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The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing

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Abstract

Background

In the Asian population, the presence of the CYP2C19 loss-of-function (LOF) allele is a known genetic variation. This allele is associated with a reduced capacity to metabolize clopidogrel into its active forms through the CYP2C19 enzyme, resulting in diminished platelet inhibition and an elevated risk of recurrent cardiovascular events. Regulatory authorities have recommended an alternative P2Y12 inhibitor, ticagrelor, for individuals carrying the LOF allele. Consequently, this study seeks to assess the impact of the CYP2C19 genotype on the Platelet reactivity index (PRI) using a rapid genetic testing approach in Asian patients with chronic coronary syndromes (CCS) who undergo percutaneous coronary intervention (PCI).

Methods

This prospective study employed a parallel design, single-center design, and randomized approach. Genotyping for the CYP2C19*2 and *3 polymorphisms was conducted using the Nested Allele-Specific Multiplex PCR (NASM-PCR) technique. Patients meeting the inclusion criteria underwent genotyping for CYP2C19 polymorphisms. Following PCI, patients were randomly assigned to receive either ticagrelor or clopidogrel. PRI assessments were performed four hours after loading dose administration. The trial was registered with ClinicalTrials.gov under the identifier NCT05516784.

Results

Among the 94 patients recruited for the study, 40 (42.55%) were identified as carriers of the LOF allele for CYP2C19*2 and *3 (*1/*2, *2/*2, *1/*3). Out of the 84 patients evaluated for PRI (44 receiving clopidogrel and 40 receiving ticagrelor), 21 (47.7%) of the clopidogrel group and 39 (97.5%) of the ticagrelor group exhibited a favorable response to antiplatelet therapy (PRI < 50). Patients treated with ticagrelor demonstrated superior antiplatelet responses compared to those receiving clopidogrel, regardless of LOF carrier status (P = 0.005 and < 0.001 for non-LOF and LOF carriers, respectively).

Conclusion

NASM-PCR as a rapid genetic test holds promise for personalizing antiplatelet therapy in Asian CCS patients.

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Data Availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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Authors and Affiliations

  1. Department of Cardiology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People’s Republic of China

    Mohammed Ahmed Akkaif

  2. School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800, Malaysia

    Mohammed Ahmed Akkaif, Nur Aizati Athirah Daud & Dzul Azri Mohamed Noor

  3. School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4YS, UK

    Abubakar Sha’aban

  4. Department of Cardiology, Penang General Hospital, Pulau Pinang, 10990, Malaysia

    Muhamad Ali SK Abdul Kader

  5. Faculty of Pharmacy, University of Malaya, Federal Territory Malaysia, Kuala Lumpur, 50603, Malaysia

    Baharudin Ibrahim

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Contributions

M.A.A., N.A.A.D., and B.I.: Conceptualization; M.A.A., N.A.A.D., D.A.M.N., M.A.S, and B.I.: Methodology; M.A.A. did the analysis, and wrote the original draft as well as the final manuscript; N.A.A.D., A.S., D.A.M.N., M.A.S, M.J.A.W., and B.I.: critically reviewed the manuscript; N.A.A.D., and B.I.: Supervision. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Mohammed Ahmed Akkaif, Nur Aizati Athirah Daud or Baharudin Ibrahim.

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The study protocol was submitted to the National Institute of Health (NIH), Ministry of Health of Malaysia, and had been reviewed and granted ethical approval by the Medical Research and Ethics Committee (MREC) (NMRR-20-2417-56795). All patients provided written informed consent for participation before study entry.

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Akkaif, M.A., Daud, N.A.A., Noor, D.A.M. et al. The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing. Cardiovasc Drugs Ther (2024). https://doi.org/10.1007/s10557-024-07544-6

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