The influence of NSAIDs on coumarin sensitivity in patients with CYP2C9 polymorphism after total hip replacement surgery.
OBJECTIVE
To determine the influence of NSAIDs on the international normalized ratio (INR) in patients with cytochrome P450 (CYP)-2C9 enzyme variants starting acenocoumarol (an oral coumarin) therapy during the first 7 days after total hip replacement surgery.


METHODS
In this prospective study, an age-dependent protocol was used for the initiation of the acenocoumarol dose. Low-molecular-weight heparin was given for 5 days. The study included 100 patients undergoing total hip replacement surgery. After the inclusion of the last patient, polymerase chain reaction CYP2C9 mutation testing was performed for all patients. Drug-use evaluation of NSAIDs and other potential coumarin-drug interactions was also performed.


RESULTS
Eleven patients had an INR on 1 or more days >4.9. There were 52 patients who were using NSAIDs. Patients with a CYP2C9 mutation had a mean INR curve similar to patients without the mutation when NSAIDs were not coadministered. Within the group of patients heterozygous for a CYP2C9 mutation (n=30) only concomitant use of a NSAID resulted in an INR >4.9 (0% vs 38.9%, p<0.05).


CONCLUSIONS
In the group of patients with a CYP2C9 variant (*2 or *3 alleles), only concomitant use of a NSAID resulted in INRs >4.9. The cost effectiveness of CYP2C9 screening before elective surgery has yet to be determined.
Beinema
Maarten J
MJ
Deventer Hospital Thrombosis Center, Deventer, The Netherlands. beinemam@dz.nl
de Jong
Petra H
PH
Salden
Har J M
HJ
van Wijnen
Merel
M
van der Meer
Jan
J
Brouwers
Jacobus R B J
JR
D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000925:Anticoagulants / Q000008:administration & dosage; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019338:Polypharmacy; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000074:Acenocoumarol