Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With CYP2C9 and VKORC1 Polymorphisms

Background: Dose requirements of vitamin K antagonists are associated with CYP2C9 and VKORC1, but, compared to warfarin, less data is available about phenprocoumon. Furthermore, the effects on dose stability and anticoagulation quality are still unclear. Methods: Aim was to scrutinize phenprocoumon dose requirements, dose stability and anticoagulation quality in association to CYP2C9 and VKORC1 in a natural cohort of elderly primary care patients. As a subgroup within the IDrug study, phenprocoumon treated patients with at least two INR values within three months before enrollment (n = 209) were analyzed concerning average weekly dose, standard deviation of weekly dose (intra-subject variability), constant dose (yes/no), average INR and TTR grouped by CYP2C9 and VKORC1 (and combinations). Results: Average weekly dose per patient was 14.4 +/- 5.3 mg, 11.9 +/- 4.0 mg and 11.2 +/- 4.3 mg in CYP2C9 wildtypes, *2 and *3 carriers (p < .0001) and 16.0 +/- 4.2 mg, 13.3 +/- 5.1 mg and 8.0 +/- 2.7 mg per week in VKORC1 CC, CT and TT genotypes, respectively (p < .0001). Significant differences concerning intra-subject variability were detected among all groups (p