The WARG warfarin dose algorithm
| Coefficients . | Estimate . | Standard error . | P . |
|---|---|---|---|
| Intercept | 9.46832 | 0.11867 | < 2 × 10−16 |
| VKORC1 rs9923231 G/G | 0 | ||
| VKORC1 rs9923231 A/G | −0.90112 | 0.04959 | < 2 × 10−16 |
| rs9923231 A/A | −2.01863 | 0.06799 | < 2 × 10−16 |
| CYP2C9*1/*1 | 0 | ||
| *1/*2 | −0.50836 | 0.05811 | < 2 × 10−16 |
| *1/*3 | −0.97546 | 0.07077 | < 2 × 10−16 |
| *2/*2 | −1.10204 | 0.19767 | 3.0 × 10−8 |
| *2/*3 | −1.74761 | 0.20391 | < 2 × 10−16 |
| *3/*3 | −3.40061 | 0.33091 | < 2 × 10−16 |
| Age, y | −0.03686 | 0.00172 | < 2 × 10−16 |
| Male sex* | 0 | ||
| Female sex* | −0.27698 | 0.04682 | 4.2 × 10−9 |
| Interaction × number of drugs that increase INR† | −0.06992 | 0.01867 | .001 |
| Coefficients . | Estimate . | Standard error . | P . |
|---|---|---|---|
| Intercept | 9.46832 | 0.11867 | < 2 × 10−16 |
| VKORC1 rs9923231 G/G | 0 | ||
| VKORC1 rs9923231 A/G | −0.90112 | 0.04959 | < 2 × 10−16 |
| rs9923231 A/A | −2.01863 | 0.06799 | < 2 × 10−16 |
| CYP2C9*1/*1 | 0 | ||
| *1/*2 | −0.50836 | 0.05811 | < 2 × 10−16 |
| *1/*3 | −0.97546 | 0.07077 | < 2 × 10−16 |
| *2/*2 | −1.10204 | 0.19767 | 3.0 × 10−8 |
| *2/*3 | −1.74761 | 0.20391 | < 2 × 10−16 |
| *3/*3 | −3.40061 | 0.33091 | < 2 × 10−16 |
| Age, y | −0.03686 | 0.00172 | < 2 × 10−16 |
| Male sex* | 0 | ||
| Female sex* | −0.27698 | 0.04682 | 4.2 × 10−9 |
| Interaction × number of drugs that increase INR† | −0.06992 | 0.01867 | .001 |
VKORC1 G/G and CYP2C9*1/*1 were used as the reference genotypes in the algorithm. The model predicts the square root of dose; hence dose (mg/week) is obtained by squaring the result. Example: A 50-year-old male with no interacting drugs is genotyped as VKORC1 A/G and CYP2C9*1/*3. The resulting square root of weekly dose is: 9.46832 – (0.90112 for A/G) – (0.97546 for *1/*3) – (0.03686 × 50 y) = 5.74874. To obtain his predicted weekly dose, transform by squaring the result: 5.748742 ≈ 33 mg/week.
Sex is a substitute for body weight and height, which are not available in the WARG cohort.
Take the number of interacting drugs that potentially increase INR and multiply by −0.06992. Drugs that decrease the effect of warfarin also have a large impact on the individual, but are not included in the algorithm, since too few were present in the cohort to get reliable results.