Determinants to optimize response to clopidogrel in acute coronary syndrome

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The inhibition of platelet function by antiplatelet therapy determines the improvement of the survival of patients with clinically evident cardiovascular disease. Clopidogrel in combination with aspirin is the recommended standard of care for reducing the occurrence of cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. However, major adverse cardiovascular events including stent thrombosis occur in patients taking clopidogrel and aspirin. A growing body of evidence demonstrates that high post-treatment platelet reactivity on antiplatelet treatment is associated with increased risk of adverse clinical events. Clopidogrel requires conversion to active metabolite by cytochrome P450 isoenzymes. The active metabolite inhibits ADP-stimulated platelet activation by irreversibly binding to P2Y12 receptors. Recently, the loss-of-function CYP2C19*2 allele has been associated with decreased metabolization of clopidogrel, poor antiaggregant effect, and increased cardiovascular events. In high risk vascular patients, the CYP2C19*2 polymorphism is a strong predictor of adverse cardiovascular events and particularly of stent thrombosis. Prospective studies evaluating if an antiplatelet treatment tailored on individual characteristics of patients, CYP2C19*2 genotypes, platelet phenotype, drug-drug interaction, as well as traditional and procedural risk factors, are now urgently needed for the identification of therapeutic strategies providing the best benefit for the single subject.

Original languageEnglish
Pages (from-to)33-50
Number of pages18
JournalPharmacogenomics and Personalized Medicine
Volume3
Issue number1
Publication statusPublished - 2010

Fingerprint

clopidogrel
Acute Coronary Syndrome
Blood Platelets
Aspirin
Stents
Thrombosis
Therapeutics
Platelet Activation
Percutaneous Coronary Intervention
Standard of Care
Drug Interactions
Adenosine Diphosphate
Cytochrome P-450 Enzyme System
Isoenzymes
Blood Vessels
Cardiovascular Diseases
Alleles
Genotype
Prospective Studies
Phenotype

Keywords

  • Antiplatelet therapy
  • Clopidogrel
  • Cytochrome P450 2C19 loss-of-function polymorphism
  • Major adverse cardiovascular events
  • Percutaneous coronary interventions

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Giusti, B., Gori, A. M., Marcucci, R., Saracini, C., Vestrini, A., & Abbate, R. (2010). Determinants to optimize response to clopidogrel in acute coronary syndrome. Pharmacogenomics and Personalized Medicine, 3(1), 33-50.

Determinants to optimize response to clopidogrel in acute coronary syndrome. / Giusti, Betti; Gori, Anna Maria; Marcucci, Rossella; Saracini, Claudia; Vestrini, Anna; Abbate, Rosanna.

In: Pharmacogenomics and Personalized Medicine, Vol. 3, No. 1, 2010, p. 33-50.

Research output: Contribution to journalArticle

Giusti, B, Gori, AM, Marcucci, R, Saracini, C, Vestrini, A & Abbate, R 2010, 'Determinants to optimize response to clopidogrel in acute coronary syndrome', Pharmacogenomics and Personalized Medicine, vol. 3, no. 1, pp. 33-50.
Giusti B, Gori AM, Marcucci R, Saracini C, Vestrini A, Abbate R. Determinants to optimize response to clopidogrel in acute coronary syndrome. Pharmacogenomics and Personalized Medicine. 2010;3(1):33-50.
Giusti, Betti ; Gori, Anna Maria ; Marcucci, Rossella ; Saracini, Claudia ; Vestrini, Anna ; Abbate, Rosanna. / Determinants to optimize response to clopidogrel in acute coronary syndrome. In: Pharmacogenomics and Personalized Medicine. 2010 ; Vol. 3, No. 1. pp. 33-50.
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