Jonatan D Lindh1, Stefan Lundgren, Lennart Holm, Lars Alfredsson, Anders Rane. 1. Division of Clinical Pharmacology, Department of Laboratory Medicine, Institute of Environmental Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden. jonatan.lindh@ki.se
Abstract
OBJECTIVE: Our objective was to prospectively study the impact of CYP2C9 polymorphism (*2 and *3) on the risk of overanticoagulation during the induction phase of warfarin therapy. METHODS: Blood samples for genotyping were collected from 219 patients requiring warfarin therapy, and clinical data were prospectively collected during the first 3 weeks of medication. Patients were divided into 3 groups according to CYP2C9 genotype, as follows: *1 (homozygous), *2 (*1/*2 and *2/*2), and *3 (any genotype containing the *3 allele). RESULTS: During the first week of treatment, the relative risk of achieving at least 1 international normalized ratio (INR) value above the therapeutic interval (2-3) was 2.8 (95% confidence interval, 1.2-6.7) and 6.1 (2.7-13.6) in the *2 and *3 groups, respectively (with *1 used as control). During the second week, the corresponding values were 2.1 (1.2-3.7) and 3.5 (2.1-5.8), respectively. By the third week, the genetic impact was no longer evident, presumably as a result of successful dose individualization. Increased INR levels (compared with the *1 group) were already demonstrated in the *2 group on the fourth treatment day. CONCLUSIONS: The CYP2C9*2 and *3 single-nucleotide polymorphisms significantly increase the risk of overanticoagulation during the first 2 weeks of warfarin treatment, with increased INR levels evident after only 4 days' treatment in *2 carriers. Our prospective data are consistent with results from previous retrospective studies and indicate that CYP2C9 genotyping may be a means of improving safety during warfarin induction.
OBJECTIVE: Our objective was to prospectively study the impact of CYP2C9 polymorphism (*2 and *3) on the risk of overanticoagulation during the induction phase of warfarin therapy. METHODS: Blood samples for genotyping were collected from 219 patients requiring warfarin therapy, and clinical data were prospectively collected during the first 3 weeks of medication. Patients were divided into 3 groups according to CYP2C9 genotype, as follows: *1 (homozygous), *2 (*1/*2 and *2/*2), and *3 (any genotype containing the *3 allele). RESULTS: During the first week of treatment, the relative risk of achieving at least 1 international normalized ratio (INR) value above the therapeutic interval (2-3) was 2.8 (95% confidence interval, 1.2-6.7) and 6.1 (2.7-13.6) in the *2 and *3 groups, respectively (with *1 used as control). During the second week, the corresponding values were 2.1 (1.2-3.7) and 3.5 (2.1-5.8), respectively. By the third week, the genetic impact was no longer evident, presumably as a result of successful dose individualization. Increased INR levels (compared with the *1 group) were already demonstrated in the *2 group on the fourth treatment day. CONCLUSIONS: The CYP2C9*2 and *3 single-nucleotide polymorphisms significantly increase the risk of overanticoagulation during the first 2 weeks of warfarin treatment, with increased INR levels evident after only 4 days' treatment in *2 carriers. Our prospective data are consistent with results from previous retrospective studies and indicate that CYP2C9 genotyping may be a means of improving safety during warfarin induction.
Authors: Paul B Shaw; Jennifer L Donovan; Maichi T Tran; Stephenie C Lemon; Pamela Burgwinkle; Joel Gore Journal: J Thromb Thrombolysis Date: 2010-08 Impact factor: 2.300
Authors: Mia Wadelius; Leslie Y Chen; Jonatan D Lindh; Niclas Eriksson; Mohammed J R Ghori; Suzannah Bumpstead; Lennart Holm; Ralph McGinnis; Anders Rane; Panos Deloukas Journal: Blood Date: 2008-06-23 Impact factor: 22.113
Authors: A Choppin; I Irwin; L Lach; M G McDonald; A E Rettie; L Shao; C Becker; M P Palme; X Paliard; S Bowersox; D M Dennis; P Druzgala Journal: Br J Pharmacol Date: 2009-10-20 Impact factor: 8.739