Warfarin dosage adjustment strategy in Chinese population

Area of Science:

• Pharmacogenomics
• Cardiovascular Surgery
• Clinical Pharmacology

Background:

• Anticoagulation management post-heart valve replacement presents global challenges.
• Warfarin efficacy is influenced by genetic factors and drug interactions.
• Predicting safe warfarin dosage is crucial for patient outcomes.

Purpose of the Study:

• To investigate amiodarone's effect on warfarin anticoagulation.
• To determine the role of VKORC1 and CYP2C9 genotypes in warfarin dosing.
• To establish a pharmacogenetic approach for predicting safe warfarin doses.

Main Methods:

• Genotyping for VKORC1 (-1639G>A) and CYP2C9 in 271 heart valve replacement patients.
• Utilizing a multivariable regression equation to calculate warfarin dosage.
• Analyzing INR values in 80 patients across four groups based on warfarin dose and amiodarone use.

Main Results:

• High prevalence of VKORC1 AA (90%) and AG (10%) genotypes; absence of GG.
• All patients exhibited CYP2C9*1/*1 genotype; CYP2C9*1/*3 was not observed.
• Significant differences in INR values were noted between amiodarone users and non-users.
• The pharmacogenetic equation accurately predicted warfarin dosage, achieving therapeutic anticoagulation within two weeks.

Conclusions:

• Pre-operative pharmacogenetic testing for warfarin is essential for heart valve replacement patients.
• Amiodarone potentiates warfarin's anticoagulant effect, necessitating dose reduction.
• Close INR monitoring is vital when combining amiodarone and warfarin for safe and effective anticoagulation.