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The need of a multicomponent guiding approach to personalize clopidogrel treatment

The Pharmacogenomics Journal volume 21, pages 116–127 (2021)Cite this article

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Abstract

Patients bearing polymorphisms termed CYP2C19 loss of function (LoF) alleles and ABCB1-C3435T may do not properly respond to standard dosage of clopidogrel and have an increased risk of thrombosis. Moreover, co-administration of proton pump inhibitors (PPIs) and clopidogrel may attenuate the antiplatelet effect. The role of pharmacogenetics and PPIs/clopidogrel drug–drug interaction has been extensively investigated in patients with acute coronary syndrome after stent implantation (ACS/PCI), while data in patients undergoing vascular surgery are scarce. Here we have performed a systematic review to evaluate the available literature in such a clinical setting and have discussed the controversies about the use of CYP2C19 pharmacogenetics and platelet function testing to personalize clopidogrel treatment. In addition, we have made a comparison of the literature data with our findings concerning patients eligible for vascular surgery and treated with clopidogrel, in whom we used a combined management based on the CYP2C19 and ABCB1 pharmacogenetic testing with monitoring of therapeutic adherence and PPIs–clopidogrel interaction. Both our data and those produced during both observational studies and randomized clinical trials confirm the validity of pharmacogenetics to personalize clopidogrel treatment and stress the importance to make a drug monitoring considering all the known variables, potentially responsible for treatment failure. However, the American Heart Association and the European Cardiovascular Society recommend against the routine use of clopidogrel pharmacogenetic testing. An update of the international guidelines on antiplatelet therapy, incorporating the evidence related to CYP2C19 pharmacogenetics and PPIs–clopidogrel drug–drug interactions is warranted both in ACS/PCI patients and subjects undergoing vascular surgery.

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Fig. 1: Shows the platelet aggregation values of the clinical cases demonstrating HTPR at T0 (before surgery).
Fig. 2: Shows clinical cases demonstrating therapeutic aggregation values at T0 (before surgery).
Fig. 3: Flow diagram of the literature screening.
Fig. 4: Grade of interaction of Proton Pump Inhibitors (PPIs) omeprazole, esomeprazole and pantoprazole on CYP2C19.

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Acknowledgements

We thank the English mother tongue Jan Festa who carefully performed the language revision of the manuscript.

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Authors and Affiliations

  1. Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno- S, Allende street, 84081, Baronissi, Salerno, Italy

    Conti Valeria, Sellitto Carmine, Manzo Valentina, Iannaccone Teresa, Costantino Maria, Torsiello Martina & Filippelli Amelia

  2. Clinical Pharmacology and Pharmacogenetics Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, via S. Leonardo 1, Salerno, Italy

    Conti Valeria & Filippelli Amelia

  3. Association non-profit F.I.R.S.Thermae (Interdisciplinary Training, Researches and spa Sciences) in Italian National Register of Research of MIUR, Via Marziale, 21, 80070, Bacoli, Naples, Italy

    Costantino Maria

  4. Vascular surgery Unit, University Hospital “San Giovanni di Dio e Ruggi D’Aragona”, Salerno- via S. Leonardo 1, Salerno, Italy

    Accarino Giancarlo & Nicolella Giovanna

  5. Department of Medicine and Health Sciences, University of Molise, Via Francesco De Sanctis, 1, 86100, Campobasso, Italy

    Corbi Graziamaria

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  1. Conti Valeria
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Valeria, C., Carmine, S., Valentina, M. et al. The need of a multicomponent guiding approach to personalize clopidogrel treatment. Pharmacogenomics J 21, 116–127 (2021). https://doi.org/10.1038/s41397-020-00189-2

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