Table 3 |.

Comparison of warfarin pharmacogenomic trials

Trial	Participants	Comparator group	Genetic polymorphisms tested	Loading dose	Primary end point	Outcome	Ref.
EU-PACT (2013)	Adults from Sweden or the UK (n = 455; 98.5% white) who were newly starting warfarin for atrial fibrillation or venous thromboembolism	Fixed dose of 10 mg on day 1 (or 5 mg if aged >75 years), then 5 mg on days 2 and 3, then dose guided by INR	CYP2C9*2 and *3, VKORC1 −1639G>A	Yes, loading dose algorithm used on days 1–3 in the genotype-guided group; 10 mg dose given on day 1 for patients aged ≤75 years in the control group	Percent of time with an INR of 2.0–3.0 during the initial 12 weeks of warfarin therapy	Mean percent time in INR range was 67.4% in the genotype-guided group and 60.3% in the control group (P < 0.001)	89
COAG (2013)	Adults from the USA newly initiating warfarin treatment with a target INR of 2.0–3.0 (n = 1,015; 27% Black, 73% non-Black)	Clinical algorithm-guided dosing	CYP2C9*2 and *3, VKORC1 −1639G>A	No, but CYP2C9 variants were ignored for the initial dose in the genotype-guided group	Percent of time with an INR of 2.0–3.0 from day 4 or 5 through to day 28 of warfarin therapy	All patients: mean percent time in INR range was 45.2% in the genotype-guided group and 45.4% in the clinically-guided group (P = 0.91); Black patients: mean percent time in INR range was 35.2% in the genotype-guided group and 43.5% in the clinically guided group (P = 0.01)	122
GIFT (2017)	Patients aged ≥65 years undergoing elective total-hip or total-knee arthroplasty (n = 1,650; 91% white, 6% Black)	Clinical algorithm-guided dosing	CYP2C9*2 and *3, VKORC1 −1639G>A, CYP4F2*3	No, but CYP2C9 variants were ignored for the first 2 days of therapy in the genotype-guided group	Composite of major bleeding, INR ≥4, venous thromboembolism or death	10.8% in the genotype-guided group and 14.7% in the clinically guided group had at least one end point (relative rate 0.73, 95% CI 0.56–0.95, P = 0.02)	121

INR, international normalized ratio.