of the new dosing strategy compared with standard care (i.e., a nongenotype-guided dosing regimen). Several cost-effectiveness analyses of genotyping have previously been performed, but with limited conclusions about their economic value, principally because of the uncertainty in the clinical evidence [8-16]. Furthermore, most of the cost-effectiveness studies were conducted in the USA, where anticoagulation services are organized differently from European countries. However, even among European countries, different models of care apply. In some...