CYP2C9 Polymorphism and Unstable Anticoagulation with Warfarin in Patients Within the First 3 Months Following Heart Valve Replacement

BACKGROUND: Warfarin dose requirements are partly determined by common single nucleotide polymorphisms in VKORC1 and CYP2C9 genes. OBJECTIVES: The aim of this study was to investigate how the presence of allelic variants in CYP2C9 affects the stability of anticoagulation in patients within the first 3 months following elective heart valve replacement. MATERIAL AND METHODS: In a case-control study we compared 18 consecutive carriers of CYP2C9*2 and/or *3 and 25 well-matched patients with the wild type CYP2C9*1/*1 genotype. The former group was randomly assigned to use coagulometers or monitor international normalized ratio (INR) in local outpatient clinics. Subjects receiving drugs potently interfering with warfarin were ineligible. Anticoagulation with the baseline warfarin regimens based on pharmacogenetic algorithm was assessed by time in the therapeutic INR range (TTR) within the first 3 months following implantation. RESULTS: Carriers of the CYP2C9*2 and/or *3 genotypes were characterized by lower estimated warfarin dose (median, 21 [interquartile range, 21-35] vs. 35 [28-42] mg/week, p=0.02) and actual (27.8±13.2 vs. 46.3±13.9 mg/week, p<0.001), together with lower TTR values (56 [38.6-74.9] vs. 75.4 [58.1-83.6] %, p=0.03) and longer time above the therapeutic range (13.8 [4.9-34.5] vs. 4.5 [0-15.3]%, p=0.047) than patients with the CYP2C9*1/*1 genotype. There were no differences in the estimated and actual warfarin doses, TTR values and adverse events between the self-testing and standard-care subgroups. CONCLUSIONS: The presence of CYP2C9*2 and/or *3 genotypes is associated with unstable warfarin treatment in patients after heart valve replacement, regardless of the type of INR testing.