Table 6.

Randomized studies comparing genotype based warfarin therapy (Target INR 2–3) to standard medical care in assessing warfarin response

		Caraco et al, 2007a	Anderson et al, 2007 b
Population Characteristics
Number of subjects evaluated		191 (95 PG, 96 STD) Ф	200 (101 PG, 99 STD)Ф
Racial/ Ethnic Group		100% European descent	95% European descent
Study Characteristics
Follow- up (Mean ± SD)		Different in two arms	46 ± 32 days
INR assessment schedule		Daily until target INR is sustained for 2 days then at least twice weekly until stabilized	Days 0, 3, 5, 8, 21, 60, 90, and as clinically indicated
Polymorphisms assessed
CYP2C9		*2, *3	*2, *3
VKORC1		NE	1173C/T
Genotype guided therapy:
Improved dose prediction		NE	Yes, p<0.001
% Variance in dose predicted by genes (genes + clinical covariates)		NE	32 % (47%)
↓number of dose changes		NE	Yes, however follow-up duration and indication differed across groups
↓INR monitoring frequency		Yes	Yes, however follow-up duration and indication differed across groups
Influenced time to target INR		PG attained target INR sooner⊕	No
Influenced time to stable dose		PG attained stable INR sooner⊕	No
↓ out-of-range INRs		Yes (<1.8 or >3.4)	No (<1.8 or >3.2) ⊕
↑ Time in target range		Higher in PG group ⊕	No
↓ risk of over-anticoagulation		Yes	No
↓ risk of complicationsψ		For Minor bleed, p<0.02	NE

^ФPG denotes genotype-guided therapy; STD denotes standard medical therapy

Anderson et al defined Stable dose as dose (after day 8) that was associated with ≥ 2 (within 15%) INRs in target range measured ≥ 1 week apart. Caraco et al defined stable dose as the dose associated with ≥ 2 INRs in target range, measured ≥ 1 week apart.

^⊕Primary Endpoint

NE: Not evaluated or not reported

^ψAlthough all studies defined adverse event as a composite endpoint including INR ≥4, major (and minor) hemorrhage and recurrent thromboembolic event, the cohort size and follow-up duration did not facilitate evaluation of hemorrhagic or thromboembolic complications.

^aCaraco et al ⁸⁷

^bAnderson et al ⁸⁸