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. Author manuscript; available in PMC: 2020 Jun 1.
Published in final edited form as: Clin Pharmacol Ther. 2019 Feb 17;105(6):1477–1491. doi: 10.1002/cpt.1323

Table 3.

Predictive model for logarithm of stable coumarin dose according to patients’ clinical and genetic characteristics

WHITES
Acenocoumarol Warfarin
Variable Parameter estimate (95% Cl) P value R2 test (N = 2,744) R2 validation (N = 1,410) Parameter estimate (95% Cl) P value R2latest (N = 3,016) R2 validation (N = 1,532)
Intercept 4.069 (3.883; 4.256) < 0.0001 0.33 0.28 3.981 (3.887; 4.075) < 0.0001 0.51 0.52
Agea −0.014 (−0.015; −0.012) < 0.0001 −0.009 (−0.010; −0.008) < 0.0001
BMIa −0.002 (−0.006; 0.002) 0.28 0.010 (0.008; 0.012) < 0.0001
Male gender 0.014 (−0.024; 0.052) 0.47 0.123 (0.098; 0.148) < 0.0001
Indication for treatmentb 0.000 (−0.042; 0.042) 0.98 −0.043 (−0.069; −0.017) 0.001
CYP2C9 *2 1-allele −0.190 (−0.232; −0.147) < 0.0001 −0.231 (−0.261; −0.202) < 0.0001
CYP2C9 *2 2-alleles −0.359 (−0.484; −0.234) < 0.0001 −0.513 (−0.600; −0.426) < 0.0001
CYP2C9 *3 1-allele −0.394 (−0.446; −0.342) < 0.0001 −0.387 (−0.425; −0.350) < 0.0001
CYP2C9 *3 2-alleles −1.214 (−1.522; −0.907) < 0.0001 −1.316 (−1.502; −1.131) < 0.0001
VK0RC1 AG −0.291 (−0.332; −0.249) < 0.0001 −0.266 (−0.292; −0.240) < 0.0001
VK0RC1 AA −0.762 (−0.816; −0.708) < 0.0001 −0.666 (−0.704; −0.629) < 0.0001
CYP4F2 CT 0.018 (−0.022; 0.058) 0.39 0.073 (0.047; 0.098) < 0.0001
CYP4F2 TT 0.100 (0.041; 0.159) 0.0009 0.191 (0.147; 0.235) < 0.0001
ASIANS
Acenocoumarol Warfarin
Variable Parameter estimate P value R2 test (N=0) R2 validation (N=0) Parameter estimate P value R2 test (N = 292) R2 validation (N = 146)
Intercept - - - - 3.484 (3.112; 3.855) < 0.0001 0.45 0.42
Agea - - -0.005 (−0.008; −0.001) 0.02
BMIa - - 0.014 (0.004; 0.023) 0.004
Male gender - - 0.058 (−0.050; 0.167) 0.29
Indication for treatmentb - - −0.027 (−0.139; 0.084) 0.63
CYP2C9*2 1-allele - - −0.114 (−0.351; 0.124) 0.35
CYP2C9*2 2-alleles - - - -
CYP2C9*3 1-allele - - −0.224 (−0.428; −0.020) 0.03
CYP2C9*3 2-alleles - - −1.065 (−1.717; −0.412) 0.002
VK0RC1 AG - - −0.422 (−0.574; −0.271) < .0001
VK0RC1 AA - - −0.827 (−0.975; −0.679) < .0001
CYP4F2 CT - - 0.117 (0.003; 0.231) 0.04
CYP4F2 TT - - 0.124 (−0.075; 0.324) 0.22
BLACKS
Acenocoumarol Warfarin
Variable Parameter estimate P value R2test (/V=0) R2 validation (N = 0) Parameter estimate P value R2 test (N = 534) R2 validation (N = 288)
Intercept - - - - 3.875 (3.692; 4.061) < 0.0001 0.30 0.22
Agea - - −0.009 (−0.011; −0.006) < 0.0001
BMIa - - 0.010 (0.007; 0.015) < 0.0001
Male gender - - 0.152 (0.086; 0.219) < 0.0001
Indication for treatmentb - - −0.090 (−0.160; −.0183) 0.01
CYP2C9*2 1-allele - - −0.007 (−0.149;0.133) 0.93
CYP2C9*2 2-alleles - - - -
CYP2C9 *3 1-allele - - −0.469 (−0.666; −0.270) < 0.0001
CYP2C9 *3 2-alleles - - - -
CYP2C9 *5 1-allele - - −0.436 (−0.736; −0.137) 0.005
CYP2C9 *5 2-alleles - - - -
VK0RC1 AG - - −0.284 (−0.585; −0.020) 0.07
VK0RC1 AA - - −0.281 (−0.588; −0.020) < 0.0001
CYP4F2 CT - - −0.0382 (−0.124; 0.050) 0.40
CYP4F2 TT - - 0.300 (−0.068; 0.664) 0.11

Statistical test for model fit (R2) is reported both for the test and validation cohorts. Due to significant heterogeneity, separate models are reported for different ethnic groups and drugs. BMI, body mass index; CI, confidence interval; CYP, cytochrome P450.

a

Estimate for 1 unit increase.

b

Estimate for the following indication for treatment: fibrillation/flutter, cardiomyopathy/left ventricular dilation, postorthopedic.