Impact of CYP2C9 genetic polymorphism on warfarin sensitivity among acutely ill patients

CYP2C9 allelic variants, CYP2C9*2 and CYP2C9*3 are associated with impaired metabolism of S-warfarin. However, the significance of this impairment has not been studied among acutely ill, hospitalized patients. The purpose of the study was to evaluate the effect of CYP2C9 mutant alleles on Warfarin Sensitivity Index, (WSI, defined as the ratio of warfarin dose to INR) among acutely-ill patients. Fifty-three patients, mean age (±SD) 68.6 (±13.9) years, 43.3% with NYHA class III-IV heart failure, 27.8% treated with antibiotics and 20.7% with amiodarone, were studied. The frequencies of CYP2C9*2 and CYP2C9*3 were 16.6% and 13.0%, respectively. CYP2C9*3, but not CYP2C9*2 carriers, had a significantly lower WSI, as compared to patients who are not carriers of this allele (1.13 vs 2.43 mg, 95% CI 0.69-1.56 vs 1.76-3.10, respectively, p<0.007). We therefore conclude that even among acutely ill patients, the variability in warfarin sensitivity may be partially attributed to CYP2C9 genetic polymorphism, and in particular to CYP2C9*3 allele.