Effect of clinical and genetic factors on warfarin dose requirements by race with incorporation of additional predictors
| Variable . | Race combined* . | Race stratified . | P§ (race × predictor interaction) . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| European Americans† . | African Americans‡ . | |||||||||
| β . | % Dose change (95% CI) . | P . | β . | % Dose change (95% CI) . | P . | β . | % Dose change (95% CI) . | P . | ||
| Intercept | 1.5456 | — | — | 1.5413 | — | — | 1.4355 | — | — | — |
| African Americans | −0.0686 | −6.63 (−11.08 to −1.96) | .006 | — | — | — | — | — | — | — |
| Age, y | −0.0069 | −0.68 (−0.81 to −0.56) | <.001 | −0.0062 | −0.62 (−0.79 to −0.45) | <.001 | −0.0071 | −0.71 (−8.69 to −5) | <.001 | .53 |
| BSA, per m2 | 0.4127 | 51.09 (40.10 to 62.94) | <.001 | 0.4006 | 49.27 (35.69 to 64.21) | <.001 | 0.4375 | 54.89 (8.26 to 14.95) | <.001 | .65 |
| CKD|| | −0.0860 | −8.24 (−10.94 to −5.47) | <.001 | −0.1156 | −10.92 (−14.54 to −7.15) | <.001 | −0.0668 | −6.46 (−10.37 to −2.38) | .002 | .10 |
| Amiodarone use | −0.2230 | −19.99 (−24.85 to −14.81) | <.001 | −0.1926 | −17.52 (−23.37 to −11.23) | <.001 | −0.2977 | −25.75 (−33.81 to −16.7) | <.001 | .13 |
| CYP2C9*2¶ | −0.2042 | −18.47 (−22.40 to −14.33) | <.001 | −0.2312 | −20.64 (−24.66 to −16.41) | <.001 | 0.0294 | 2.98 (−10.52 to 18.53) | .68 | <.001 |
| CYP2C9*3¶ | −0.4282 | −34.83 (−39.08 to −30.29) | <.001 | −0.4162 | −34.05 (−38.52 to −29.24) | <.001 | −0.4753 | −37.83 (−48.92 to −24.33) | <.001 | .52 |
| VKORC1¶ | −0.3098 | −26.64 (−29.02 to −24.18) | <.001 | −0.3416 | −28.94 (−31.49 to −26.29) | <.001 | −0.2231 | −19.99 (−25.53 to −14.05) | <.001 | .003 |
| CYP4F2¶ | 0.0448 | 4.58 (0.97 to 8.31) | .01 | 0.0573 | 5.89 (1.9 to 10.05) | .004 | 0.0122 | 1.23 (−6.32 to 9.38) | .76 | .26 |
| rs12777823# | −0.0789 | −7.59 (−11.32 to −3.70) | .0002 | −0.0229 | −2.26 (−7.44 to 3.21) | .41 | −0.1307 | −12.26 (−17.55 to −6.62) | <.001 | .006 |
| CYP2C9*5,6,11# | −0.1796 | −16.44 (−28.47 to −2.38) | .02 | — | — | — | −0.1304 | −12.23 (−25.08 to 2.83) | .11 | — |
| Variable . | Race combined* . | Race stratified . | P§ (race × predictor interaction) . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| European Americans† . | African Americans‡ . | |||||||||
| β . | % Dose change (95% CI) . | P . | β . | % Dose change (95% CI) . | P . | β . | % Dose change (95% CI) . | P . | ||
| Intercept | 1.5456 | — | — | 1.5413 | — | — | 1.4355 | — | — | — |
| African Americans | −0.0686 | −6.63 (−11.08 to −1.96) | .006 | — | — | — | — | — | — | — |
| Age, y | −0.0069 | −0.68 (−0.81 to −0.56) | <.001 | −0.0062 | −0.62 (−0.79 to −0.45) | <.001 | −0.0071 | −0.71 (−8.69 to −5) | <.001 | .53 |
| BSA, per m2 | 0.4127 | 51.09 (40.10 to 62.94) | <.001 | 0.4006 | 49.27 (35.69 to 64.21) | <.001 | 0.4375 | 54.89 (8.26 to 14.95) | <.001 | .65 |
| CKD|| | −0.0860 | −8.24 (−10.94 to −5.47) | <.001 | −0.1156 | −10.92 (−14.54 to −7.15) | <.001 | −0.0668 | −6.46 (−10.37 to −2.38) | .002 | .10 |
| Amiodarone use | −0.2230 | −19.99 (−24.85 to −14.81) | <.001 | −0.1926 | −17.52 (−23.37 to −11.23) | <.001 | −0.2977 | −25.75 (−33.81 to −16.7) | <.001 | .13 |
| CYP2C9*2¶ | −0.2042 | −18.47 (−22.40 to −14.33) | <.001 | −0.2312 | −20.64 (−24.66 to −16.41) | <.001 | 0.0294 | 2.98 (−10.52 to 18.53) | .68 | <.001 |
| CYP2C9*3¶ | −0.4282 | −34.83 (−39.08 to −30.29) | <.001 | −0.4162 | −34.05 (−38.52 to −29.24) | <.001 | −0.4753 | −37.83 (−48.92 to −24.33) | <.001 | .52 |
| VKORC1¶ | −0.3098 | −26.64 (−29.02 to −24.18) | <.001 | −0.3416 | −28.94 (−31.49 to −26.29) | <.001 | −0.2231 | −19.99 (−25.53 to −14.05) | <.001 | .003 |
| CYP4F2¶ | 0.0448 | 4.58 (0.97 to 8.31) | .01 | 0.0573 | 5.89 (1.9 to 10.05) | .004 | 0.0122 | 1.23 (−6.32 to 9.38) | .76 | .26 |
| rs12777823# | −0.0789 | −7.59 (−11.32 to −3.70) | .0002 | −0.0229 | −2.26 (−7.44 to 3.21) | .41 | −0.1307 | −12.26 (−17.55 to −6.62) | <.001 | .006 |
| CYP2C9*5,6,11# | −0.1796 | −16.44 (−28.47 to −2.38) | .02 | — | — | — | −0.1304 | −12.23 (−25.08 to 2.83) | .11 | — |
β denotes parameter estimates. Bold font denotes that the parameter estimates are significantly different by race.
CI, confidence intervals.
The referent is a European American with wild-type genotype for the CYP2C9*2; CYP2C9*3; CYP2C9*5, *6, and *11; VKORC1; CYP4F2; and rs12777823 variants, without CKD, and not on amiodarone.
The referent is a European American with wild-type genotype for the CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, and rs12777823 variants, without CKD, and not on amiodarone.
The referent is a African American with wild-type genotype for the CYP2C9*2, CYP2C9*3, CYP2C9*5, *6 and *11,, VKORC1, CYP4F2 and rs12777823 variants, no CKD, and not on amiodarone.
P value for the difference in parameter estimates obtained by including interaction terms of predictors with race (African American vs European American) in the race-adjusted model.
CKD was based on National Kidney Foundation staging using the Modification of Diet in Renal Disease Study equation.2 Patients were categorized into 3 categories: eGFR ≥60 (no CKD or mild CKD stage 1 and 2), eGFR = 30-59 (moderate CKD; stage 3), and eGFR <30 (severe CKD; stage 4 and 5).
CYP2C9*2, CYP2C9*3, CYP4F2, and VKORC1 were included as additive: 0 if no variants, 1 if heterozygous, and 2 if homozygous for the variant allele.
CYP2C9*5, *6, and *11 together and rs12777823 were categorized as 0 if no variants and 1 if heterozygous or homozygous for the variant allele.