Pharmacogenetic variants influence vitamin K anticoagulant dosing in patients with mechanical prosthetic heart valves.

Background: Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to quantify the relative effects of VKORC1, CYP2C9 and CYP4F2 genotypes in predicting VKA dosing. Materials & methods: A total of 506 South Indian patients with mechanical prosthetic heart valves who were prescribed oral VKAs, such as warfarin or acenocoumarol, were genotyped. The discriminatory ability of mutant genotypes to predict dose categories and bleeding events was assessed using regression analysis. Results: The VKORC1 rs9923231, CYP2C9*3 and CYP4F2*3 mutant genotypes significantly influenced VKA-dose requirements and explained 27.47% of the observed dose variation. Conclusion: These results support pharmacogenetic screening for initial VKA dosing among South Indian patients with mechanical prosthetic heart valves.