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

Aishwarya Anand; Rupesh Kumar; Swati Sharma; Ankur Gupta; Rajesh Vijayvergiya; Saurabh Mehrotra; Basant Kumar; Deepesh Lad; Amol N. Patil; Nusrat Shafiq; Samir Malhotra

doi:10.1515/dmpt-2022-0189

Article

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

Aishwarya Anand , Rupesh Kumar , Swati Sharma , Ankur Gupta , Rajesh Vijayvergiya , Saurabh Mehrotra , Basant Kumar , Deepesh Lad , Amol N. Patil , Nusrat Shafiq and Samir Malhotra

Published/Copyright: April 19, 2023

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From the journal Drug Metabolism and Personalized Therapy Volume 38 Issue 3

Abstract

Objectives

A study was conducted to develop and validate the warfarin pharmacogenetic dose optimization algorithm considering the clinical pharmacogenetic implementation consortium (CPIC) recommendations for the Asian ethnicity population.

Methods

The present prospective observational study recruited warfarin-receiving patients. We collected a three ml blood sample for VKORC1, CYP2C9*2, CYP2C9*3, and CYP4F2 polymorphism assessment during the follow-up visits. Clinical history, sociodemographic and warfarin dose details were noted.

Results

The study recruited 300 patients (250 in derivation and 50 in validation timed cohort) receiving warfarin therapy. The baseline characteristics were similar in both cohorts. BMI, presence of comorbidity, VKORC1, CYP2C9*2, and CYP2C9*3 were identified as covariates significantly affecting the warfarin weekly maintenance dose (p<0.001 for all) and the same were included in warfarin pharmacogenetic dose optimization algorithm building. The algorithm built-in the present study showed a good correlation with Gage (r=0.57, p<0.0001), and IWPC (r=0.51, p<0.0001) algorithms, widely accepted in western side of the globe. The receiver operating characteristic curve analysis showed a sensitivity of 73 %, a positive predictive value of 96 %, and a specificity of 89 %. The algorithm correctly identified the validation cohort’s warfarin-sensitive, intermediate reacting, and resistant patient populations.

Conclusions

Validation and comparisons of the warfarin pharmacogenetic dose optimization algorithm have made it ready for the clinical trial assessment.

Keywords: Asian ethnicity; dose optimization algorithm; pharmacogenomic; warfarin pharmacogenetics

Corresponding author: Dr. Ankur Gupta, Associate Professor, Department of Cardiology, PGIMER, Chandigarh 160012, India, Phone: +91 9478000822, E-mail: ag_pgi@yahoo.com; and Dr. Amol N. Patil, Associate Professor, Department of Pharmacology, PGIMER, Chandigarh 160012, India, Phone: +91 9990245973, E-mail: patil.amol@pgimer.edu.in

Aishwarya Anand and Rupesh Kumar contributed equally to this work.

Acknowledgments

We would like to thank the patients who agreed to participate in this study.

Research funding: Departmental chemical grant funding was used partially for the purchase of consumables.
Author contributions: All the authors were involved in the study. ANP and DL designed the study. RK, AG, RV, SM, BK provided their own patients for the study. SM and NS guided the study. AA and SS collected the data. AA and RK, AG, ANP analyzed and interpreted the data. ANP wrote the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The Institutional Ethics Committee approved the study via letter No. INT/IEC/2021/SPL-272.
Data availability: The data are available on request from the corresponding author.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/dmpt-2022-0189).

Received: 2022-11-11

Accepted: 2023-01-13

Published Online: 2023-04-19

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Keywords for this article

Asian ethnicity; dose optimization algorithm; pharmacogenomic; warfarin pharmacogenetics