Development and validation wise assessment of genotype guided warfarin dosing algorithm in Indian population

Area of Science:

• Pharmacogenomics
• Clinical Pharmacology

Background:

• Warfarin dosing is complex and influenced by genetic variations.
• Existing pharmacogenetic algorithms are often based on Western populations.

Purpose of the Study:

• To develop and validate a warfarin pharmacogenetic dose optimization algorithm tailored for the Asian population, aligning with CPIC guidelines.
• To identify key genetic and clinical factors influencing warfarin maintenance dose in Asians.

Main Methods:

• A prospective observational study involving 300 warfarin-treated patients (250 derivation, 50 validation).
• Assessment of VKORC1, CYP2C9*2, CYP2C9*3, and CYP4F2 polymorphisms.
• Collection of clinical history, sociodemographic data, and warfarin dose information.

Main Results:

• BMI, comorbidities, VKORC1, CYP2C9*2, and CYP2C9*3 significantly impacted warfarin dose (p<0.001).
• The developed algorithm showed good correlation with Gage (r=0.57) and IWPC (r=0.51) algorithms.
• High sensitivity (73%), positive predictive value (96%), and specificity (89%) were observed in the validation cohort.

Conclusions:

• The developed warfarin pharmacogenetic dose optimization algorithm is validated for the Asian population.
• The algorithm accurately categorizes patients into warfarin-sensitive, intermediate, and resistant groups.
• The algorithm is ready for clinical trial assessment.