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Pharmacogenetic guided versus standard warfarin dosing for routine clinical care with its pharmacoeconomic impact: a randomized controlled clinical trial

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Abstract

Background

Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs).

Aim

The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies.

Methods

An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation.

Results

The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was ₹1,26,830 in the PGT arm compared to ₹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was ₹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of ₹ 71,630 well below one time GDP threshold of WTP used.

Conclusion

Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.

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Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

The study presented here is part of Ms Aishwarya Anand’s PhD work.

Funding

None.

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Authors and Affiliations

  1. Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India

    Aishwarya Anand, Naveen C Hegde, Amol N Patil, Nusrat Shafiq & Samir Malhotra

  2. Department of Cardiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Pulkit Chhabra, Jai Purohit, Ankur Gupta, Saurabh Mehrotra, Rajesh Vijayvergiya & Basant Kumar

  3. Department of Cardiothoracic and Vascular Surgery, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Rupesh Kumar

  4. Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Deepesh P Lad & Pankaj Malhotra

  5. Department of Internal Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Ritin Mohindra

  6. Department of Gastroenterology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Vishal Sharma

  7. Department of Hematology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Jasmina Ahluwalia & Reena Das

Authors
  1. Aishwarya Anand
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  2. Naveen C Hegde
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  3. Pulkit Chhabra
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  4. Jai Purohit
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  6. Ankur Gupta
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  7. Deepesh P Lad
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  10. Rajesh Vijayvergiya
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  11. Basant Kumar
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  14. Jasmina Ahluwalia
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  15. Reena Das
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  16. Amol N Patil
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  17. Nusrat Shafiq
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  18. Samir Malhotra
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Contributions

ANP and DPL designed the study. AA, NCH collected and analyzed the data. JP, PC, RK, AG, DPL, RV, BK, RM, SM, VS, and PM were involved in the patient management. JA and RD looked after the study participants’ PT/INR reporting. NS and SM supervised the study and provided critical inputs. AA, NCH and ANP wrote the first draft of the manuscript. All authors contributed to the manuscript revisions. All authors guarantee the final content of the manuscript.

Corresponding authors

Correspondence to Deepesh P Lad or Amol N Patil.

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Anand, A., Hegde, N.C., Chhabra, P. et al. Pharmacogenetic guided versus standard warfarin dosing for routine clinical care with its pharmacoeconomic impact: a randomized controlled clinical trial. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05757-1

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