CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study.
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
Y
Y
Clinical Pharmacology Unit, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel. caraco@hadassah.org.il
Blotnick
S
S
Muszkat
M
M
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9; D011307:Drug Prescriptions; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014859:Warfarin / Q000009:adverse effects*
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases