CYP2C9 genotype-guided warfarin therapy increased time in the therapeutic range (80.4% vs 63.4%, P<0.001) and reduced minor bleeding (3.2% vs 12.5%, P<0.02) compared to a standard algorithm.
RCT (n=191)
Randomized
Does CYP2C9 genotype-guided warfarin prescribing improve the efficacy and safety of anticoagulation compared to a standard algorithm in patients requiring warfarin?
CYP2C9 genotype-guided warfarin dosing significantly reduces the time to therapeutic INR and stable anticoagulation while increasing time in therapeutic range and reducing minor bleeding compared to standard dosing.
Absolute Event Rate: 80.4% vs 63.4%
p-value: p=<0.001
Warfarin anticoagulation effect is characterized by marked variability, some of which has been attributed to CYP2C9 polymorphisms. This study prospectively examines whether a priori knowledge of CYP2C9 genotype may improve warfarin therapy. Patients were randomly assigned to receive warfarin by a validated algorithm ("control", 96 patients) or CYP2C9 genotype-adjusted algorithms ("study", 95 patients). The first therapeutic international normalized ratio and stable anticoagulation were reached 2.73 and 18.1 days earlier in the study group, respectively (P<0.001). The faster rate of initial anticoagulation was driven by a 28% higher daily dose in the study group (P<0.001). Study group patients spent more time within the therapeutic range (80.4 vs 63.4%, respectively, P<0.001) and experienced less minor bleeding (3.2 vs 12.5%, P<0.02, respectively). In conclusion, CYP2C9 genotype-guided warfarin therapy is more efficient and safer than the "average-dose" protocol. Future research should focus on construction of algorithms that incorporate other polymorphisms (VKORC1), host factors, and environmental influences.
Caraco et al. (Wed,) conducted a rct in Patients requiring warfarin anticoagulation (n=191). CYP2C9 genotype-adjusted warfarin algorithm vs. Validated algorithm ('average-dose' protocol) was evaluated on Time within the therapeutic range (p=<0.001). CYP2C9 genotype-guided warfarin therapy increased time in the therapeutic range (80.4% vs 63.4%, P<0.001) and reduced minor bleeding (3.2% vs 12.5%, P<0.02) compared to a standard algorithm.