Drug and medical device interactions: Stent thrombosis and personalizing clopidogrel therapy

Betti Giusti, Anna Maria Gori, Rossella Marcucci, Claudia Saracini, Anna Vestrini, Rosanna Abbate

Research output: Contribution to journalArticle

Abstract

Antiplatelet therapy with aspirin and clopidogrel, aimed to inhibit platelet function and reactivity, is the recommended standard of care for reducing the occurrence of cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention with stent implantation. However, major adverse cardiovascular events including the severe complication of stent thrombosis occur in patients taking dual antiplatelet therapy. Clopidogrel requires intestinal absorption and hepatic conversion to active metabolite by several cytochrome P450 isoenzymes, among which the CYP2C19 plays a pivotal role; then, the active metabolite inhibits ADP-stimulated platelet activation by irreversibly binding to the P2Y12 receptor. Several factors interacting with each other are involved in determining the variability of individual response to clopidogrel. Nongenetic factors include chronic persistent factors (e.g., age, diabetes) and acute phase transient factors (e.g., inflammation). Among the numerous genetic variants investigated, recently, the loss-of-function CYP2C19*2 polymorphism has been associated with a decreased metabolization of clopidogrel, poor antiaggregant effect, and increased cardiovascular events. In high risk vascular patients, who experience percutaneous coronary intervention with stent implantation, the CYP2C19*2 polymorphism is a strong predictor of the adverse cardiovascular events and particularly stent thrombosis. Ongoing and future prospective studies evaluating if an antiplatelet treatment tailored on individual characteristics of patients genetic variants, platelet phenotype, drug-drug interactions, as well as traditional and procedural risk factors are now urgently awaited in order to define the optimal therapeutic strategies and management providing the best benefit for a given individual patient.

Original languageEnglish
Pages (from-to)124-138
Number of pages15
JournalCurrent Pharmacogenomics and Personalized Medicine
Volume8
Issue number2
Publication statusPublished - 2010

Keywords

  • Acute coronary syndromes
  • Antiplatelet therapy
  • Cytochrome P450 2C19
  • Loss-of-function polymorphism
  • Major adverse cardiovascular events
  • Stent

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Pharmacology
  • Molecular Biology
  • Genetics(clinical)

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  • Cite this

    Giusti, B., Gori, A. M., Marcucci, R., Saracini, C., Vestrini, A., & Abbate, R. (2010). Drug and medical device interactions: Stent thrombosis and personalizing clopidogrel therapy. Current Pharmacogenomics and Personalized Medicine, 8(2), 124-138.