Acenocoumarol stabilization is delayed in CYP2C93 carriers.
OBJECTIVE
Our objective was to assess whether there is an association between the presence of allelic variants of the gene for cytochrome P450 (CYP) 2C9 and anticoagulation problems during the initial 3 to 6 months of acenocoumarol treatment.


METHODS
A prospective follow-up study was performed at 2 anticoagulation clinics in the Netherlands. Included subjects started with a standard dose regimen as follows: 6 mg on the first day, 4 mg on the second day, and 2 mg on the third day. CYP2C9 genotypes were assessed, and data on international normalized ratio (INR), comedication, and comorbidity were collected.


RESULTS
The CYP2C9 genotype of 231 subjects was assessed. Of these, 147 (63.6%) were wild-type subjects (CYP2C9*1/*1), 38 (16.5%) were carriers of CYP2C9*2, and 46 (19.9%) were carriers of CYP2C9*3. Compared with wild-type subjects, carriers of the CYP2C9*3 allele had (1) a lower chance to achieve stability in the first 6 months of therapy (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91; P <.05) and (2) an increased risk of severe overanticoagulation (INR >6.0) (hazard ratio, 3.80; 95% confidence interval, 1.54-9.39; P <.01). For both outcomes, there was no significant difference between carriers of the CYP2C9*2 allele and wild-type subjects.


CONCLUSIONS
In carriers of the CYP2C9*3 allele more difficulties in terms of stabilization and overanticoagulation were found as compared with wild-type subjects or CYP2C9*2 carriers. CYP2C9 genotyping could be useful to identify potential candidates for more frequent INR controls to minimize problems with acenocoumarol anticoagulation status.
Schalekamp
Tom
T
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht University, Utrecht, The Netherlands. t.schalekamp@pharm.uu.nl
van Geest-Daalderop
Johanna H H
JH
de Vries-Goldschmeding
Hanneke
H
Conemans
Jean
J
Bernsen Mj
M j
Mj
de Boer
Anthonius
A
D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects*; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001778:Blood Coagulation Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D017931:DNA Primers; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011446:Prospective Studies
D000925:Anticoagulants; D017931:DNA Primers; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000074:Acenocoumarol