What is the clinical evidence from this study?

Study design: RCT. Population: Patients requiring warfarin anticoagulation (n=191). Intervention: CYP2C9 genotype-adjusted warfarin algorithm vs. Validated algorithm ('average-dose' protocol). Primary outcome: Time within the therapeutic range (p=<0.001).

September 12, 2007

CYP2C9 Genotype-guided Warfarin Prescribing Enhances the Efficacy and Safety of Anticoagulation: A Prospective Randomized Controlled Study

Q: What are the key findings of this study?

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.

Resultado clave

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.

Diseño del estudio

Tipo

RCT (n=191)

Aleatorización

Randomized

PICO estructurado

Does CYP2C9 genotype-guided warfarin prescribing improve the efficacy and safety of anticoagulation compared to a standard algorithm in patients requiring warfarin?

Población

191 patients requiring warfarin anticoagulation (n=191)

Intervención

Warfarin dosing guided by CYP2C9 genotype-adjusted algorithms

Comparador

Warfarin dosing guided by a validated standard algorithm ('control')

Resultado

Time to first therapeutic international normalized ratio (INR) and time to stable anticoagulationsurrogate

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.

Resultado numérico

Tasa de eventos absoluta: 80.4% vs 63.4%

valor p: p=<0.001

Limitaciones

Algorithm does not incorporate other polymorphisms (VKORC1), host factors, and environmental influences

Resumen

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.

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