title: Clinical Predictors Associated With Warfarin Sensitivity.
abstract: Our study aimed to identify predictors of warfarin sensitivity like demographic, clinical, and genetic data from a previously collected cohort of patients (n = 4272) with a stable warfarin dose who were able to achieve an observed international normalized ratio of 2-3. Predictors of warfarin sensitivity (dose ≤21 mg/wk) were identified using a 2-stage approach. First, bivariate analysis, using analysis of variance for continuous variables and χ test for categorical variables, was performed to identify possible predictors of warfarin sensitivity (P < 0.05). Second, logistic regression with backward stepwise selection was then performed using predictors identified in bivariate analysis step to produce final model containing independent predictors at P < 0.05. Increased warfarin sensitivity was associated with increased age; CYP2C9 genotypes 2/3, 1/3, and 3/3; VKORC1 genotypes AA and AG; and amiodarone use. Decreased warfarin sensitivity (ie, weekly warfarin dose of >21 mg) was associated with increased height, increased weight, having diabetes mellitus, VKORC1 genotype GG, and CYP2C9 genotype 1/1. In conclusion, we identified patients' characteristics associated with warfarin sensitivity. This project is expected to improve patient care by identifying patients who need a low warfarin dose before warfarin administration. Early identification of this subset of patients helps minimize the incidence of bleeding.
authors.affiliation: Department of Biopharmaceutics and Clinical Pharmacy, The University of Jordan, Amman, Jordan.
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Saleh
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000638:Amiodarone / Q000008:administration & dosage; D001827:Body Height; D001835:Body Weight; D002648:Child; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D016015:Logistic Models; D008297:Male; D008661:Metabolism, Inborn Errors / Q000453:epidemiology*; D008875:Middle Aged; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D055815:Young Adult
chemical_list: D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D000638:Amiodarone