Table 5.
Adjusted risk ratios regarding the influence of CYP2C9 and VKORC1 on time to attaining anticoagulation endpoints
| Endpoint | CYP2C9 (variant vs. wild-type) | VKORC11173C/T (variant vs. wild-type) | ||
|---|---|---|---|---|
| Unadjusted HR (95% CI) | Adjusted HR (95% CI) | Unadjusted HR (95% CI) | Adjusted HR (95% CI) | |
| Time to first target INR | ||||
| European American | 1.23 (0.96, 1.58) | 1.09 (0.72, 1.65) | 1.11 (0.87, 1.42) | 1.09 (0.80, 1.49) |
| African American | 1.27 (0.87, 1.87) | 1.15 (0.73, 1.83) | 1.11 (0.80, 1.52) | 0.99 (0.69, 1.41) |
| Time to stable dosing* | ||||
| European American | 1.11 (0.85, 1.45) | 0.93 (0.59, 1.48) | 0.96 (0.74, 1.25) | 0.89 (0.63, 1.26) |
| African American | 0.98 (0.63, 1.53) | 0.85 (0.50, 1.43) | 0.98 (0.66, 1.46) | 1.41 (0.90, 2.22) |
| Time to INR >4 during first 30 days*$ | ||||
| European American | 1.23 (0.83, 1.81) | 2.84 (0.91, 8.85) | 2.67 (1.57, 4.57) | 3.75 (1.52, 9.30) |
| African American | 1.16 (0.56, 2.44) | 0.77 (0.19, 3.09) | 1.63 (0.93, 2.83) | 1.26 (0.57, 2.76) |
| Time to INR >4 prior to stabilization**$ | ||||
| European American | 1.33 (0.98, 1.81) | 2.15 (0.90, 5.13) | 2.28 (1.55, 3.35) | 2.69 (1.32, 5.47) |
| African American | 1.00 (0.60, 1.69) | 0.87 (0.34, 2.21) | 1.24 (0.83, 1.86) | 1.08 (0.69, 1.68) |
| Time to INR >4 during duration of follow-up*$ | ||||
| European American | 1.27 (1.03, 1.58) | 1.82 (0.97, 3.43) | 1.68 (1.33, 2.11) | 1.91 (1.27, 2.89) |
| African American | 1.11 (0.83, 1.49) | 0.66 (0.34, 1.29) | 0.93 (0.71, 1.23) | 0.72 (0.43, 1.20) |
CYP2C9 Variant genotype includes one or more (*2, *3, *5, *6 and *11) alleles.
Variant VKORC11173C/T includes ‘TT or CT’
All models adjusted for age, gender, BMI, CYP2C9, VKOR1173C/T, interaction between CYP2C9*VKOR1173C/T, number of comorbid conditions, vitamin K intake, drug interactions (e.g amiodarone), clinic site, education, income, indication, insurance and current smoking.
Models adjusted for Vscore, the variance growth rate, a measure of INR variability up to the preceding visit was also included in analyses of time to stable dosing and time to INR >4.
Models adjusted for correlation between repeat episodes of INR>4 within the patient
Median time to stabilization (95 days, Intraquartile range 42–175 days) was used to assess genotype related risk of over-anticoagulation. Analyses based on individual time to stabilization could not be conducted due to model non-convergence on stratification by race among African Americans.