Warfarin Metabolites in Patients Following Cardiac

Authors: Agata Bryk Ewa Wypasek Magdalena Awsiuk Dorota Maj Anetta Undas

Publish Date: 2015/05/19

Volume: 29, Issue: 3, Pages: 257-264

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Abstract

Warfarin a racemic mixture of S and Renantiomers is the cornerstone of therapy in patients following cardiac valve replacement Swarfarin is metabolized to 7Shydroxywarfarin by the cytochrome P450 isoform 2C9 encoded by CYP2C9 gene Rwarfarin is metabolized by multiple cytochromes P450 We sought to assess the impact of clinical and genetic factors on circulating warfarin metabolites following valve implantationVenous blood was collected from 120 patients after 3 months since elective mitral and/or aortic valve replacement Plasma Swarfarin Rwarfarin S7hydroxywarfarin and R7hydroxywarfarin were determined using highperformance liquid chromatography The S7hydroxywarfarin/Swarfarin and Swarfarin/Rwarfarin S/R ratios along with warfarin sensitivity index WSI defined as INR/Swarfarin ratio were calculated Vitamin K epoxide reductase complex subunit 1 VKORC1 c1639A CYP2C93 and CYP2C92 alleles were determined using realtime polymerase chain reactionThe Swarfarin was higher in former smokers p = 0047 and the VKORC1 c1639A allele carriers p  00001 The S7hydroxywarfarin was lower in carriers of the VKORC1 c1639A allele p = 00005 and CYP2C93 p = 0047 The S7hydroxywarfarin/Swarfarin ratio was lower in the carriers of CYP2C93 p = 0008 but not in those with VKORC1 –c1639A allele The S/R ratio was higher in patients with hypertension p = 001 The independent predictors of elevated S/R ratio defined as the upper quartile were diabetes p = 0045 CYP2C93 p  00001 and CYP2C92 p = 00002 The independent predictors of elevated WSI were current smoking p = 0049 implantation of mechanical valve p = 0006 and VKORC1c1639A allele p = 0007

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