Influence of CYP2C9 polymorphism on the fall in International Normalized Ratio in patients interrupting warfarin therapy before elective surgery

Abstract

Patients on warfarin are normally required to stop treatment for a fixed number of days prior to an invasive procedure. However, the anticoagulant activity of warfarin subsides at different rates among different patients. The aim of this study was to investigate the potential influence of CYP2C9 polymorphism on the variable rate of fall in the International Normalized Ratio (INR) in patients withdrawing from warfarin treatment prior to elective surgery. One hundred and fifty-two patients aged 43-93years were recruited. Demographic data on age, height, weight, gender, daily warfarin dose, indication for anticoagulation therapy, medical diagnosis, surgical operation planned and concomitant medication were recorded. A blood sample was taken for later CYP2C9 genotyping. For patients with two CYP2C9 variant alleles (CYP2C9*2*2 or CYP2C9*2*3), the odds of having an INR of ≥1.5 before the planned day of surgery were 8.64 times greater (95% confidence interval [CI]2.25-33.25) than for other patients. Multiple regression analysis revealed that the rate of fall in the INR was reduced in the presence of two CYP2C9 variant alleles, as well as increasing patient age, weight and number of comorbidities, and increased with increasing initial INR (F5,132 =242.9, P<0.0001), all of which accounted for ~90% of the interindividual variability in the fall in INR. A genotype-guided protocol to tailor warfarin withdrawal according to an individual patient's CYP2C9 genotype could reduce cancellation or delays of planned procedures, and could also be beneficial when transitioning patients from warfarin to one of the new oral anticoagulants.