Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy

Mitchell K Higashi ¹, David L Veenstra , L Midori Kondo

⁰University of Washington, Department of Pharmacy, Box 357630, Health Sciences Bldg, Room H-375A, Seattle, WA 98195, USA.

Jama +

|

April 3, 2002

View abstract on PubMed

Summary

Genetic variants in CYP2C9 (cytochrome P450 2C9) increase the risk of overanticoagulation and bleeding events in patients taking warfarin. Screening for these CYP2C9 variants may help personalize warfarin dosing and reduce adverse drug reactions.

Area Of Science

Pharmacogenomics
Clinical Pharmacology
Internal Medicine

Background

Warfarin is a critical anticoagulant requiring precise management to avoid bleeding or clotting.
CYP2C9 (cytochrome P450 2C9) is the primary enzyme metabolizing warfarin.
Common CYP2C9 variants (*2 and *3) reduce enzyme activity, potentially affecting warfarin efficacy and safety.

Purpose Of The Study

To investigate the association between CYP2C9*2 and CYP2C9*3 genetic variants and the risk of overanticoagulation and bleeding in patients on warfarin therapy.

Main Methods

A retrospective cohort study was conducted at two anticoagulation clinics.
Data from 185 patients with complete warfarin exposure history were analyzed.
Outcomes included anticoagulation status (INR levels, time to stable dosing) and bleeding events.

Main Results

Patients with variant CYP2C9 alleles (*2 or *3) had a higher risk of above-range INRs (HR 1.40).
Variant genotypes required longer time to achieve stable warfarin dosing (median difference 95 days).
A significantly increased risk of serious or life-threatening bleeding events was observed in patients with variant genotypes (HR 2.39).

Conclusions

CYP2C9*2 and CYP2C9*3 polymorphisms are linked to increased risks of overanticoagulation and bleeding in warfarin users.
Genetic screening for CYP2C9 variants could inform warfarin dosing strategies and surveillance.
Personalized medicine approaches based on CYP2C9 genotype may reduce adverse drug reactions in warfarin therapy.

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