The Combined Effects of Clinical Factors and CYP2C9 and VKORC1 Gene Polymorphisms on Initiating Warfarin Treatment in Patients after Cardiac Valve Surgery

Background and aim of the study: Recent studies have shown that, after heart valve surgery, patients may require a more precise warfarin dosage than their non-surgical counterparts. The study aim was to analyze the influence of certain clinical factors and CYP2C9 and VKORC1 gene polymorphisms on the efficacy of initiation of warfarin treatment in patients after cardiac valve surgery.
Methods: Following heart valve surgery, a total of 185 patients was genotyped for the CYP2C9*1, *2, *3 alleles and for VKORC1 (G-1639A) gene promoter polymorphism.
Results: A hierarchical stepwise multivariate linear regression model was used to evaluate factors affecting the optimal warfarin dosage. Patient age and body weight, together with hepatic malfunction in the cohort population, accounted for 12% of the

variation in warfarin dosage (R² = 0.119). The introduction of concomitant medications, more than doubled (R² = 0.316) the accuracy of the dosage algorithm. Medications such as cephalosporin, amiodarone, loop diuretics, ibuprofen or diclofenac, omeprazole and β-blockers had significant effects on the warfarin daily dosage in this model. However, the greatest accuracy was obtained when the patient’s CYP2C9 and VKORC1 genotype was introduced into the formula as the critical factor (R² = 0.429).
Conclusion: The study results suggested that, after cardiac valve surgery, by combining the clinical, genetic and anthropometric data of a patient, the warfarin dose may be estimated to 43% accuracy at the initiation of anticoagulant therapy.

The Journal of Heart Valve Disease 2012;21:628-635