Table 3. . Pharmacogenetic dosing algorithms and their performance in interventional studies.
| Study (year) | n‡ | Treatment of race in the model | Clinical and genetic predictors† | R2 explained (%) | PTTR (%) (genotype guided vs clinical/standard) | Ref. | ||
|---|---|---|---|---|---|---|---|---|
| Genetic | Clinical | Total | ||||||
| Hillman et al. (2005) | E: 38 | Restricted to EA | Age, BSA, indication of therapy, diabetes, CYP2C9*2, *3 | – | – | 34 | 42, 42 | [83] |
| Anderson et al. (2007) (CoumaGen) | E: 189 | Restricted to EA | Age, gender, weight, amiodarone, CYP2C9*2, *3; VKORC1 -1639A | 32 | 15 | 47 | 70, 69 | [86] |
| McMillin et al. (2010) | E: 206 | Restricted to EA | Age, height, CYP2C9*2, *3; VKORC1 -1639A | 18 | – | – | 43, 45 | [102] |
| Burmester et al. (2011) | E: 225 | Restricted to EA | Age, gender, BSA, valve replacement, CYP2C9*2, *3; VKORC1 -1639A, CYP4F2*3 Age*Valve replacement as well in the clinical arm |
– | 35 | 65 | 29, 29 | [81] |
| Anderson et al. (2012) (CoumaGen II) | E: 2744 | Restricted to EA | Age, height, weight, race, amiodarone, enzyme inducers, CYP2C9*2, *3; VKORC1 -1639A | 37 | 13 | 49 | 71, 59 | [84] |
| Borgman et al. (2012) (PerMIT) | E: 24 | Restricted to EA | Age, gender, bodyweight, CYP2C9*2, *3; VKORC1 -1639A | – | – | – | 63, 55 | [85] |
| Jonas et al. (2013) (WARFPGX) | E: 79 | Adjusted for race | Age, race, BSA, smoking status, indication for warfarin, target INR, amiodarone, CYP2C9*2, *3; VKORC1 -1639A | – | – | – | 45, 49 | [78] |
| A: 30 | ||||||||
| Pirmohamed et al. (2013) (EU-PACT) | E: 447 | Unadjusted for race | Age, height, weight, amiodarone (BSA, log INR, target INR, dose given 2–4 days before INR measurement), CYP2C9*2, *3; VKORC1 -1639A | – | – | – | 67, 60 | [80] |
| A: 5 | ||||||||
| Kimmel et al. (2013) (COAG) | E: 675 | Adjusted for race | Age, race, smoking status, BSA, amiodarone, target INR, DVT/PE (diabetes, stroke, fluvastatin, log INR, dose given 2–4 days before INR measurement), CYP2C9*2, *3; VKORC1 -1639A |
– | 17 (51) | 52 (75) | 49, 46 | [79] |
| A: 275 | – | 33 (50) | 21 (40) | 35, 44 | ||||
| Pengo et al. (2015) | E: 180 | Restricted to EA | Age, BSA, CYP2C9*2, *3; VKORC1-1639A; CYP4F2*3 | – | – | 50 | 52, 53 | [87] |
| Gage et al. (2017) (GIFT) | E: 1454 | Adjusted for race | Age, race, BSA, current smoking, baseline and target INR, indication for warfarin, amiodarone, azoles and other antibiotics, CYP2C9*2, *3; VKORC1-1639A; CYP4F2*3 | – | – | – | 55, 51 | [82] |
| A: 102 | – | – | – | 51, 51 | ||||
†Parentheses include variables that were part of the dose revision algorithm, in addition to the variables listed in that cell that were part of the dose initiation algorithm.
‡Individuals of other race/ethnic groups are not listed in this table.
A: African descent; BSA: Body surface area; COAG: Clarification of Oral Anticoagulation through Genetics; DVT/PE: Deep vein thrombosis or pulmonary embolism; E: European descent; INR: International Normalized Ratio; PTTR: Percentage time in therapeutic range; COAG: Clarification of Optimal Anticoagulation through Genetics; EU-PACT: European Pharmacogenetics of Anticoagulant Therapy; GIFT: Genetics Informatics Trial of warfarin; PerMIT: Personalized Medicine Interface Tool for genotype-based warfarin dosing; WARFPGX: Genotype-guided warfarin therapy trial.