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CYP2C9 Genotype‐guided Warfarin Prescribing Enhances the Efficacy and Safety of Anticoagulation: A Prospective Randomized Controlled Study
Author(s) -
Caraco Y,
Blotnick S,
Muszkat M
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100316
Subject(s) - vkorc1 , warfarin , cyp2c9 , medicine , therapeutic index , clinical pharmacology , genotype , major bleeding , pharmacogenetics , pharmacology , atrial fibrillation , drug , biology , biochemistry , cytochrome p450 , metabolism , gene
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. Clinical Pharmacology & Therapeutics (2008) 83 , 3, 460–470.doi: 10.1038/sj.clpt.6100316